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4130953057a25323e7e137f9d599cd5d791c212c	nice	High-intensity focused ultrasound for atrial fibrillation in association with other cardiac surgery	High-intensity focused ultrasound for atrial fibrillation in association with other cardiac surgery # Guidance Current evidence on the safety and efficacy of high-intensity focused ultrasound (HIFU) for atrial fibrillation in association with other cardiac surgery is insufficient for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake HIFU for atrial fibrillation in association with other cardiac surgery should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. In addition, use of NICE's information for the public is recommended. Audit and review clinical outcomes of all patients undergoing HIFU for atrial fibrillation in association with other cardiac surgery. Patient selection and follow-up should be carried out by a multidisciplinary team. Cardiac surgeons undertaking this procedure should have specific training in the use of high-intensity focused ultrasound equipment. Publication of safety and efficacy outcomes will be useful. NICE may review the procedure upon publication of further evidence.# The procedure # Indications Atrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It can be classified as paroxysmal, persistent or permanent. Patients with atrial fibrillation may be asymptomatic or may have symptoms such as palpitations, dizziness, breathlessness and fatigue. They have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain. Atrial fibrillation usually occurs in the absence of structural heart disease. Conservative treatments are medication to control the heart rhythm and rate, electrical cardioversion and anticoagulation to prevent the formation of blood clots. Surgery for atrial fibrillation is usually performed at the same time as open heart surgery for another indication, such as the correction of mitral-valve disease. The conventional surgical approach, including the maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative non-surgical methods of creating lesions in the atria by ablation have been developed using energy sources such as radiofrequency, microwave, cryotherapy, laser and ultrasound. # Outline of the procedure HIFU for atrial fibrillation is typically carried out in patients undergoing concomitant open heart surgery (often for mitral-valve replacement or repair). An ultrasound device is placed outside the left atrium of the beating heart and delivers focused ultrasound energy across the wall of the heart. Absorption of the ultrasound energy creates a rise in temperature, which destroys the cardiac tissue within the focal area and disrupts the transmission of the abnormal electrical impulses. # Efficacy Efficacy is based on the results of one case series of 103 patients, in which 85% (80/94) of patients were free from atrial fibrillation at 6 months' follow-up, including 80% of patients who had permanent atrial fibrillation and 100% of patients who had intermittent (paroxysmal or persistent) atrial fibrillation. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers stated that the key efficacy outcomes should include normalisation of sinus rhythm, persistence or recurrence of atrial fibrillation, atrial transport function and quality of life. # Safety This procedure is performed during open heart surgery; therefore it is difficult to differentiate the complications that relate specifically to HIFU ablation. Evidence of safety was based on the same case series of 103 patients. Early (up to 30 days after the operation) and late (more than 30 days after the operation) complications were reported in the case series, but none were considered to be related to the device or the procedure. Early complications included: bleeding that required surgical exploration in 6% (6/103) of patients; complete heart block in 4% (4/103) and sinus node dysfunction in 1% (1/103), both of which required implantation of permanent pacemakers; stroke in 3% (3/103) and serious deep wound infection in 1% (1/103). Late complications included sinus node dysfunction requiring implantation of a permanent pacemaker in 3% (3/103) of patients, multiple organ failure in 1% (1/103), delayed cardiac tamponade in 1% (1/103) and transient ischaemic attack in 1% (1/103). Mortality at 6 months' follow-up was 6% (6/103) in this case series: 4% (4/103) early deaths and 2% (2/103) late non-cardiac deaths. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers noted that theoretical adverse events include excess myocardial damage (resulting in lack of atrial transportation), damage to adjacent structures (particularly the pulmonary veins, oesophagus and phrenic nerve) and an increase in surgical risk resulting from prolonged bypass time (if bypass is required). # Other comments It was noted that technique and HIFU settings used for this procedure varied. It was also noted that it may be difficult to determine when full-thickness ablation has been achieved.# Further information NICE has issued guidance on radiofrequency ablation, microwave ablation and cryoablation for atrial fibrillation in association with other cardiac surgery. It has also issued guidance on percutaneous radiofrequency ablation for atrial fibrillation. NICE has issued a guideline on atrial fibrillation. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedure overview of high-intensity focused ultrasound ablation for atrial fibrillation as an associated procedure with other cardiac surgery, October 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of high-intensity focused ultrasound (HIFU) for atrial fibrillation in association with other cardiac surgery is insufficient for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake HIFU for atrial fibrillation in association with other cardiac surgery should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. In addition, use of NICE's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients undergoing HIFU for atrial fibrillation in association with other cardiac surgery.\n\nPatient selection and follow-up should be carried out by a multidisciplinary team. Cardiac surgeons undertaking this procedure should have specific training in the use of high-intensity focused ultrasound equipment.\n\nPublication of safety and efficacy outcomes will be useful. NICE may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nAtrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It can be classified as paroxysmal, persistent or permanent. Patients with atrial fibrillation may be asymptomatic or may have symptoms such as palpitations, dizziness, breathlessness and fatigue. They have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain.\n\nAtrial fibrillation usually occurs in the absence of structural heart disease.\n\nConservative treatments are medication to control the heart rhythm and rate, electrical cardioversion and anticoagulation to prevent the formation of blood clots. Surgery for atrial fibrillation is usually performed at the same time as open heart surgery for another indication, such as the correction of mitral-valve disease. The conventional surgical approach, including the maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative non-surgical methods of creating lesions in the atria by ablation have been developed using energy sources such as radiofrequency, microwave, cryotherapy, laser and ultrasound.\n\n# Outline of the procedure\n\nHIFU for atrial fibrillation is typically carried out in patients undergoing concomitant open heart surgery (often for mitral-valve replacement or repair). An ultrasound device is placed outside the left atrium of the beating heart and delivers focused ultrasound energy across the wall of the heart. Absorption of the ultrasound energy creates a rise in temperature, which destroys the cardiac tissue within the focal area and disrupts the transmission of the abnormal electrical impulses.\n\n# Efficacy\n\nEfficacy is based on the results of one case series of 103 patients, in which 85% (80/94) of patients were free from atrial fibrillation at 6 months' follow-up, including 80% of patients who had permanent atrial fibrillation and 100% of patients who had intermittent (paroxysmal or persistent) atrial fibrillation. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers stated that the key efficacy outcomes should include normalisation of sinus rhythm, persistence or recurrence of atrial fibrillation, atrial transport function and quality of life.\n\n# Safety\n\nThis procedure is performed during open heart surgery; therefore it is difficult to differentiate the complications that relate specifically to HIFU ablation.\n\nEvidence of safety was based on the same case series of 103 patients. Early (up to 30 days after the operation) and late (more than 30 days after the operation) complications were reported in the case series, but none were considered to be related to the device or the procedure. Early complications included: bleeding that required surgical exploration in 6% (6/103) of patients; complete heart block in 4% (4/103) and sinus node dysfunction in 1% (1/103), both of which required implantation of permanent pacemakers; stroke in 3% (3/103) and serious deep wound infection in 1% (1/103). Late complications included sinus node dysfunction requiring implantation of a permanent pacemaker in 3% (3/103) of patients, multiple organ failure in 1% (1/103), delayed cardiac tamponade in 1% (1/103) and transient ischaemic attack in 1% (1/103).\n\nMortality at 6 months' follow-up was 6% (6/103) in this case series: 4% (4/103) early deaths and 2% (2/103) late non-cardiac deaths. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers noted that theoretical adverse events include excess myocardial damage (resulting in lack of atrial transportation), damage to adjacent structures (particularly the pulmonary veins, oesophagus and phrenic nerve) and an increase in surgical risk resulting from prolonged bypass time (if bypass is required).\n\n# Other comments\n\nIt was noted that technique and HIFU settings used for this procedure varied. It was also noted that it may be difficult to determine when full-thickness ablation has been achieved.", 'Further information': 'NICE has issued guidance on radiofrequency ablation, microwave ablation and cryoablation for atrial fibrillation in association with other cardiac surgery. It has also issued guidance on percutaneous radiofrequency ablation for atrial fibrillation.\n\nNICE has issued a guideline on atrial fibrillation.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedure overview of high-intensity focused ultrasound ablation for atrial fibrillation as an associated procedure with other cardiac surgery, October 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg184
6d8f0b3cf157168f2b5c6395c0a2056041636d61	nice	Tonsillectomy using laser	Tonsillectomy using laser # Guidance Current evidence on the safety and efficacy of tonsillectomy using laser appears adequate to support the use of this technique provided that normal arrangements are in place for consent, audit and clinical governance. Use of laser for tonsillectomy may result in higher rates of haemorrhage than some other techniques, and clinicians wishing to use lasers should be specifically trained in their use. The British Association of Otorhinolaryngologists – Head and Neck Surgeons has agreed to produce standards for training. Surgeons should ensure that patients or their parents/carers understand the risk of haemorrhage after tonsillectomy using laser. In addition, use of NICE's information for the public is recommended. Surgeons should audit and review the rates of haemorrhage complicating tonsillectomy in their own practices and in the context of the techniques they use. Publication of further information about the influence of different techniques and other factors (such as age) on the incidence of haemorrhage after tonsillectomy would be useful in guiding future practice.# The procedure # Indications Indications for tonsillectomy include recurrent acute or chronic tonsillitis, peritonsillar abscess and pharyngeal obstruction/obstructive sleep apnoea. Life-threatening complications of these conditions are rare, and the main aim of surgery is to relieve symptoms. Surgical removal of the tonsils (tonsillectomy) is one of the most common surgical procedures in the UK. Traditional 'cold-steel' tonsillectomy is performed under general anaesthesia with traditional surgical instruments and ligatures to coagulate the blood vessels (haemostasis). Techniques using thermal energy that can be used in tonsillectomy for both dissection and haemostasis include diathermy (monopolar or bipolar), coblation and lasers. # Outline of the procedure A laser is used to dissect the tissue and to coagulate blood vessels. This can involve resecting the tonsillar tissue completely (laser tonsillectomy) or reducing (laser-assisted serial tonsillectomy or laser-assisted tonsil reduction) or vaporising (laser vaporisation tonsillectomy) the tissue. # Efficacy Five comparative studies assessed pain after laser dissection tonsillectomy. In four of these studies, patients treated with laser tonsillectomy reported less pain at the first postoperative assessment (usually within 24 hours) compared with those who had cold-steel dissection. At subsequent assessments, however, patients treated with laser tonsillectomy had comparatively higher pain scores until at least 2 weeks after surgery. Three studies reported on healing after laser tonsillectomy. All three studies reported that wound healing was slower after laser tonsillectomy than after cold-steel dissection. Two studies assessed outcomes following laser-assisted serial tonsillectomy. Outcomes in both studies were poorly reported. For more details, refer to the 'Sources of evidence' section. Most of the Specialist Advisers expressed no concerns about the efficacy of tonsillectomy using laser but noted that postoperative pain was often greater than with other methods. They also noted that few clinicians in the UK use lasers for tonsillectomy. # Safety Bleeding is an important complication of tonsillectomy. It can occur intraoperatively, during the first 24 hours after the operation (usually defined as primary haemorrhage) or after 24 hours (secondary haemorrhage). Postoperative haemorrhage may require re-admission to hospital and possibly further surgery. In general it was noted that intraoperative blood loss was less with the use of laser compared with cold-steel dissection. Two out of seven studies reported cases of primary haemorrhage following laser tonsillectomy. In one randomised controlled trial, 11% of patients (9/79) had a primary haemorrhage following laser tonsillectomy, compared with 6% of patients (4/72) in the cold-steel dissection group (the difference was not statistically significant). Secondary haemorrhage rates varied among the studies (range 0–19%). In a randomised controlled trial of 38 patients undergoing laser tonsillectomy on one side and cold-steel dissection on the other, 6 patients had delayed bleeding in the tonsil site resected by laser, 2 requiring re-admission. There were no incidences of secondary haemorrhage on the cold-steel-dissection side. The highest rate of secondary haemorrhage was reported in a case series, where 19% of patients (10/54) had delayed bleeding. One patient also suffered a laser burn to the tongue. These data are consistent with the National Prospective Tonsillectomy Audit, which found that the lowest rates of secondary haemorrhage (requiring or not requiring further operation) were associated with cold-steel dissection with suture haemostasis, with higher rates reported with the use of other thermal techniques. In two studies (86 and 66 patients), no peri-operative or anaesthesia-related complications, or early or delayed bleeding, were reported following laser-assisted serial tonsillectomy. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers considered that there was a slight increase in the risk of postoperative haemorrhage with laser tonsillectomy compared with cold-steel dissection. They also noted the risk of laser damage to the patient's face and heat damage to the upper airway. # Other comments It was noted that a number of different types of laser can be used. It was also noted that the National Prospective Tonsillectomy Audit recommended that all surgeons undertaking tonsillectomy should be trained in the use of cold-steel dissection and ligature haemostasis, as well as electrosurgical techniques.# Further information NICE has issued guidance on electrosurgery (diathermy and coblation) for tonsillectomy and tonsillectomy using ultrasonic scalpel. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedure overview of tonsillectomy using laser, December 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of tonsillectomy using laser appears adequate to support the use of this technique provided that normal arrangements are in place for consent, audit and clinical governance.\n\nUse of laser for tonsillectomy may result in higher rates of haemorrhage than some other techniques, and clinicians wishing to use lasers should be specifically trained in their use. The British Association of Otorhinolaryngologists – Head and Neck Surgeons has agreed to produce standards for training.\n\nSurgeons should ensure that patients or their parents/carers understand the risk of haemorrhage after tonsillectomy using laser. In addition, use of NICE's information for the public is recommended.\n\nSurgeons should audit and review the rates of haemorrhage complicating tonsillectomy in their own practices and in the context of the techniques they use. Publication of further information about the influence of different techniques and other factors (such as age) on the incidence of haemorrhage after tonsillectomy would be useful in guiding future practice.", 'The procedure': "# Indications\n\nIndications for tonsillectomy include recurrent acute or chronic tonsillitis, peritonsillar abscess and pharyngeal obstruction/obstructive sleep apnoea. Life-threatening complications of these conditions are rare, and the main aim of surgery is to relieve symptoms.\n\nSurgical removal of the tonsils (tonsillectomy) is one of the most common surgical procedures in the UK. Traditional 'cold-steel' tonsillectomy is performed under general anaesthesia with traditional surgical instruments and ligatures to coagulate the blood vessels (haemostasis). Techniques using thermal energy that can be used in tonsillectomy for both dissection and haemostasis include diathermy (monopolar or bipolar), coblation and lasers.\n\n# Outline of the procedure\n\nA laser is used to dissect the tissue and to coagulate blood vessels. This can involve resecting the tonsillar tissue completely (laser tonsillectomy) or reducing (laser-assisted serial tonsillectomy or laser-assisted tonsil reduction) or vaporising (laser vaporisation tonsillectomy) the tissue.\n\n# Efficacy\n\nFive comparative studies assessed pain after laser dissection tonsillectomy. In four of these studies, patients treated with laser tonsillectomy reported less pain at the first postoperative assessment (usually within 24 hours) compared with those who had cold-steel dissection. At subsequent assessments, however, patients treated with laser tonsillectomy had comparatively higher pain scores until at least 2 weeks after surgery.\n\nThree studies reported on healing after laser tonsillectomy. All three studies reported that wound healing was slower after laser tonsillectomy than after cold-steel dissection.\n\nTwo studies assessed outcomes following laser-assisted serial tonsillectomy. Outcomes in both studies were poorly reported. For more details, refer to the 'Sources of evidence' section.\n\nMost of the Specialist Advisers expressed no concerns about the efficacy of tonsillectomy using laser but noted that postoperative pain was often greater than with other methods. They also noted that few clinicians in the UK use lasers for tonsillectomy.\n\n# Safety\n\nBleeding is an important complication of tonsillectomy. It can occur intraoperatively, during the first 24 hours after the operation (usually defined as primary haemorrhage) or after 24 hours (secondary haemorrhage). Postoperative haemorrhage may require re-admission to hospital and possibly further surgery.\n\nIn general it was noted that intraoperative blood loss was less with the use of laser compared with cold-steel dissection. Two out of seven studies reported cases of primary haemorrhage following laser tonsillectomy. In one randomised controlled trial, 11% of patients (9/79) had a primary haemorrhage following laser tonsillectomy, compared with 6% of patients (4/72) in the cold-steel dissection group (the difference was not statistically significant).\n\nSecondary haemorrhage rates varied among the studies (range 0–19%). In a randomised controlled trial of 38 patients undergoing laser tonsillectomy on one side and cold-steel dissection on the other, 6 patients had delayed bleeding in the tonsil site resected by laser, 2 requiring re-admission. There were no incidences of secondary haemorrhage on the cold-steel-dissection side. The highest rate of secondary haemorrhage was reported in a case series, where 19% of patients (10/54) had delayed bleeding. One patient also suffered a laser burn to the tongue.\n\nThese data are consistent with the National Prospective Tonsillectomy Audit, which found that the lowest rates of secondary haemorrhage (requiring or not requiring further operation) were associated with cold-steel dissection with suture haemostasis, with higher rates reported with the use of other thermal techniques.\n\nIn two studies (86 and 66 patients), no peri-operative or anaesthesia-related complications, or early or delayed bleeding, were reported following laser-assisted serial tonsillectomy. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers considered that there was a slight increase in the risk of postoperative haemorrhage with laser tonsillectomy compared with cold-steel dissection. They also noted the risk of laser damage to the patient's face and heat damage to the upper airway.\n\n# Other comments\n\nIt was noted that a number of different types of laser can be used.\n\nIt was also noted that the National Prospective Tonsillectomy Audit recommended that all surgeons undertaking tonsillectomy should be trained in the use of cold-steel dissection and ligature haemostasis, as well as electrosurgical techniques.", 'Further information': 'NICE has issued guidance on electrosurgery (diathermy and coblation) for tonsillectomy and tonsillectomy using ultrasonic scalpel.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedure overview of tonsillectomy using laser, December 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg186
d26b1c359d7defa0080baef1883fb20a50e1a260	nice	Catheterless oesophageal pH monitoring	Catheterless oesophageal pH monitoring # Guidance Current evidence on the safety and efficacy of catheterless oesophageal pH monitoring appears adequate to support the use of this technique provided that normal arrangements are in place for consent, audit and clinical governance.# The procedure # Indications Gastro-oesophageal reflux disease (GORD) is a common disorder in which a backwash of gastric juices into the oesophagus leads to inflammation and pain. Symptoms include heartburn, belching and regurgitation of gastric contents. Complications of GORD include oesophageal stricture and Barrett's oesophagus (which is associated with carcinoma of the oesophagus). The frequency of exposure to gastric acid over a given period provides a measure of the severity of the disease and can be measured by oesophageal pH monitoring. Common indications for pH monitoring include symptoms that are refractory to therapy with proton pump inhibitors, evaluation before surgery and recurrence of symptoms after anti-reflux surgery. Ambulatory oesophageal pH monitoring is commonly undertaken by transnasal placement of a pH probe on a catheter. However, this can cause nasal and pharyngeal discomfort, which may cause the patient to alter their diet and activity, potentially giving misleading results. Catheterless oesophageal pH monitoring is suitable for patients who do not tolerate nasal intubation. # Outline of the procedure A catheterless pH monitoring system comprises a plastic capsule that houses a pH sensor and a transmitter. After endoscopy, the capsule is inserted into the oesophagus and is attached at a chosen site on the oesophageal wall by a vacuum that draws the oesophageal mucosa into a well on the side of the capsule. A spring-loaded pin is then released across the well, tangential to the axis of the oesophagus, to fix the capsule in place. Correct placement and attachment of the capsule is confirmed endoscopically. The capsule continuously monitors oesophageal pH and transmits the data every few seconds to a small receiver worn by the patient. After a few days, the capsule detaches from the oesophageal wall and passes through the digestive tract. # Efficacy During a randomised controlled study (n = 50), the frequency of GORD symptoms was similar during catheterless and catheter-based monitoring. Overall quality-of-life scores based on the short-form SF-36 scale were also similar between the groups. Significantly more patients who underwent the catheterless monitoring (88%) than the catheter-based monitoring (48%) were willing to have a repeat test if necessary (p = 0.005). In a within-patient study of 33 patients who had both catheterless and catheter-based monitoring simultaneously, a total of 1388 reflux episodes were recorded over a 24-hour period. Of these reflux episodes, 41% (563/1388) were recorded by both devices, 52% (724/1388) were recorded only by the catheter-based system and 7% (101/1388) only by the catheterless monitor. Overall the concordance of reflux episodes was 88% (Kappa statistic 0.76). A non-randomised controlled study in healthy volunteers found that, after calibration, the catheterless monitor identified significantly fewer reflux episodes (mean 37.9) during 24-hour monitoring than a catheter-based system (mean 69.8) (p < 0.05). Whether these findings relate to asymptomatic reflux in healthy volunteers or previously undetected disease is unclear. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers noted that catheterless oesophageal pH monitoring may provide accurate recording under conditions of normal daily activity. # Safety Follow-up across all the studies included in the overview is based solely on the period of monitoring used; no longer-term data are available. Among patients in a case series and in the catheterless monitoring arms of controlled studies, the incidences of chest pain reported were 5% (4/85), 33% (26/80) and 36% (9/25). In one of these studies, 2% (2/85) of patients requested immediate removal of the capsule after the 48-hour monitoring period because of chest pain. In a randomised controlled trial, the incidence of chest pain was higher with a catheterless monitor (60%) compared with a catheter-based system (24%) (p = 0.01). However, fewer patients reported difficulty swallowing (36%) with the catheterless system than with the catheter-based approach (68%) (p = 0.024). In the same study, significantly fewer patients with the catheterless monitoring had nose pain, runny nose, throat pain, throat discomfort or headache. Also, among patients in employment, 58% of the patients with a catheterless capsule were able to return to work during monitoring, compared with 11% of those with the catheter-based system (p = 0.049). In a study of 44 children aged 6–19 years who had catheterless oesophageal pH monitoring, 95% (36/38) of parents were willing to allow their child to undergo further catheterless monitoring. In this study, the 12 patients who had previously had nasal catheter monitoring were reported to prefer the catheterless method. There were no reports in the reviewed literature of adverse events relating to the endoscopic component of the procedure. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers reported that adverse events included chest discomfort, mucosal tear, failure of the capsule to detach and failure of data retrieval. They also noted that additional theoretical complications included haemorrhage, oesophageal perforation, oesophageal ulceration, capsule misplacement and failure to pass the capsule once detached. # Other comments It was noted that this procedure would be particularly appropriate in children and other patients who may not tolerate the nasal intubation required for catheter-based monitoring. It was also noted that this procedure may be unsuitable for some patients, for example patients with pacemakers.# Further information The Institute has issued a clinical guideline on managing dyspepsia in adults in primary care. Andrew DillonChief ExecutiveJuly 2006 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of catheterless oesophageal pH monitoring', January 2006. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of catheterless oesophageal pH monitoring appears adequate to support the use of this technique provided that normal arrangements are in place for consent, audit and clinical governance.', 'The procedure': "# Indications\n\nGastro-oesophageal reflux disease (GORD) is a common disorder in which a backwash of gastric juices into the oesophagus leads to inflammation and pain. Symptoms include heartburn, belching and regurgitation of gastric contents. Complications of GORD include oesophageal stricture and Barrett's oesophagus (which is associated with carcinoma of the oesophagus). The frequency of exposure to gastric acid over a given period provides a measure of the severity of the disease and can be measured by oesophageal pH monitoring. Common indications for pH monitoring include symptoms that are refractory to therapy with proton pump inhibitors, evaluation before surgery and recurrence of symptoms after anti-reflux surgery.\n\nAmbulatory oesophageal pH monitoring is commonly undertaken by transnasal placement of a pH probe on a catheter. However, this can cause nasal and pharyngeal discomfort, which may cause the patient to alter their diet and activity, potentially giving misleading results. Catheterless oesophageal pH monitoring is suitable for patients who do not tolerate nasal intubation.\n\n# Outline of the procedure\n\nA catheterless pH monitoring system comprises a plastic capsule that houses a pH sensor and a transmitter. After endoscopy, the capsule is inserted into the oesophagus and is attached at a chosen site on the oesophageal wall by a vacuum that draws the oesophageal mucosa into a well on the side of the capsule. A spring-loaded pin is then released across the well, tangential to the axis of the oesophagus, to fix the capsule in place. Correct placement and attachment of the capsule is confirmed endoscopically. The capsule continuously monitors oesophageal pH and transmits the data every few seconds to a small receiver worn by the patient. After a few days, the capsule detaches from the oesophageal wall and passes through the digestive tract.\n\n# Efficacy\n\nDuring a randomised controlled study (n = 50), the frequency of GORD symptoms was similar during catheterless and catheter-based monitoring. Overall quality-of-life scores based on the short-form SF-36 scale were also similar between the groups. Significantly more patients who underwent the catheterless monitoring (88%) than the catheter-based monitoring (48%) were willing to have a repeat test if necessary (p = 0.005).\n\nIn a within-patient study of 33 patients who had both catheterless and catheter-based monitoring simultaneously, a total of 1388 reflux episodes were recorded over a 24-hour period. Of these reflux episodes, 41% (563/1388) were recorded by both devices, 52% (724/1388) were recorded only by the catheter-based system and 7% (101/1388) only by the catheterless monitor. Overall the concordance of reflux episodes was 88% (Kappa statistic 0.76).\n\nA non-randomised controlled study in healthy volunteers found that, after calibration, the catheterless monitor identified significantly fewer reflux episodes (mean 37.9) during 24-hour monitoring than a catheter-based system (mean 69.8) (p < 0.05). Whether these findings relate to asymptomatic reflux in healthy volunteers or previously undetected disease is unclear. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers noted that catheterless oesophageal pH monitoring may provide accurate recording under conditions of normal daily activity.\n\n# Safety\n\nFollow-up across all the studies included in the overview is based solely on the period of monitoring used; no longer-term data are available.\n\nAmong patients in a case series and in the catheterless monitoring arms of controlled studies, the incidences of chest pain reported were 5% (4/85), 33% (26/80) and 36% (9/25). In one of these studies, 2% (2/85) of patients requested immediate removal of the capsule after the 48-hour monitoring period because of chest pain.\n\nIn a randomised controlled trial, the incidence of chest pain was higher with a catheterless monitor (60%) compared with a catheter-based system (24%) (p = 0.01). However, fewer patients reported difficulty swallowing (36%) with the catheterless system than with the catheter-based approach (68%) (p = 0.024). In the same study, significantly fewer patients with the catheterless monitoring had nose pain, runny nose, throat pain, throat discomfort or headache. Also, among patients in employment, 58% of the patients with a catheterless capsule were able to return to work during monitoring, compared with 11% of those with the catheter-based system (p = 0.049).\n\nIn a study of 44 children aged 6–19 years who had catheterless oesophageal pH monitoring, 95% (36/38) of parents were willing to allow their child to undergo further catheterless monitoring. In this study, the 12 patients who had previously had nasal catheter monitoring were reported to prefer the catheterless method.\n\nThere were no reports in the reviewed literature of adverse events relating to the endoscopic component of the procedure. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers reported that adverse events included chest discomfort, mucosal tear, failure of the capsule to detach and failure of data retrieval. They also noted that additional theoretical complications included haemorrhage, oesophageal perforation, oesophageal ulceration, capsule misplacement and failure to pass the capsule once detached.\n\n# Other comments\n\nIt was noted that this procedure would be particularly appropriate in children and other patients who may not tolerate the nasal intubation required for catheter-based monitoring.\n\nIt was also noted that this procedure may be unsuitable for some patients, for example patients with pacemakers.", 'Further information': "The Institute has issued a clinical guideline on managing dyspepsia in adults in primary care.\n\nAndrew DillonChief ExecutiveJuly 2006\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of catheterless oesophageal pH monitoring', January 2006.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg187
8540de7916b91c9df76db30c55a39c8b33eb4c88	nice	Docetaxel for the treatment of hormone-refractory metastatic prostate cancer	Docetaxel for the treatment of hormone-refractory metastatic prostate cancer Evidence-based recommendations on docetaxel for treating hormone-refractory metastatic prostate cancer in adults. # Guidance Docetaxel is recommended, within its licensed indications, as a treatment option for men with hormone-refractory metastatic prostate cancer only if their Karnofsky performance-status score is 60% or more. It is recommended that treatment with docetaxel should be stopped: at the completion of planned treatment of up to 10 cycles, or if severe adverse events occur, or in the presence of progression of disease as evidenced by clinical or laboratory criteria, or by imaging studies. Repeat cycles of treatment with docetaxel are not recommended if the disease recurs after completion of the planned course of chemotherapy.# Clinical need and practice The prostate gland is present only in men. It is located just below the bladder exit, surrounding the urethra, and is subdivided into three zones: central, transition and peripheral. The peripheral zone, at the back of the prostate, is the part most susceptible to prostate cancer. The extent of prostate cancer is classified into stages I–IV. At stages I and II the disease is confined to the prostate. At stage III the tumour is more locally advanced and at stage IV either it is locally advanced and invading local adjacent structures, or it has associated distant metastases. The growth of most prostate cancers is stimulated by testosterone, and hormonal therapies that modify levels of, or responses to, testosterone are standard treatment for men with metastatic disease. Hormonal therapies are initially effective in 80% of men with metastatic prostate cancer, but after around 18 months the disease usually becomes unresponsive to hormone treatment and will progress. Hormone-refractory metastatic prostate cancer is defined on the basis of biochemical testing (prostate-specific antigen, PSA), findings of imaging studies, or using clinical criteria of progressive metastatic disease despite castrate serum levels of testosterone. Data on the epidemiology of hormone-refractory metastatic prostate cancer are limited; therefore inferences must be drawn from available data for prostate cancer. In the UK, prostate cancer is the most common male cancer, excluding non-melanoma skin cancer. In 2001 there were 26,067 new cases in England and 1746 in Wales, giving age-standardised incidence rates of 89.8 and 92.6 per 100,000 men respectively. Prostate cancer is the second most common cause of male cancer deaths, accounting for 13% of them. In 2003 there were 8582 deaths in England and 579 in Wales from prostate cancer, giving age-standardised mortality rates of 27.3 and 28.6 per 100,000 men respectively. It has been estimated that most of the deaths are in patients with hormone-refractory metastatic prostate cancer. Prostate cancer is associated with substantial morbidity that can have a significant impact on the patients, and on their families and carers. Prostate cancer was responsible for almost 40,000 hospital episodes in the 2003–04 financial year, although it is unknown how many of these related to patients with hormone-refractory metastatic prostate cancer. The symptoms of hormone-refractory metastatic prostate cancer may be related to compression of the urethra, metastases to bone and other sites, and adverse effects of treatment. Urinary symptoms include difficulty starting the flow of urine, passing urine more often, and discomfort while passing urine. More than 90% of patients with late-stage prostate cancer develop metastases to bone, and this can cause debilitating and sometimes uncontrollable pain, pathological fractures and spinal cord compression. Patients may receive surgery, radiotherapy, steroids and analgesics as well as hormonal treatment and chemotherapy, and they may suffer adverse effects related to all of these. The primary risk factor for prostate cancer is increasing age: 90% of cases are in men older than 60, and 42% in men older than 75. Worldwide, the highest rates are observed in African-American men, with much lower rates seen in men of Asian origin. The cause of prostate cancer is probably multifactorial, involving environmental and genetic factors. Prostate cancer does not occur in castrated men, so testosterone is implicated. High levels of insulin-like growth factor (IGF-1), a protein involved in cell metabolism, may also be involved. About 9% of cases are thought to have a genetic component. Diets high in animal fats and dairy products appear to be associated with increased risk of prostate cancer. The prognosis is poor for patients with hormone-refractory metastatic prostate cancer: survival is not expected to exceed between 9 and 12 months. Hormone-refractory metastatic prostate cancer cannot be cured. The aim of treatment is to improve symptoms, prolong life and slow progression of the disease. There is no gold standard treatment for hormone-refractory metastatic prostate cancer in the UK. Clinical management is acknowledged to be multimodal rather than sequential and patients may receive a combination of palliative treatments. Treatment options include second-line hormonal therapy, chemotherapy with or without corticosteroids, and best supportive care. The choice of therapy depends on the symptoms, the site of relapse, the performance status (see appendix D) of the patient and the presence of other comorbidities. Best supportive care can be provided with radiotherapy, bisphosphonates, steroids and analgesics, and is the only option for patients who are too ill to tolerate further active intervention. Tolerability of chemotherapy is of concern, particularly because most patients with prostate cancer are elderly and many have other medical problems. Chemotherapy regimens that have been used to treat the cancer include those based on mitoxantrone, estramustine and taxanes such as docetaxel. Mitoxantrone is widely used in the UK for hormone-refractory metastatic prostate cancer patients who are fit for chemotherapy, even though it is not licensed for this indication. The Institute has been informed by several consultees that a combination of mitoxantrone and prednisolone has come to be accepted as the standard care for this group of patients. NICE's cancer service guidance 'Improving outcomes in urological cancers' states that chemotherapy should be considered for men with symptomatic hormone-refractory prostate cancer, trials of chemotherapy should be supported, and that palliative radiotherapy should also be available. There are a number of guidelines produced by professional organisations.# The technology Docetaxel (Sanofi-Aventis) is an anti-neoplastic drug that belongs to a class of drugs known as taxanes. It works by disrupting the microtubular network that is essential for mitotic and interphase cellular functions, causing inhibition of cell division and cell death. Docetaxel is licensed for use in combination with prednisone or prednisolone for the treatment of patients with hormone-refractory metastatic prostate cancer. Docetaxel is administered as a 1-hour infusion once every 3 weeks. The recommended dose is 75 mg/m2, with twice daily oral administration of prednisone or prednisolone at a dose of 5 mg. Reported adverse effects of docetaxel include hypersensitivity reactions (presenting as flushing, skin reactions, hypotension and bronchospasm), bone marrow suppression (neutropenia, thrombocytopenia, anaemia), cutaneous reactions, fluid retention, peripheral neuropathy, alopecia, cardiac disorders and tiredness. Contraindications include severe allergic reaction, low white blood cell count due to bone-marrow damage (myelosuppression), or severe liver disease. Premedication with a corticosteroid is usually recommended to help prevent allergic reaction. For full details of side effects and contraindications, see the summary of product characteristics. The net price of docetaxel (40 mg/ml) is £162.75 for a 0.5 ml vial and £534.75 for a 2 ml vial (excluding VAT; 'British national formulary', 50th edition). The cost per patient, assuming an average of seven cycles of treatment, would be approximately £8000. Costs may vary in different settings because of negotiated procurement discounts.# Evidence and interpretation The Appraisal Committee (appendix A) considered evidence from a number of sources (appendix B). # Clinical effectiveness One randomised controlled trial (RCT) that investigated docetaxel within its licensed indications was identified (TAX327). In TAX327, docetaxel plus prednisone or prednisolone was compared with mitoxantrone plus prednisone or prednisolone. TAX327 was an international, multicentre, open-label, phase III RCT. The trial enrolled 1006 men with metastatic prostate cancer with disease progression during hormonal therapy. The men were randomised to three chemotherapy arms, all of which received prednisone or prednisolone 5 mg orally twice daily. The chemotherapy regimens were: docetaxel at 75 mg/m2 administered every 3 weeks (335 patients); docetaxel at 30 mg/m2 administered weekly for the first 5 weeks in a 6-week cycle (334 patients); and mitoxantrone 12 mg/m2 administered every 3 weeks (337 patients). Up to 10 cycles of treatment were planned for the 3-weekly docetaxel group and the mitoxantrone group, and up to five cycles (of 6 weeks each) in the weekly docetaxel group. Patients in the docetaxel groups also received premedication with dexamethasone. Patients were required to have a Karnofsky performance-status score (see appendix D) of at least 60%, and stable levels of pain for at least 7 days before randomisation. The median length of follow-up was 20.8 months for the 3-weekly docetaxel group and 20.7 months for the other two groups. The planned treatment was delivered to 98% of patients in the 3-weekly docetaxel group, 96% of patients in the weekly docetaxel group and 99% in the mitoxantrone group. There was a high level of crossover between groups; 27% of patients randomised to the 3‑weekly docetaxel group received mitoxantrone and 20% of patients randomised to the mitoxantrone group received docetaxel. Overall survival was the primary end point for the trial and was defined as the time from the date of randomisation to the date of death from any cause, or censored at the date of last contact. There was a statistically significant benefit in terms of overall survival for the 3-weekly docetaxel group compared with the mitoxantrone group, with a hazard ratio for death of 0.76 (95% confidence interval 0.62 to 0.94, p = 0.009). At the time of analysis 166/335 (50%) patients receiving 3-weekly docetaxel and 201/337 (60%) of patients receiving mitoxantrone had died. The median survival was 18.9 months (95% CI 17.0 to 21.2) in the 3-weekly docetaxel group compared with 16.5 months (95% CI 14.4 to 18.6) in the mitoxantrone group. There was no statistically significant difference in overall survival between the weekly docetaxel group and the mitoxantrone group, with a hazard ratio for death of 0.91 (95% CI 0.75 to 1.11). Quality of life response was defined as a 16-point improvement in score on the Functional Assessment of Cancer Therapy – Prostate (FACT-P) questionnaire, compared with baseline, on two measures at least 3 weeks apart. There was a statistically significant benefit in terms of quality of life response observed for both the 3-weekly docetaxel group (22% response; 95% CI 17 to 27%) and the weekly docetaxel group (23% response; 95% CI 18 to 28%) compared with the mitoxantrone group (13% response; 95% CI 9 to 18%), giving a relative risk of 1.67 (95% CI 1.14 to 2.45, p = 0.009) for the 3-weekly docetaxel group, and 1.75 (95% CI 1.20 to 2.56, p= 0.005) for the weekly docetaxel group. The responses to the FACT-P questionnaire were not mapped to utility values. In TAX327 there was a statistically significant benefit in terms of pain response observed for the 3-weekly docetaxel group (35% response; 95% CI 27 to 43%) compared with the mitoxantrone group (22% response, 95% CI 16 to 29%), giving a relative risk of 1.58 (95% CI 1.1 to 2.27). In TAX327 a statistically significant benefit in terms of PSA response was observed for the 3-weekly docetaxel group (45% response; 95% CI 40 to 51%) compared with the mitoxantrone group (32% response; 95% CI 26 to 37%), giving a relative risk of 1.41 (95% CI 1.14 to 1.73). In TAX327 a higher proportion of grade 3 or 4 adverse events was reported in the 3-weekly docetaxel group (45.8%) than in the mitoxantrone group (34.6%). Adverse events were measured using the Common Toxicity Criteria of the US National Cancer Institute, version 2, and were reported for all 997 patients who received their planned treatment. To allow for a comparison between docetaxel and relevant comparators other than mitoxantrone plus corticosteroid (for example, other chemotherapy regimens and best supportive care), the Assessment Group searched for RCTs in which other treatments were compared with mitoxantrone plus a corticosteroid, which could then be used as the common comparator. The Assessment Group performed a meta-analysis of the results from three RCTs comparing mitoxantrone plus a corticosteroid with corticosteroid alone. Although various health outcomes other than mortality were measured in those studies (including health-related quality of life and pain response in two of them), the only outcome suitable for the pooling of results was overall survival. The pooled estimate of the hazard ratio for death for mitoxantrone plus corticosteroid versus corticosteroid was 0.99 (95% CI 0.82 to 1.20). This was then compared indirectly, using appropriate statistical analysis, with that from the TAX327 study, giving an indirect hazard ratio for death for docetaxel plus a corticosteroid (prednisone or prednisolone) versus corticosteroid alone (prednisone, prednisolone or hydrocortisone), of 0.752 (95% CI 0.567 to 0.999). The Assessment Report notes that results of the adjusted indirect comparison should be interpreted with caution because the underlying trials differed in patient population and methodology. Two other RCTs that investigated the effects of docetaxel in combination with estramustine in patients with hormone-refractory metastatic prostate cancer were submitted in support of the efficacy of docetaxel and included in the Assessment Report. SWOG 9916 compared docetaxel plus estramustine versus mitoxantrone plus prednisone. A statistically significant benefit, in terms of overall survival, was observed for the docetaxel plus estramustine group compared with the mitoxantrone plus prednisone group, with a hazard ratio for death of 0.80 (95% CI 0.67 to 0.97). Oudard and coworkers investigated two different regimens of docetaxel plus prednisone plus estramustine versus mitoxantrone plus prednisone. There was a non-statistically significant reduction in the relative risk of death for patients in the docetaxel groups. The median survival was longer in the docetaxel groups than in the mitoxantrone group, but the difference was not statistically significant. # Cost effectiveness The manufacturer (Sanofi-Aventis) and the Assessment Group provided estimates of cost effectiveness. Some consultees commented on economic issues. The Assessment Group developed its own economic model and critiqued the model submitted by Sanofi-Aventis. The Assessment Group's literature search did not yield any suitable cost-effectiveness studies of docetaxel-based treatment regimens. One study was found that compared mitoxantrone and prednisone with prednisone alone and was based on the CCI-NOV-22 RCT. That study was used to inform the follow-up costs of the Assessment Group's economic model. ## Summary of evidence of cost effectiveness from the manufacturer The Sanofi-Aventis model estimates the incremental cost per life-year gained (LYG) from docetaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone. No adjustment is made for quality of life. The evaluation is based on an analysis of patient-level data derived from prospective collection of resource use and patient outcome data from the TAX327 trial. Only the 3-weekly regimen of docetaxel is considered in the analysis, in keeping with the licensed recommended dose. Two analyses are presented: the preliminary analysis uses the difference in median survival within the TAX327 trial as the measure of clinical benefit, and the base case uses an estimate of the mean difference in survival extrapolated beyond the trial period; data extrapolation is used to characterise the survival of patients beyond the period of follow-up in the trial. The sponsor submission states that in economic valuation, mean survival times are preferred to medians to provide the best estimate of relative cost effectiveness between two competing interventions. Uncertainty is considered using two different one-way sensitivity analyses, one related to the estimate of survival, and the other to that of costs per patient. The base-case result of the Sanofi-Aventis model was £19,483 as the incremental cost per life year gained from docetaxel plus prednisone or prednisolone over mitoxantrone plus prednisone or prednisolone. In the preliminary analysis, the incremental cost per life year gained was £30,280. ## Summary of economic evaluation undertaken by the Assessment Group The Assessment Group model estimates the incremental cost per quality-adjusted life year (QALY) gained by using docetaxel plus prednisone or prednisolone compared with the least expensive of a number of treatment comparators not excluded by dominance or extended dominance. It is a probabilistic model that was run for a time horizon of 15 years. A Markov model was used to estimate mean survival and incorporate discounting. Resource utilisation and cost data were estimated from the perspective of the NHS, based on the drug acquisition and administration costs for each intervention and subsequent follow-up costs including the management of side effects, further chemotherapies and palliative care. The Assessment Group undertook a systematic review of literature on measurement of the utility associated with the health-related quality of life of patients with hormone-refractory metastatic prostate cancer, and used this review to inform inputs to the model. Two analyses were reported. Analysis 1 compares 3-weekly docetaxel plus prednisone or prednisolone, mitoxantrone plus prednisone or prednisolone, and best supportive care in the form of prednisone or prednisolone alone. Analysis 2 extends this comparison to include the full range of potential comparators identified in the clinical effectiveness review. In both base cases, and all reported sensitivity analyses, the relevant resulting incremental cost-effectiveness ratio (ICER) is that of 3-weekly docetaxel plus prednisone or prednisolone (the licensed regimen) compared with mitoxantrone plus prednisone or prednisolone (the cheapest non-dominated strategy). Uncertainty is characterised using probabilistic sensitivity analysis, as well as three different one-way sensitivity analyses. In the base-case results of the Assessment Group model the ICER of 3-weekly docetaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone is estimated to be £32,700 per QALY, with all other strategies compared in both analyses dominated by mitoxantrone plus prednisone or prednisolone. Three one-way sensitivity analyses were undertaken to test the robustness of the model to alternative assumptions about discount rates, utility associated with health-related quality of life and the impact of adverse effects on quality of life. The ICER associated with 3-weekly docetaxel plus prednisone or prednisolone remained fairly robust to these variations, with estimates ranging from £28,000 to £33,000 per QALY. # Consideration of the evidence The Committee reviewed the data available on the clinical and cost effectiveness of docetaxel for hormone-refractory metastatic prostate cancer, having considered evidence on the nature of the condition and the value placed on the benefits of docetaxel by people with hormone-refractory metastatic prostate cancer, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources. The Committee noted that prednisone was used as an alternative to prednisolone in the RCTs. It was aware that prednisone is a pro-drug of prednisolone, and that in the UK prednisolone has historically been preferred to prednisone on the grounds that it does not require conversion to the active substance. The Committee concluded that in practice the difference between prednisone and prednisolone was not clinically significant, and it therefore accepted the relevance of the results of international studies to the appraisal. The Committee understood from the testimony of the clinical experts that docetaxel is the first treatment to show survival benefit in men with hormone-refractory metastatic prostate cancer. The Committee was persuaded that there was a significant survival advantage for the 3-weekly docetaxel regimen over treatment with mitoxantrone, as opposed to the weekly regimen, for which there was no statistically significant difference. It also considered that this differential effect between the two docetaxel regimens was biologically plausible. The Committee considered evidence from the SWOG 9916 trial and noted that although the regimen was not licensed, its results added weight to the evidence of the effect on overall survival of a 3-weekly regimen of docetaxel compared with treatment with mitoxantrone. The Committee carefully considered the adverse events related to docetaxel, and the differential adverse events associated with a 3-weekly docetaxel regimen as opposed to a weekly regimen were discussed. The clinical experts indicated that patients receiving weekly docetaxel are more likely to experience painful and debilitating nail dystrophia, whereas this is less common in those receiving the drug 3-weekly. However the 3-weekly regimen was associated with a higher incidence of neutropenia. Additionally the Committee heard from both the clinical experts and the patient representatives that many patients feel that the benefits of treatment with docetaxel outweigh the side effects. The Committee concluded that the adverse events related to docetaxel, when weighed against the potential for beneficial effects, should not preclude recommendation of the use of docetaxel in patients with hormone-refractory metastatic prostate cancer. The Committee considered the economic models put forward by the manufacturer and the Assessment Group. The structure of the Assessment Group model was discussed and it was accepted as suitable and adequate for this appraisal. The Committee discussed the base-case assumptions in the Assessment Group model for patients' extrapolated mean survival, drug and administration costs per cycle, follow-up costs, terminal care costs and the number of cycles received per patient. The Committee accepted these as reasonable assumptions and noted that they were similar to those used in the manufacturer's economic model. The Committee discussed the way in which life years survived were adjusted for health-related quality of life in the Assessment Group model, noting that this had not been done in the manufacturer's model. The Committee noted that no information on utilities had been collected in TAX327 and that, in order to adjust life years survived for health-related quality of life, the Assessment Group had used an assumption based on a study found through a systematic literature review. The Committee further noted that the same utility assumption had been used for all treatment strategies and concurred that it was likely to be a reasonable estimate because it had been derived from a study in a large sample using appropriate methodology. Furthermore, the Committee noted that an ICER of £28,000 had resulted from a one-way sensitivity analysis using a utility assumption derived from the elicitation of preferences of the NHS Value in Health Panel. The Committee considered the potential for quality of life benefits associated with docetaxel treatment over and above mitoxantrone treatment. The Committee discussed the results observed for quality of life response in TAX327 based on the FACT-P questionnaire, and noted that this was the only evidence available and it had not been possible to relate those results to utility values. The Committee agreed with the Assessment Group's conclusion that indirect comparisons of quality of life and pain responses could not have been undertaken because of differences in the definitions and measurements. The Committee concluded that although there is potentially a quality of life benefit of docetaxel over mitoxantrone treatment, it was appropriate not to include it in the base-case assumptions of the economic model because the evidence was insufficient to support doing so. However, the Committee recognised that this approach was conservative and was satisfied by the additional analyses that indicated the inclusion of any quality of life benefit results in an ICER lower than £32,700. Furthermore, the Committee noted that the base-case ICER in the Assessment Group model was robust to a sensitivity analysis in which the reductions in quality of life of the different adverse effects associated with docetaxel and mitoxantrone were modelled. In summary of the Committee's considerations of the cost-effectiveness evidence, it considered the methodology used in Assessment Group's model to be sound, and the base-case assumptions to be either reasonable or conservative. It noted that the base-case ICER of £32,700 had been robust to the one-way sensitivity analyses presented. The Committee therefore concluded that docetaxel within its licensed indications was acceptably cost-effective based on the evidence available at the time of this appraisal. The Committee discussed the uncertainty surrounding the generalisability of the evidence from the RCT to everyday clinical practice. It was aware that the patients enrolled into the pivotal trial (TAX327) generally were younger and had a higher performance status than those who typically present for treatment in the UK. The Committee heard from the clinical experts that performance status, as defined by the Karnofsky score, was an important predictor of the likelihood of benefit from treatment for individual patients, irrespective of age. The Committee therefore decided that the recommendation on the use of docetaxel for patients with hormone-refractory metastatic prostate cancer should be limited to patients who have a Karnofsky score of 60% or more, an entry requirement of the TAX327 RCT. The experts agreed that such an approach would be appropriate. Additionally the Committee considered the potential for the Karnofsky performance-status score to be interpreted in such a way as to potentially discriminate against men who were disabled in a manner unrelated to their likelihood of benefit or harm from docetaxel treatment for prostate cancer. The Committee concluded that for disabled men the restriction in the guidance to a minimum Karnofsky performance-status score should be interpreted on an individual basis at the discretion of the clinician. The Committee also discussed the lack of evidence and the uncertainty surrounding the generalisability of the results of the TAX327 RCT with regard to duration of treatment. The Committee heard testimony from the experts that in clinical practice the duration of treatment is determined by the balance of clinical benefit against the occurrence of adverse events, and in practice it is rare for patients to receive more than six cycles of 3-weekly docetaxel therapy. The Committee therefore concluded, in agreement with the experts and in accordance with the stopping rules of the TAX327 RCT, that treatment should be stopped either in the presence of progression of disease (as evidenced by clinical or laboratory criteria, or by imaging studies) or the presence of severe adverse events, and that patients should not receive more than a maximum of 10 cycles of treatment. Further, the Committee discussed repeat cycles in the event of disease recurrence after completion of the planned course of docetaxel treatment. It considered that there was no evidence to support a recommendation for further cycles of docetaxel therapy if the disease recurs (as evidenced by clinical or laboratory criteria, or by imaging studies) after completion of the planned course of chemotherapy. The Committee heard testimony from clinical experts that the diagnosis of hormone-refractory metastatic prostate cancer may vary in clinical practice in terms of the number and type of hormonal treatments the patient has previously received. The Committee was therefore satisfied that it was not appropriate to limit the recommendation to patients who had received a particular number of hormonal manipulations. In summary, the Committee considered that the use of docetaxel in hormone-refractory metastatic prostate cancer was both clinically and cost effective on the basis of the above considerations and where the treatment protocol was that which was shown to be clinically effective in the pivotal RCT (TAX327), namely the 3-weekly docetaxel regimen administered for a maximum of 10 cycles only.# Recommendations for further research The Committee noted that there are ongoing trials, which include the MRC STAMPEDE study, and trials in which docetaxel plus prednisone or prednisolone is the standard treatment arm and is used in combination with other therapies such as zoledronic acid, strontium-89 and bevacizumab, in the experimental treatment arm. The Committee identified a need for research to assess the quality of life associated with different treatments for hormone-refractory metastatic prostate cancer using generic quality of life instruments that are suitable for the purposes of cost-effectiveness analyses. The Committee also identified a need for research on the effects of docetaxel over a longer follow-up period, and in a patient group that is more representative of a wider patient population in terms of age, performance status and comorbidity, than in the RCTs considered in this appraisal.# Implications for the NHS The Healthcare Commission assesses the performance of NHS organisations in meeting core and developmental standards set by the Department of Health in 'Standards for better health' issued in July 2004. The Secretary of State has directed that the NHS provides funding and resources for medicines and treatments that have been recommended by NICE technology appraisals normally within 3 months from the date that NICE publishes the guidance. Core standard C5 states that healthcare organisations should ensure they conform to NICE technology appraisals. 'Healthcare Standards for Wales' was issued by the Welsh Assembly Government in May 2005 and provides a framework both for self-assessment by healthcare organisations and for external review and investigation by Healthcare Inspectorate Wales. Standard 12a requires healthcare organisations to ensure that patients and service users are provided with effective treatment and care that conforms to NICE technology appraisal guidance. The Assembly Minister for Health and Social Services issued a Direction in October 2003 which requires Local Health Boards and NHS Trusts to make funding available to enable the implementation of NICE technology appraisal guidance, normally within 3 months. When NICE recommends a treatment 'as an option', the NHS must make sure it is available within the period set out in the paragraph above. This means that, if a patient has hormone-refractory metastatic prostate cancer and the doctor responsible for their care thinks that docetaxel is the right treatment, it should be available for use, in line with NICE's recommendations. NICE has developed tools to help organisations implement this guidance (listed below). Costing report and costing template to estimate the savings and costs associated with implementation.# Related guidance NICE has issued the following related guidance. Improving outcomes in urological cancers. NICE cancer service guidance (2002). Prostate cancer: diagnosis and treatment of prostate cancer. NICE clinical guideline 58 (2008). NICE is in the process of developing the following guidance (details available from the NICE website). Atrasentan for hormone-refractory prostate cancer. NICE technology appraisal guidance (suspended).# Review of guidance The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators. The guidance on this technology will be considered for review in June 2009. Andrew DillonChief ExecutiveJune 2006# Appendix C Detail on criteria for audit of the use of docetaxel for the treatment of hormone-refractory metastatic prostate cancer # Possible objectives for an audit An audit could be carried out to ensure the appropriateness of use of docetaxel in men with hormone-refractory metastatic prostate cancer. # Possible patients to be included in the audit An audit could be carried out on men with hormone-refractory metastatic prostate cancer who are seen in a reasonable time period for audit, for example, 6 months to 1 year. It may be useful to include men who were diagnosed and treated sufficiently long ago that the disease may have recurred after completion of the planned course of chemotherapy. # Measures that could be used as a basis for an audit The measures that could be used in an audit of docetaxel for the treatment of hormone-refractory metastatic prostate cancer are as follows. Criterion Standard Exception Definition of terms . A man with hormone-refractory metastatic prostate cancer is offered docetaxel, within its licensed indications, as a treatment option only if his Karnofsky score is 60% or more % of men with hormone-refractory metastatic prostate cancer A. The man has a contraindication to docetaxel Hormone-refractory metastatic prostate cancer is defined either on the basis of biochemical testing (prostate-specific antigen, PSA), findings of imaging studies, or using clinical criteria of progressive metastatic disease despite castrate serum levels of testosterone. Clinicians will need to agree locally on how hormone-refractory metastatic prostate cancer is diagnosed and how the offer of docetaxel as a treatment option are documented, for audit purposes. Karnofsky score of 60% or more means that at least the man is able to care for himself but requires occasional assistance. If the man is disabled in a manner unrelated to his likelihood of benefit or harm from docetaxel treatment of prostate cancer, the Karnofsky score should be interpreted on an individual basis at the discretion of the clinician. See appendix D for more information on the Karnofsky performance score. For details of contraindications, see the summary of product characteristics. . For a man with hormone-refractory metastatic prostate cancer who has been treated with docetaxel, treatment with docetaxel is stopped when any of the following occur: a. the planned treatment of up to 10 cycles is completed or b. the man experiences a severe adverse event or c. there is evidence of progression of disease % of men being treated with docetaxel for metastatic prostate cancer and for whom a or b or c occur None Adverse events are measured using the Common Toxicity Criteria of the US National Cancer Institute, version 2. Evidence of progression of disease is by imaging studies or by clinical or laboratory criteria, which clinicians will need to agree locally, for audit purposes. . Repeat cycles of treatment with docetaxel are offered to a man with hormone-refractory metastatic prostate cancer if the disease recurs after completion of the planned course of chemotherapy % of men with hormone-refractory metastatic prostate cancer in whom the disease recurs after completion of the planned course of chemotherapy None Clinicians will need to agree locally how men in whom the disease recurs after completion of the planned course of chemotherapy are identified, for audit purposes. # Calculation of compliance Compliance (%) with each measure described in the table above is calculated as follows. Number of patients whose care is consistent with the criterion plus number of patients who meet any exception listed x 100 Number of patients to whom the measure applies Clinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.# Appendix D Karnofsky Performance-Status Scores The patient has no complaints and is without evidence of disease. The patient has minor signs/symptoms, but is able to carry out his or her normal activities. The patient demonstrates some signs/symptoms and requires some effort to carry out normal activities. The patient is able to care for self, but is unable to do his or her normal activities or active work. The patient is able to care for self, but requires occasional assistance. The patient requires medical care and much assistance with self care. The patient is disabled and requires special care and assistance. The patient is severely disabled and hospitalisation is indicated; death is not imminent. The patient is very ill with hospitalisation and active life-support treatment necessary. The patient is moribund with fatal process proceeding rapidly. Dead.# Changes after publication March 2014: implementation section updated to clarify that docetaxel is recommended as an option for treating hormone-refractory metastatic prostate cancer. Additional minor maintenance update also carried out. March 2012: minor maintenance# About this guidance NICE technology appraisal guidance is about the use of new and existing medicines The recommendations from this guideline have been incorporated into a NICE Pathway. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.	{'Guidance': 'Docetaxel is recommended, within its licensed indications, as a treatment option for men with hormone-refractory metastatic prostate cancer only if their Karnofsky performance-status score is 60% or more.\n\nIt is recommended that treatment with docetaxel should be stopped:\n\nat the completion of planned treatment of up to 10 cycles, or\n\nif severe adverse events occur, or\n\nin the presence of progression of disease as evidenced by clinical or laboratory criteria, or by imaging studies.\n\nRepeat cycles of treatment with docetaxel are not recommended if the disease recurs after completion of the planned course of chemotherapy.', 'Clinical need and practice': "The prostate gland is present only in men. It is located just below the bladder exit, surrounding the urethra, and is subdivided into three zones: central, transition and peripheral. The peripheral zone, at the back of the prostate, is the part most susceptible to prostate cancer. The extent of prostate cancer is classified into stages I–IV. At stages I and II the disease is confined to the prostate. At stage III the tumour is more locally advanced and at stage IV either it is locally advanced and invading local adjacent structures, or it has associated distant metastases.\n\nThe growth of most prostate cancers is stimulated by testosterone, and hormonal therapies that modify levels of, or responses to, testosterone are standard treatment for men with metastatic disease. Hormonal therapies are initially effective in 80% of men with metastatic prostate cancer, but after around 18 months the disease usually becomes unresponsive to hormone treatment and will progress.\n\nHormone-refractory metastatic prostate cancer is defined on the basis of biochemical testing (prostate-specific antigen, PSA), findings of imaging studies, or using clinical criteria of progressive metastatic disease despite castrate serum levels of testosterone.\n\nData on the epidemiology of hormone-refractory metastatic prostate cancer are limited; therefore inferences must be drawn from available data for prostate cancer. In the UK, prostate cancer is the most common male cancer, excluding non-melanoma skin cancer. In 2001 there were 26,067 new cases in England and 1746 in Wales, giving age-standardised incidence rates of 89.8 and 92.6 per 100,000 men respectively. Prostate cancer is the second most common cause of male cancer deaths, accounting for 13% of them. In 2003 there were 8582 deaths in England and 579 in Wales from prostate cancer, giving age-standardised mortality rates of 27.3 and 28.6 per 100,000 men respectively. It has been estimated that most of the deaths are in patients with hormone-refractory metastatic prostate cancer.\n\nProstate cancer is associated with substantial morbidity that can have a significant impact on the patients, and on their families and carers. Prostate cancer was responsible for almost 40,000 hospital episodes in the 2003–04 financial year, although it is unknown how many of these related to patients with hormone-refractory metastatic prostate cancer. The symptoms of hormone-refractory metastatic prostate cancer may be related to compression of the urethra, metastases to bone and other sites, and adverse effects of treatment. Urinary symptoms include difficulty starting the flow of urine, passing urine more often, and discomfort while passing urine. More than 90% of patients with late-stage prostate cancer develop metastases to bone, and this can cause debilitating and sometimes uncontrollable pain, pathological fractures and spinal cord compression. Patients may receive surgery, radiotherapy, steroids and analgesics as well as hormonal treatment and chemotherapy, and they may suffer adverse effects related to all of these.\n\nThe primary risk factor for prostate cancer is increasing age: 90% of cases are in men older than 60, and 42% in men older than 75. Worldwide, the highest rates are observed in African-American men, with much lower rates seen in men of Asian origin. The cause of prostate cancer is probably multifactorial, involving environmental and genetic factors. Prostate cancer does not occur in castrated men, so testosterone is implicated. High levels of insulin-like growth factor (IGF-1), a protein involved in cell metabolism, may also be involved. About 9% of cases are thought to have a genetic component. Diets high in animal fats and dairy products appear to be associated with increased risk of prostate cancer.\n\nThe prognosis is poor for patients with hormone-refractory metastatic prostate cancer: survival is not expected to exceed between 9 and 12 months. Hormone-refractory metastatic prostate cancer cannot be cured. The aim of treatment is to improve symptoms, prolong life and slow progression of the disease.\n\nThere is no gold standard treatment for hormone-refractory metastatic prostate cancer in the UK. Clinical management is acknowledged to be multimodal rather than sequential and patients may receive a combination of palliative treatments.\n\nTreatment options include second-line hormonal therapy, chemotherapy with or without corticosteroids, and best supportive care. The choice of therapy depends on the symptoms, the site of relapse, the performance status (see appendix D) of the patient and the presence of other comorbidities. Best supportive care can be provided with radiotherapy, bisphosphonates, steroids and analgesics, and is the only option for patients who are too ill to tolerate further active intervention. Tolerability of chemotherapy is of concern, particularly because most patients with prostate cancer are elderly and many have other medical problems.\n\nChemotherapy regimens that have been used to treat the cancer include those based on mitoxantrone, estramustine and taxanes such as docetaxel. Mitoxantrone is widely used in the UK for hormone-refractory metastatic prostate cancer patients who are fit for chemotherapy, even though it is not licensed for this indication. The Institute has been informed by several consultees that a combination of mitoxantrone and prednisolone has come to be accepted as the standard care for this group of patients.\n\nNICE's cancer service guidance 'Improving outcomes in urological cancers' states that chemotherapy should be considered for men with symptomatic hormone-refractory prostate cancer, trials of chemotherapy should be supported, and that palliative radiotherapy should also be available. There are a number of guidelines produced by professional organisations.", 'The technology': "Docetaxel (Sanofi-Aventis) is an anti-neoplastic drug that belongs to a class of drugs known as taxanes. It works by disrupting the microtubular network that is essential for mitotic and interphase cellular functions, causing inhibition of cell division and cell death.\n\nDocetaxel is licensed for use in combination with prednisone or prednisolone for the treatment of patients with hormone-refractory metastatic prostate cancer.\n\nDocetaxel is administered as a 1-hour infusion once every 3\xa0weeks. The recommended dose is 75\xa0mg/m2, with twice daily oral administration of prednisone or prednisolone at a dose of 5\xa0mg.\n\nReported adverse effects of docetaxel include hypersensitivity reactions (presenting as flushing, skin reactions, hypotension and bronchospasm), bone marrow suppression (neutropenia, thrombocytopenia, anaemia), cutaneous reactions, fluid retention, peripheral neuropathy, alopecia, cardiac disorders and tiredness. Contraindications include severe allergic reaction, low white blood cell count due to bone-marrow damage (myelosuppression), or severe liver disease. Premedication with a corticosteroid is usually recommended to help prevent allergic reaction. For full details of side effects and contraindications, see the summary of product characteristics.\n\nThe net price of docetaxel (40\xa0mg/ml) is £162.75 for a 0.5\xa0ml vial and £534.75 for a 2\xa0ml vial (excluding VAT; 'British national formulary', 50th edition). The cost per patient, assuming an average of seven cycles of treatment, would be approximately £8000. Costs may vary in different settings because of negotiated procurement discounts.", 'Evidence and interpretation': "The Appraisal Committee (appendix A) considered evidence from a number of sources (appendix B).\n\n# Clinical effectiveness\n\nOne randomised controlled trial (RCT) that investigated docetaxel within its licensed indications was identified (TAX327). In TAX327, docetaxel plus prednisone or prednisolone was compared with mitoxantrone plus prednisone or prednisolone.\n\nTAX327 was an international, multicentre, open-label, phase III RCT. The trial enrolled 1006 men with metastatic prostate cancer with disease progression during hormonal therapy. The men were randomised to three chemotherapy arms, all of which received prednisone or prednisolone 5\xa0mg orally twice daily. The chemotherapy regimens were: docetaxel at 75\xa0mg/m2 administered every 3\xa0weeks (335 patients); docetaxel at 30\xa0mg/m2 administered weekly for the first 5\xa0weeks in a 6-week cycle (334 patients); and mitoxantrone 12\xa0mg/m2 administered every 3\xa0weeks (337 patients). Up to 10 cycles of treatment were planned for the 3-weekly docetaxel group and the mitoxantrone group, and up to five cycles (of 6\xa0weeks each) in the weekly docetaxel group. Patients in the docetaxel groups also received premedication with dexamethasone.\n\nPatients were required to have a Karnofsky performance-status score (see appendix D) of at least 60%, and stable levels of pain for at least 7\xa0days before randomisation. The median length of follow-up was 20.8\xa0months for the 3-weekly docetaxel group and 20.7\xa0months for the other two groups. The planned treatment was delivered to 98% of patients in the 3-weekly docetaxel group, 96% of patients in the weekly docetaxel group and 99% in the mitoxantrone group. There was a high level of crossover between groups; 27% of patients randomised to the 3‑weekly docetaxel group received mitoxantrone and 20% of patients randomised to the mitoxantrone group received docetaxel.\n\nOverall survival was the primary end point for the trial and was defined as the time from the date of randomisation to the date of death from any cause, or censored at the date of last contact. There was a statistically significant benefit in terms of overall survival for the 3-weekly docetaxel group compared with the mitoxantrone group, with a hazard ratio for death of 0.76 (95% confidence interval [CI] 0.62 to 0.94, p = 0.009). At the time of analysis 166/335 (50%) patients receiving 3-weekly docetaxel and 201/337 (60%) of patients receiving mitoxantrone had died. The median survival was 18.9\xa0months (95% CI 17.0 to 21.2) in the 3-weekly docetaxel group compared with 16.5\xa0months (95% CI 14.4 to 18.6) in the mitoxantrone group. There was no statistically significant difference in overall survival between the weekly docetaxel group and the mitoxantrone group, with a hazard ratio for death of 0.91 (95% CI 0.75 to 1.11).\n\nQuality of life response was defined as a 16-point improvement in score on the Functional Assessment of Cancer Therapy – Prostate (FACT-P) questionnaire, compared with baseline, on two measures at least 3 weeks apart. There was a statistically significant benefit in terms of quality of life response observed for both the 3-weekly docetaxel group (22% [61/278] response; 95% CI 17 to 27%) and the weekly docetaxel group (23% [62/270] response; 95% CI 18 to 28%) compared with the mitoxantrone group (13% [35/267] response; 95% CI 9 to 18%), giving a relative risk of 1.67 (95% CI 1.14 to 2.45, p\xa0=\xa00.009) for the 3-weekly docetaxel group, and 1.75 (95% CI 1.20 to 2.56, p= 0.005) for the weekly docetaxel group. The responses to the FACT-P questionnaire were not mapped to utility values.\n\nIn TAX327 there was a statistically significant benefit in terms of pain response observed for the 3-weekly docetaxel group (35% [54/153] response; 95% CI 27 to 43%) compared with the mitoxantrone group (22% [35/157] response, 95% CI 16 to 29%), giving a relative risk of 1.58 (95% CI 1.1 to 2.27).\n\nIn TAX327 a statistically significant benefit in terms of PSA response was observed for the 3-weekly docetaxel group (45% [131/291] response; 95% CI 40 to 51%) compared with the mitoxantrone group (32% [96/300] response; 95% CI 26 to 37%), giving a relative risk of 1.41 (95% CI 1.14 to 1.73).\n\nIn TAX327 a higher proportion of grade 3 or 4 adverse events was reported in the 3-weekly docetaxel group (45.8%) than in the mitoxantrone group (34.6%). Adverse events were measured using the Common Toxicity Criteria of the US National Cancer Institute, version 2, and were reported for all 997\xa0patients who received their planned treatment.\n\nTo allow for a comparison between docetaxel and relevant comparators other than mitoxantrone plus corticosteroid (for example, other chemotherapy regimens and best supportive care), the Assessment Group searched for RCTs in which other treatments were compared with mitoxantrone plus a corticosteroid, which could then be used as the common comparator. The Assessment Group performed a meta-analysis of the results from three RCTs comparing mitoxantrone plus a corticosteroid with corticosteroid alone. Although various health outcomes other than mortality were measured in those studies (including health-related quality of life and pain response in two of them), the only outcome suitable for the pooling of results was overall survival. The pooled estimate of the hazard ratio for death for mitoxantrone plus corticosteroid versus corticosteroid was 0.99 (95% CI 0.82 to 1.20). This was then compared indirectly, using appropriate statistical analysis, with that from the TAX327 study, giving an indirect hazard ratio for death for docetaxel plus a corticosteroid (prednisone or prednisolone) versus corticosteroid alone (prednisone, prednisolone or hydrocortisone), of 0.752 (95% CI 0.567 to 0.999). The Assessment Report notes that results of the adjusted indirect comparison should be interpreted with caution because the underlying trials differed in patient population and methodology.\n\nTwo other RCTs that investigated the effects of docetaxel in combination with estramustine in patients with hormone-refractory metastatic prostate cancer were submitted in support of the efficacy of docetaxel and included in the Assessment Report. SWOG 9916 compared docetaxel plus estramustine versus mitoxantrone plus prednisone. A statistically significant benefit, in terms of overall survival, was observed for the docetaxel plus estramustine group compared with the mitoxantrone plus prednisone group, with a hazard ratio for death of 0.80 (95% CI 0.67 to 0.97). Oudard and coworkers investigated two different regimens of docetaxel plus prednisone plus estramustine versus mitoxantrone plus prednisone. There was a non-statistically significant reduction in the relative risk of death for patients in the docetaxel groups. The median survival was longer in the docetaxel groups than in the mitoxantrone group, but the difference was not statistically significant.\n\n# Cost effectiveness\n\nThe manufacturer (Sanofi-Aventis) and the Assessment Group provided estimates of cost effectiveness. Some consultees commented on economic issues. The Assessment Group developed its own economic model and critiqued the model submitted by Sanofi-Aventis.\n\nThe Assessment Group's literature search did not yield any suitable cost-effectiveness studies of docetaxel-based treatment regimens. One study was found that compared mitoxantrone and prednisone with prednisone alone and was based on the CCI-NOV-22 RCT. That study was used to inform the follow-up costs of the Assessment Group's economic model.\n\n## Summary of evidence of cost effectiveness from the manufacturer\n\nThe Sanofi-Aventis model estimates the incremental cost per life-year gained (LYG) from docetaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone. No adjustment is made for quality of life. The evaluation is based on an analysis of patient-level data derived from prospective collection of resource use and patient outcome data from the TAX327 trial. Only the 3-weekly regimen of docetaxel is considered in the analysis, in keeping with the licensed recommended dose. Two analyses are presented: the preliminary analysis uses the difference in median survival within the TAX327 trial as the measure of clinical benefit, and the base case uses an estimate of the mean difference in survival extrapolated beyond the trial period; data extrapolation is used to characterise the survival of patients beyond the period of follow-up in the trial. The sponsor submission states that in economic valuation, mean survival times are preferred to medians to provide the best estimate of relative cost effectiveness between two competing interventions. Uncertainty is considered using two different one-way sensitivity analyses, one related to the estimate of survival, and the other to that of costs per patient.\n\nThe base-case result of the Sanofi-Aventis model was £19,483 as the incremental cost per life year gained from docetaxel plus prednisone or prednisolone over mitoxantrone plus prednisone or prednisolone. In the preliminary analysis, the incremental cost per life year gained was £30,280.\n\n## Summary of economic evaluation undertaken by the Assessment Group\n\nThe Assessment Group model estimates the incremental cost per quality-adjusted life year (QALY) gained by using docetaxel plus prednisone or prednisolone compared with the least expensive of a number of treatment comparators not excluded by dominance or extended dominance. It is a probabilistic model that was run for a time horizon of 15\xa0years. A Markov model was used to estimate mean survival and incorporate discounting. Resource utilisation and cost data were estimated from the perspective of the NHS, based on the drug acquisition and administration costs for each intervention and subsequent follow-up costs including the management of side effects, further chemotherapies and palliative care. The Assessment Group undertook a systematic review of literature on measurement of the utility associated with the health-related quality of life of patients with hormone-refractory metastatic prostate cancer, and used this review to inform inputs to the model.\n\nTwo analyses were reported. Analysis 1 compares 3-weekly docetaxel plus prednisone or prednisolone, mitoxantrone plus prednisone or prednisolone, and best supportive care in the form of prednisone or prednisolone alone. Analysis 2 extends this comparison to include the full range of potential comparators identified in the clinical effectiveness review. In both base cases, and all reported sensitivity analyses, the relevant resulting incremental cost-effectiveness ratio (ICER) is that of 3-weekly docetaxel plus prednisone or prednisolone (the licensed regimen) compared with mitoxantrone plus prednisone or prednisolone (the cheapest non-dominated strategy). Uncertainty is characterised using probabilistic sensitivity analysis, as well as three different one-way sensitivity analyses.\n\nIn the base-case results of the Assessment Group model the ICER of 3-weekly docetaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone is estimated to be £32,700 per QALY, with all other strategies compared in both analyses dominated by mitoxantrone plus prednisone or prednisolone. Three one-way sensitivity analyses were undertaken to test the robustness of the model to alternative assumptions about discount rates, utility associated with health-related quality of life and the impact of adverse effects on quality of life. The ICER associated with 3-weekly docetaxel plus prednisone or prednisolone remained fairly robust to these variations, with estimates ranging from £28,000 to £33,000 per QALY.\n\n# Consideration of the evidence\n\nThe Committee reviewed the data available on the clinical and cost effectiveness of docetaxel for hormone-refractory metastatic prostate cancer, having considered evidence on the nature of the condition and the value placed on the benefits of docetaxel by people with hormone-refractory metastatic prostate cancer, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources.\n\nThe Committee noted that prednisone was used as an alternative to prednisolone in the RCTs. It was aware that prednisone is a pro-drug of prednisolone, and that in the UK prednisolone has historically been preferred to prednisone on the grounds that it does not require conversion to the active substance. The Committee concluded that in practice the difference between prednisone and prednisolone was not clinically significant, and it therefore accepted the relevance of the results of international studies to the appraisal.\n\nThe Committee understood from the testimony of the clinical experts that docetaxel is the first treatment to show survival benefit in men with hormone-refractory metastatic prostate cancer. The Committee was persuaded that there was a significant survival advantage for the 3-weekly docetaxel regimen over treatment with mitoxantrone, as opposed to the weekly regimen, for which there was no statistically significant difference. It also considered that this differential effect between the two docetaxel regimens was biologically plausible. The Committee considered evidence from the SWOG 9916 trial and noted that although the regimen was not licensed, its results added weight to the evidence of the effect on overall survival of a 3-weekly regimen of docetaxel compared with treatment with mitoxantrone.\n\nThe Committee carefully considered the adverse events related to docetaxel, and the differential adverse events associated with a 3-weekly docetaxel regimen as opposed to a weekly regimen were discussed. The clinical experts indicated that patients receiving weekly docetaxel are more likely to experience painful and debilitating nail dystrophia, whereas this is less common in those receiving the drug 3-weekly. However the 3-weekly regimen was associated with a higher incidence of neutropenia. Additionally the Committee heard from both the clinical experts and the patient representatives that many patients feel that the benefits of treatment with docetaxel outweigh the side effects. The Committee concluded that the adverse events related to docetaxel, when weighed against the potential for beneficial effects, should not preclude recommendation of the use of docetaxel in patients with hormone-refractory metastatic prostate cancer.\n\nThe Committee considered the economic models put forward by the manufacturer and the Assessment Group. The structure of the Assessment Group model was discussed and it was accepted as suitable and adequate for this appraisal. The Committee discussed the base-case assumptions in the Assessment Group model for patients' extrapolated mean survival, drug and administration costs per cycle, follow-up costs, terminal care costs and the number of cycles received per patient. The Committee accepted these as reasonable assumptions and noted that they were similar to those used in the manufacturer's economic model.\n\nThe Committee discussed the way in which life years survived were adjusted for health-related quality of life in the Assessment Group model, noting that this had not been done in the manufacturer's model. The Committee noted that no information on utilities had been collected in TAX327 and that, in order to adjust life years survived for health-related quality of life, the Assessment Group had used an assumption based on a study found through a systematic literature review. The Committee further noted that the same utility assumption had been used for all treatment strategies and concurred that it was likely to be a reasonable estimate because it had been derived from a study in a large sample using appropriate methodology. Furthermore, the Committee noted that an ICER of £28,000 had resulted from a one-way sensitivity analysis using a utility assumption derived from the elicitation of preferences of the NHS Value in Health Panel.\n\nThe Committee considered the potential for quality of life benefits associated with docetaxel treatment over and above mitoxantrone treatment. The Committee discussed the results observed for quality of life response in TAX327 based on the FACT-P questionnaire, and noted that this was the only evidence available and it had not been possible to relate those results to utility values. The Committee agreed with the Assessment Group's conclusion that indirect comparisons of quality of life and pain responses could not have been undertaken because of differences in the definitions and measurements. The Committee concluded that although there is potentially a quality of life benefit of docetaxel over mitoxantrone treatment, it was appropriate not to include it in the base-case assumptions of the economic model because the evidence was insufficient to support doing so. However, the Committee recognised that this approach was conservative and was satisfied by the additional analyses that indicated the inclusion of any quality of life benefit results in an ICER lower than £32,700. Furthermore, the Committee noted that the base-case ICER in the Assessment Group model was robust to a sensitivity analysis in which the reductions in quality of life of the different adverse effects associated with docetaxel and mitoxantrone were modelled.\n\nIn summary of the Committee's considerations of the cost-effectiveness evidence, it considered the methodology used in Assessment Group's model to be sound, and the base-case assumptions to be either reasonable or conservative. It noted that the base-case ICER of £32,700 had been robust to the one-way sensitivity analyses presented. The Committee therefore concluded that docetaxel within its licensed indications was acceptably cost-effective based on the evidence available at the time of this appraisal.\n\nThe Committee discussed the uncertainty surrounding the generalisability of the evidence from the RCT to everyday clinical practice. It was aware that the patients enrolled into the pivotal trial (TAX327) generally were younger and had a higher performance status than those who typically present for treatment in the UK. The Committee heard from the clinical experts that performance status, as defined by the Karnofsky score, was an important predictor of the likelihood of benefit from treatment for individual patients, irrespective of age. The Committee therefore decided that the recommendation on the use of docetaxel for patients with hormone-refractory metastatic prostate cancer should be limited to patients who have a Karnofsky score of 60% or more, an entry requirement of the TAX327 RCT. The experts agreed that such an approach would be appropriate. Additionally the Committee considered the potential for the Karnofsky performance-status score to be interpreted in such a way as to potentially discriminate against men who were disabled in a manner unrelated to their likelihood of benefit or harm from docetaxel treatment for prostate cancer. The Committee concluded that for disabled men the restriction in the guidance to a minimum Karnofsky performance-status score should be interpreted on an individual basis at the discretion of the clinician.\n\nThe Committee also discussed the lack of evidence and the uncertainty surrounding the generalisability of the results of the TAX327 RCT with regard to duration of treatment. The Committee heard testimony from the experts that in clinical practice the duration of treatment is determined by the balance of clinical benefit against the occurrence of adverse events, and in practice it is rare for patients to receive more than six cycles of 3-weekly docetaxel therapy. The Committee therefore concluded, in agreement with the experts and in accordance with the stopping rules of the TAX327 RCT, that treatment should be stopped either in the presence of progression of disease (as evidenced by clinical or laboratory criteria, or by imaging studies) or the presence of severe adverse events, and that patients should not receive more than a maximum of 10 cycles of treatment. Further, the Committee discussed repeat cycles in the event of disease recurrence after completion of the planned course of docetaxel treatment. It considered that there was no evidence to support a recommendation for further cycles of docetaxel therapy if the disease recurs (as evidenced by clinical or laboratory criteria, or by imaging studies) after completion of the planned course of chemotherapy.\n\nThe Committee heard testimony from clinical experts that the diagnosis of hormone-refractory metastatic prostate cancer may vary in clinical practice in terms of the number and type of hormonal treatments the patient has previously received. The Committee was therefore satisfied that it was not appropriate to limit the recommendation to patients who had received a particular number of hormonal manipulations.\n\nIn summary, the Committee considered that the use of docetaxel in hormone-refractory metastatic prostate cancer was both clinically and cost effective on the basis of the above considerations and where the treatment protocol was that which was shown to be clinically effective in the pivotal RCT (TAX327), namely the 3-weekly docetaxel regimen administered for a maximum of 10\xa0cycles only.", 'Recommendations for further research': 'The Committee noted that there are ongoing trials, which include the MRC STAMPEDE study, and trials in which docetaxel plus prednisone or prednisolone is the standard treatment arm and is used in combination with other therapies such as zoledronic acid, strontium-89 and bevacizumab, in the experimental treatment arm.\n\nThe Committee identified a need for research to assess the quality of life associated with different treatments for hormone-refractory metastatic prostate cancer using generic quality of life instruments that are suitable for the purposes of cost-effectiveness analyses. The Committee also identified a need for research on the effects of docetaxel over a longer follow-up period, and in a patient group that is more representative of a wider patient population in terms of age, performance status and comorbidity, than in the RCTs considered in this appraisal.', 'Implications for the NHS ': "The Healthcare Commission assesses the performance of NHS organisations in meeting core and developmental standards set by the Department of Health in 'Standards for better health' issued in July 2004. The Secretary of State has directed that the NHS provides funding and resources for medicines and treatments that have been recommended by NICE technology appraisals normally within 3 months from the date that NICE publishes the guidance. Core standard C5 states that healthcare organisations should ensure they conform to NICE technology appraisals.\n\n'Healthcare Standards for Wales' was issued by the Welsh Assembly Government in May 2005 and provides a framework both for self-assessment by healthcare organisations and for external review and investigation by Healthcare Inspectorate Wales. Standard 12a requires healthcare organisations to ensure that patients and service users are provided with effective treatment and care that conforms to NICE technology appraisal guidance. The Assembly Minister for Health and Social Services issued a Direction in October 2003 which requires Local Health Boards and NHS Trusts to make funding available to enable the implementation of NICE technology appraisal guidance, normally within 3 months.\n\nWhen NICE recommends a treatment 'as an option', the NHS must make sure it is available within the period set out in the paragraph above. This means that, if a patient has hormone-refractory metastatic prostate cancer and the doctor responsible for their care thinks that docetaxel is the right treatment, it should be available for use, in line with NICE's recommendations.\n\nNICE has developed tools to help organisations implement this guidance (listed below).\n\nCosting report and costing template to estimate the savings and costs associated with implementation.", 'Related guidance': 'NICE has issued the following related guidance.\n\nImproving outcomes in urological cancers.\n NICE cancer service guidance (2002).\n\nProstate cancer: diagnosis and treatment of prostate cancer. NICE clinical guideline 58 (2008).\n\nNICE is in the process of developing the following guidance (details available from the NICE website).\n\nAtrasentan for hormone-refractory prostate cancer. NICE technology appraisal guidance (suspended).', 'Review of guidance': 'The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators.\n\nThe guidance on this technology will be considered for review in June 2009.\n\nAndrew DillonChief ExecutiveJune 2006', 'Appendix C Detail on criteria for audit of the use of docetaxel for the treatment of hormone-refractory metastatic prostate cancer': '# Possible objectives for an audit\n\nAn audit could be carried out to ensure the appropriateness of use of docetaxel in men with hormone-refractory metastatic prostate cancer.\n\n# Possible patients to be included in the audit\n\nAn audit could be carried out on men with hormone-refractory metastatic prostate cancer who are seen in a reasonable time period for audit, for example, 6 months to 1 year. It may be useful to include men who were diagnosed and treated sufficiently long ago that the disease may have recurred after completion of the planned course of chemotherapy.\n\n# Measures that could be used as a basis for an audit\n\nThe measures that could be used in an audit of docetaxel for the treatment of hormone-refractory metastatic prostate cancer are as follows.\n\nCriterion\n\nStandard\n\nException\n\nDefinition of terms\n\n. A man with hormone-refractory metastatic prostate cancer is offered docetaxel, within its licensed indications, as a treatment option only if his Karnofsky score is 60% or more\n\n% of men with hormone-refractory metastatic prostate cancer\n\nA. The man has a contraindication to docetaxel\n\nHormone-refractory metastatic prostate cancer is defined either on the basis of biochemical testing (prostate-specific antigen, PSA), findings of imaging studies, or using clinical criteria of progressive metastatic disease despite castrate serum levels of testosterone. Clinicians will need to agree locally on how hormone-refractory metastatic prostate cancer is diagnosed and how the offer of docetaxel as a treatment option are documented, for audit purposes.\n\nKarnofsky score of 60% or more means that at least the man is able to care for himself but requires occasional assistance. If the man is disabled in a manner unrelated to his likelihood of benefit or harm from docetaxel treatment of prostate cancer, the Karnofsky score should be interpreted on an individual basis at the discretion of the clinician. See appendix D for more information on the Karnofsky performance score.\n\nFor details of contraindications, see the summary of product characteristics.\n\n. For a man with hormone-refractory metastatic prostate cancer who has been treated with docetaxel, treatment with docetaxel is stopped when any of the following occur:\n\na. the planned treatment of up to 10 cycles is completed or\n\nb. the man experiences a severe adverse event or\n\nc. there is evidence of progression of disease\n\n% of men being treated with docetaxel for metastatic prostate cancer and for whom a or b or c occur\n\nNone\n\nAdverse events are measured using the Common Toxicity Criteria of the US National Cancer Institute, version 2.\n\nEvidence of progression of disease is by imaging studies or by clinical or laboratory criteria, which clinicians will need to agree locally, for audit purposes.\n\n. Repeat cycles of treatment with docetaxel are offered to a man with hormone-refractory metastatic prostate cancer if the disease recurs after completion of the planned course of chemotherapy\n\n% of men with hormone-refractory metastatic prostate cancer in whom the disease recurs after completion of the planned course of chemotherapy\n\nNone\n\nClinicians will need to agree locally how men in whom the disease recurs after completion of the planned course of chemotherapy are identified, for audit purposes.\n\n# Calculation of compliance\n\nCompliance (%) with each measure described in the table above is calculated as follows.\n\nNumber of patients whose care is consistent with the criterion plus number of patients who meet any exception listed\n\n\n\nx 100\n\nNumber of patients to whom the measure applies\n\nClinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.', 'Appendix D Karnofsky Performance-Status Scores ': '%\n\nThe patient has no complaints and is without evidence of disease.\n\n%\n\n\n\nThe patient has minor signs/symptoms, but is able to carry out his or her normal activities.\n\n%\n\n\n\nThe patient demonstrates some signs/symptoms and requires some effort to carry out normal activities.\n\n%\n\n\n\nThe patient is able to care for self, but is unable to do his or her normal activities or active work.\n\n%\n\nThe patient is able to care for self, but requires occasional assistance.\n\n%\n\nThe patient requires medical care and much assistance with self care.\n\n%\n\nThe patient is disabled and requires special care and assistance.\n\n%\n\n\n\nThe patient is severely disabled and hospitalisation is indicated; death is not imminent.\n\n%\n\n\n\nThe patient is very ill with hospitalisation and active life-support treatment necessary.\n\n%\n\nThe patient is moribund with fatal process proceeding rapidly.\n\n%\n\nDead.', 'Changes after publication': 'March 2014: implementation section updated to clarify that docetaxel is recommended as an option for treating hormone-refractory metastatic prostate cancer. Additional minor maintenance update also carried out.\n\nMarch 2012: minor maintenance', 'About this guidance': 'NICE technology appraisal guidance is about the use of new and existing medicines\n\nThe recommendations from this guideline have been incorporated into a NICE Pathway. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.'}	https://www.nice.org.uk/guidance/ta101	Evidence-based recommendations on docetaxel for treating hormone-refractory metastatic prostate cancer in adults.
41af6a08dae724c3bca4e8aae2293755de3306c9	nice	Short-term circulatory support with left ventricular assist devices as a bridge to cardiac transplantation or recovery	Short-term circulatory support with left ventricular assist devices as a bridge to cardiac transplantation or recovery # Guidance Limited evidence on the safety and efficacy of short-term circulatory support with left ventricular assist devices (LVADs) as a bridge to cardiac transplantation or recovery appears adequate to support the use of this procedure provided that the normal arrangements are in place for audit and clinical governance. Clinicians should ensure that patients fully understand the high complication rates associated with this procedure and that the procedure is a temporary measure. In addition, use of NICE's information for the public is recommended. Publication of further research will be useful, particularly on the use of this procedure in patients with cardiogenic shock following acute myocardial infarction.# The procedure # Indications The management of patients with end-stage heart failure or acute heart failure from naturally reversible causes is challenging; it may involve combination medical therapy (including inotropic support), intra-aortic balloon pumping and heart transplantation. Short-term circulatory support with a left ventricular assist device (LVAD) may be indicated for patients with end-stage heart failure (of any aetiology) who are awaiting a donor heart for transplantation, and for patients with a severe acute heart failure syndrome from which myocardial recovery is anticipated (such as acute myocarditis). An LVAD is sometimes used if weaning from cardiopulmonary bypass after cardiac surgery fails. # Outline of the procedure A number of LVADs that increase cardiac output by providing mechanical support to the failing left ventricle are available. The choice of device depends on the patient's body size, the length of time support is required, the degree of support needed and the type of blood flow desired. Implantation of an LVAD is done under general anaesthesia through a chest incision; surgery usually takes several hours. The inflow pipe of the LVAD is inserted into the left side of the heart, usually the left ventricle, and the outflow pipe is inserted into the systemic arterial system, usually the aorta. The LVAD pumps oxygenated blood from the failing left ventricle into the systemic arterial system under pressure. # Efficacy In the active arm of a non-randomised controlled study, 78% (32/41) of patients survived for a mean of 215 days with LVAD support. In another comparative study, 81% (13/16) of patients survived to transplant (duration of support not stated). One case series showed that at 30 days of bridging to transplantation with an LVAD, survival was 83%, falling to 19% after 24 months' support. In a non-randomised controlled trial, post-transplant survival of patients bridged on LVAD support was 66% (21/32) at 41 months, compared with 67% (98/146) of patients at 36 months who had a transplant without circulatory support, although patients in the latter group were significantly older. One case series of 243 patients in whom LVADs were used to bridge to transplantation reported actuarial post-transplant survival of 91% at 1 year, 70% at 5 years and 40% at 10 years. Results from case series included in a systematic review showed that between 60% (12/20) and 83% (5/6) of patients survived to transplantation or were still alive awaiting transplantation on LVAD support. Of the total cases of bridge to recovery reported, 58% (7/12) of patients survived to final follow-up; successful explanation of the device or weaning from support was achieved in all these patients. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers commented that LVADs may improve quality of life and survival rates in patients with an otherwise fatal condition while waiting for transplantation. # Safety Definition of infection varied among the studies identified. In a case series documented in a systematic review, rates of infection during LVAD support ranging from 0% (0/10) to 100% (5/5) were reported. A non-randomised controlled trial noted infection in 8% (1/13) of patients during LVAD bridging, and one case series reported an infection rate of 18% (43/243). Definitions of cerebral events varied between studies, which made interpretation difficult. Cerebral infarction causing stroke was found to have occurred in 21% (55/264) of patients in 1 series. In a second case series, cerebrovascular accident occurred in 5% (13/243) of patients, and stroke occurred in 5% (13/243) of patients during support time (mean 78 days). In a third series, a neurological event (not defined) occurred in 8% (1/13) of patients. In a systematic review, significant haemorrhage was reported in between 10% (1/10) and 30% (6/20) of patients. Re-operation because of bleeding was required in 31% (4/13) of patients in one series. Other complications reported during LVAD support were renal failure, respiratory failure and haemolysis. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers noted that adverse events relating to the procedure include bleeding, infection, device malfunction, haemolysis, peripheral ischaemia and perforation of a ventricle or the aorta. In addition, they noted that theoretical complications include device-related thrombosis and device-related strokes. # Other comments This guidance refers to patients for whom other treatments such as intra-aortic balloon pumping would be ineffective, who are considered eligible for heart transplantation, or who have acute severe heart failure that is likely to be reversible (such as acute myocarditis). It was noted that other patients might potentially benefit from this procedure, such as patients who cannot be weaned off cardiopulmonary bypass after cardiac surgery and patients with cardiogenic shock after acute myocardial infarction. It was noted that a number of different devices are available for this procedure and that the technology is evolving rapidly. Some devices include a right-ventricular assist device (biventricular assist devices). The Institute may review this guidance upon publication of further evidence. It was also noted that implantation of an LVAD could unmask previously subclinical right ventricular dysfunction. These recommendations exclude circulatory support with left ventricular devices as destination therapy.# Further information NICE has published a guideline on chronic heart failure in adults: diagnosis and management. The National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme has produced a report on the Evaluation of the ventricular assist device programme in the UK (EVAD), which was published in November 2006. # Sources of evidence The evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of left ventricular assist devices as a bridge to transplantation or to recovery. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Limited evidence on the safety and efficacy of short-term circulatory support with left ventricular assist devices (LVADs) as a bridge to cardiac transplantation or recovery appears adequate to support the use of this procedure provided that the normal arrangements are in place for audit and clinical governance.\n\nClinicians should ensure that patients fully understand the high complication rates associated with this procedure and that the procedure is a temporary measure. In addition, use of NICE's information for the public is recommended.\n\nPublication of further research will be useful, particularly on the use of this procedure in patients with cardiogenic shock following acute myocardial infarction.", 'The procedure': "# Indications\n\nThe management of patients with end-stage heart failure or acute heart failure from naturally reversible causes is challenging; it may involve combination medical therapy (including inotropic support), intra-aortic balloon pumping and heart transplantation.\n\nShort-term circulatory support with a left ventricular assist device (LVAD) may be indicated for patients with end-stage heart failure (of any aetiology) who are awaiting a donor heart for transplantation, and for patients with a severe acute heart failure syndrome from which myocardial recovery is anticipated (such as acute myocarditis). An LVAD is sometimes used if weaning from cardiopulmonary bypass after cardiac surgery fails.\n\n# Outline of the procedure\n\nA number of LVADs that increase cardiac output by providing mechanical support to the failing left ventricle are available. The choice of device depends on the patient's body size, the length of time support is required, the degree of support needed and the type of blood flow desired.\n\nImplantation of an LVAD is done under general anaesthesia through a chest incision; surgery usually takes several hours. The inflow pipe of the LVAD is inserted into the left side of the heart, usually the left ventricle, and the outflow pipe is inserted into the systemic arterial system, usually the aorta. The LVAD pumps oxygenated blood from the failing left ventricle into the systemic arterial system under pressure.\n\n# Efficacy\n\nIn the active arm of a non-randomised controlled study, 78% (32/41) of patients survived for a mean of 215\xa0days with LVAD support. In another comparative study, 81% (13/16) of patients survived to transplant (duration of support not stated). One case series showed that at 30\xa0days of bridging to transplantation with an LVAD, survival was 83%, falling to 19% after 24\xa0months' support.\n\nIn a non-randomised controlled trial, post-transplant survival of patients bridged on LVAD support was 66% (21/32) at 41\xa0months, compared with 67% (98/146) of patients at 36\xa0months who had a transplant without circulatory support, although patients in the latter group were significantly older. One case series of 243\xa0patients in whom LVADs were used to bridge to transplantation reported actuarial post-transplant survival of 91% at 1\xa0year, 70% at 5\xa0years and 40% at 10\xa0years. Results from case series included in a systematic review showed that between 60% (12/20) and 83% (5/6) of patients survived to transplantation or were still alive awaiting transplantation on LVAD support.\n\nOf the total cases of bridge to recovery reported, 58% (7/12) of patients survived to final follow-up; successful explanation of the device or weaning from support was achieved in all these patients. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers commented that LVADs may improve quality of life and survival rates in patients with an otherwise fatal condition while waiting for transplantation.\n\n# Safety\n\nDefinition of infection varied among the studies identified. In a case series documented in a systematic review, rates of infection during LVAD support ranging from 0% (0/10) to 100% (5/5) were reported. A non-randomised controlled trial noted infection in 8% (1/13) of patients during LVAD bridging, and one case series reported an infection rate of 18% (43/243).\n\nDefinitions of cerebral events varied between studies, which made interpretation difficult. Cerebral infarction causing stroke was found to have occurred in 21% (55/264) of patients in 1\xa0series. In a second case series, cerebrovascular accident occurred in 5% (13/243) of patients, and stroke occurred in 5% (13/243) of patients during support time (mean 78 days). In a third series, a neurological event (not defined) occurred in 8% (1/13) of patients.\n\nIn a systematic review, significant haemorrhage was reported in between 10% (1/10) and 30% (6/20) of patients. Re-operation because of bleeding was required in 31% (4/13) of patients in one series.\n\nOther complications reported during LVAD support were renal failure, respiratory failure and haemolysis. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers noted that adverse events relating to the procedure include bleeding, infection, device malfunction, haemolysis, peripheral ischaemia and perforation of a ventricle or the aorta. In addition, they noted that theoretical complications include device-related thrombosis and device-related strokes.\n\n# Other comments\n\nThis guidance refers to patients for whom other treatments such as intra-aortic balloon pumping would be ineffective, who are considered eligible for heart transplantation, or who have acute severe heart failure that is likely to be reversible (such as acute myocarditis). It was noted that other patients might potentially benefit from this procedure, such as patients who cannot be weaned off cardiopulmonary bypass after cardiac surgery and patients with cardiogenic shock after acute myocardial infarction.\n\nIt was noted that a number of different devices are available for this procedure and that the technology is evolving rapidly. Some devices include a right-ventricular assist device (biventricular assist devices). The Institute may review this guidance upon publication of further evidence.\n\nIt was also noted that implantation of an LVAD could unmask previously subclinical right ventricular dysfunction.\n\nThese recommendations exclude circulatory support with left ventricular devices as destination therapy.", 'Further information': 'NICE has published a guideline on chronic heart failure in adults: diagnosis and management.\n\nThe National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme has produced a report on the Evaluation of the ventricular assist device programme in the UK (EVAD), which was published in November 2006.\n\n# Sources of evidence\n\nThe evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of left ventricular assist devices as a bridge to transplantation or to recovery.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg177
f892fe13609996232057a9e1912d338fc17b462e	nice	Tonsillectomy using ultrasonic scalpel	Tonsillectomy using ultrasonic scalpel # Guidance Current evidence on the safety and efficacy of tonsillectomy using ultrasonic scalpel appears adequate to support the use of this technique provided that normal arrangements are in place for consent, audit and clinical governance. The use of ultrasonic scalpel for tonsillectomy may result in higher rates of secondary haemorrhage than some other techniques, and clinicians wishing to use ultrasound scalpel should be specifically trained. The British Association of Otorhinolaryngologists – Head and Neck Surgeons has agreed to produce standards for training. Surgeons should ensure that patients or their parents/carers understand the risk of haemorrhage after tonsillectomy using ultrasonic scalpel. In addition, use of NICE's information for the public is recommended. Surgeons should audit and review rates of haemorrhage following tonsillectomy in their own practices and in the context of the techniques they use. Publication of further information about the influence of different techniques and other factors (such as age) on the incidence of haemorrhage after tonsillectomy would be useful in guiding future practice.# The procedure # Indications Indications for tonsillectomy include recurrent acute or chronic tonsillitis, peritonsillar abscess and pharyngeal obstruction/obstructive sleep apnoea. Life-threatening complications of these conditions are rare and the main aim of surgery is to relieve symptoms. Tonsillectomy has been typically undertaken by 'cold steel' using traditional surgical instruments. It consists of two stages: removal of the tonsil followed by haemostasis. Bleeding is controlled by pressure, then by ligatures. The use of ligatures may be supplemented by diathermy and the use of packs. Techniques using thermal energy can be used in tonsillectomy for dissection and haemostasis. Diathermy uses radiofrequency energy applied directly to the tissue, and it can be bipolar or monopolar. The heat generated is used in dissection to incise the mucosa and remove the tonsil, and for haemostasis, by coagulating the bleeding vessels. Other methods that use thermal energy include coblation and lasers. # Outline of the procedure Tonsillectomy using ultrasonic scalpel uses ultrasonic energy to simultaneously dissect through tissues and seal blood vessels. A disposable blade is used, which vibrates at ultrasonic frequency, thereby cutting the tissue. This vibration also transfers energy to the tissue, which leads to coagulation and haemostasis. The temperature generated by the vibration is 55–100ºC and is lower than that produced by other thermal methods such as diathermy or lasers. # Efficacy Six studies assessed pain following tonsillectomy using ultrasonic scalpel, cold-steel dissection or diathermy. Pain scores up to 7 days were similar for the three methods. Three randomised studies reported on pain at 2 weeks or more. In one study of 120 patients, only three patients reported any pain on day 14, all from the diathermy group (n = 59). In another study in which 32 patients had ultrasonic-scalpel tonsillectomy on one side and blunt-dissection tonsillectomy on the other, pain was significantly greater on the ultrasonic-scalpel side during the second week. Return to normal diet was assessed in four studies, all of which reported that patients who had undergone tonsillectomy with the ultrasonic scalpel returned to normal diet at a similar time or earlier than those who had undergone cold-steel dissection or diathermy. In one study of 172 patients, return to normal diet was reported by 44% (43/97) of the ultrasonic scalpel group at day 1 and by 74% (72/97) at day 3, compared with 23% (17/75) and 47% (35/75) of the diathermy group, respectively. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers did not have any particular concerns about the efficacy of this procedure but noted that the evidence base was still small and that a number of the studies had methodological limitations. # Safety Bleeding is an important complication of tonsillectomy. It can occur intraoperatively, during the first 24 hours after the operation (defined in most studies as primary haemorrhage) or after 24 hours (secondary haemorrhage). Postoperative haemorrhage may require the patient to be re-admitted to hospital and may sometimes necessitate further surgery. In general, primary haemorrhage rates appeared to be lower with the ultrasonic scalpel than with cold-steel dissection or diathermy. In a retrospective review of 316 patients, primary haemorrhage occurred in 1% (1/70) of patients in the ultrasonic-scalpel group, 3% (3/109) in the diathermy group and 3% (4/132) in the cold-steel-dissection group. In a retrospective review of 407 patients, primary haemorrhage rates were 1% (1/165), 7% (7/102) and 2% (3/140) for patients treated with ultrasonic scalpel, dissection with monopolar diathermy and dissection with bipolar diathermy, respectively. However, in most of the studies other techniques (such as ligatures or diathermy) were needed in addition to the ultrasonic scalpel to achieve haemostasis. Secondary haemorrhage rates varied among the studies. In a randomised controlled trial of 120 children, secondary haemorrhage occurred in 8% (5/61) of children in the ultrasonic group, compared with 5% (3/59) in the diathermy group, although this difference was not statistically significant. In a small randomised controlled trial of 21 patients undergoing ultrasonic-scalpel tonsillectomy on one side and diathermy on the other side, there were two cases of delayed bleeding – one with each method. Another within-patient comparative study of ultrasonic-scalpel and cold-steel tonsillectomy reported that 11% (3/28) of patients had delayed bleeding, all occurring on the ultrasonic-scalpel side. These data are in general agreement with results from the National Prospective Tonsillectomy Audit, which found that the lowest rates of secondary haemorrhage (requiring or not requiring further surgery) were associated with cold-steel dissection with suture haemostasis; higher rates were associated with other techniques such as coblation and with the use of diathermy for both dissection and haemostasis. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers stated that the safety is much the same as for any other method of tonsillectomy; however, it appeared that there is a slight increase in postoperative haemorrhage compared with cold-steel dissection. # Other comments It was noted that the National Prospective Tonsillectomy Audit recommends that all surgeons undertaking tonsillectomy should be trained in the use of cold-steel dissection and ligature haemostasis, as well as in the use of any electrosurgical techniques.# Further information NICE has published guidance on electrosurgery (diathermy and coblation) for tonsillectomy. # Sources of evidence The evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of tonsillectomy using ultrasonic scalpel, August 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of tonsillectomy using ultrasonic scalpel appears adequate to support the use of this technique provided that normal arrangements are in place for consent, audit and clinical governance.\n\nThe use of ultrasonic scalpel for tonsillectomy may result in higher rates of secondary haemorrhage than some other techniques, and clinicians wishing to use ultrasound scalpel should be specifically trained. The British Association of Otorhinolaryngologists – Head and Neck Surgeons has agreed to produce standards for training.\n\nSurgeons should ensure that patients or their parents/carers understand the risk of haemorrhage after tonsillectomy using ultrasonic scalpel. In addition, use of NICE's information for the public is recommended.\n\nSurgeons should audit and review rates of haemorrhage following tonsillectomy in their own practices and in the context of the techniques they use. Publication of further information about the influence of different techniques and other factors (such as age) on the incidence of haemorrhage after tonsillectomy would be useful in guiding future practice.", 'The procedure': "# Indications\n\nIndications for tonsillectomy include recurrent acute or chronic tonsillitis, peritonsillar abscess and pharyngeal obstruction/obstructive sleep apnoea. Life-threatening complications of these conditions are rare and the main aim of surgery is to relieve symptoms.\n\nTonsillectomy has been typically undertaken by 'cold steel' using traditional surgical instruments. It consists of two stages: removal of the tonsil followed by haemostasis. Bleeding is controlled by pressure, then by ligatures. The use of ligatures may be supplemented by diathermy and the use of packs.\n\nTechniques using thermal energy can be used in tonsillectomy for dissection and haemostasis. Diathermy uses radiofrequency energy applied directly to the tissue, and it can be bipolar or monopolar. The heat generated is used in dissection to incise the mucosa and remove the tonsil, and for haemostasis, by coagulating the bleeding vessels. Other methods that use thermal energy include coblation and lasers.\n\n# Outline of the procedure\n\nTonsillectomy using ultrasonic scalpel uses ultrasonic energy to simultaneously dissect through tissues and seal blood vessels. A disposable blade is used, which vibrates at ultrasonic frequency, thereby cutting the tissue. This vibration also transfers energy to the tissue, which leads to coagulation and haemostasis. The temperature generated by the vibration is 55–100ºC and is lower than that produced by other thermal methods such as diathermy or lasers.\n\n# Efficacy\n\nSix studies assessed pain following tonsillectomy using ultrasonic scalpel, cold-steel dissection or diathermy. Pain scores up to 7 days were similar for the three methods. Three randomised studies reported on pain at 2 weeks or more. In one study of 120 patients, only three patients reported any pain on day 14, all from the diathermy group (n = 59). In another study in which 32 patients had ultrasonic-scalpel tonsillectomy on one side and blunt-dissection tonsillectomy on the other, pain was significantly greater on the ultrasonic-scalpel side during the second week.\n\nReturn to normal diet was assessed in four studies, all of which reported that patients who had undergone tonsillectomy with the ultrasonic scalpel returned to normal diet at a similar time or earlier than those who had undergone cold-steel dissection or diathermy. In one study of 172 patients, return to normal diet was reported by 44% (43/97) of the ultrasonic scalpel group at day 1 and by 74% (72/97) at day 3, compared with 23% (17/75) and 47% (35/75) of the diathermy group, respectively. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers did not have any particular concerns about the efficacy of this procedure but noted that the evidence base was still small and that a number of the studies had methodological limitations.\n\n# Safety\n\nBleeding is an important complication of tonsillectomy. It can occur intraoperatively, during the first 24 hours after the operation (defined in most studies as primary haemorrhage) or after 24 hours (secondary haemorrhage). Postoperative haemorrhage may require the patient to be re-admitted to hospital and may sometimes necessitate further surgery.\n\nIn general, primary haemorrhage rates appeared to be lower with the ultrasonic scalpel than with cold-steel dissection or diathermy. In a retrospective review of 316 patients, primary haemorrhage occurred in 1% (1/70) of patients in the ultrasonic-scalpel group, 3% (3/109) in the diathermy group and 3% (4/132) in the cold-steel-dissection group.\n\nIn a retrospective review of 407 patients, primary haemorrhage rates were 1% (1/165), 7% (7/102) and 2% (3/140) for patients treated with ultrasonic scalpel, dissection with monopolar diathermy and dissection with bipolar diathermy, respectively. However, in most of the studies other techniques (such as ligatures or diathermy) were needed in addition to the ultrasonic scalpel to achieve haemostasis.\n\nSecondary haemorrhage rates varied among the studies. In a randomised controlled trial of 120 children, secondary haemorrhage occurred in 8% (5/61) of children in the ultrasonic group, compared with 5% (3/59) in the diathermy group, although this difference was not statistically significant. In a small randomised controlled trial of 21 patients undergoing ultrasonic-scalpel tonsillectomy on one side and diathermy on the other side, there were two cases of delayed bleeding – one with each method. Another within-patient comparative study of ultrasonic-scalpel and cold-steel tonsillectomy reported that 11% (3/28) of patients had delayed bleeding, all occurring on the ultrasonic-scalpel side. These data are in general agreement with results from the National Prospective Tonsillectomy Audit, which found that the lowest rates of secondary haemorrhage (requiring or not requiring further surgery) were associated with cold-steel dissection with suture haemostasis; higher rates were associated with other techniques such as coblation and with the use of diathermy for both dissection and haemostasis. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers stated that the safety is much the same as for any other method of tonsillectomy; however, it appeared that there is a slight increase in postoperative haemorrhage compared with cold-steel dissection.\n\n# Other comments\n\nIt was noted that the National Prospective Tonsillectomy Audit recommends that all surgeons undertaking tonsillectomy should be trained in the use of cold-steel dissection and ligature haemostasis, as well as in the use of any electrosurgical techniques.", 'Further information': 'NICE has published guidance on electrosurgery (diathermy and coblation) for tonsillectomy.\n\n# Sources of evidence\n\nThe evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of tonsillectomy using ultrasonic scalpel, August 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg178
71c98cbe0a0b557485d13d6015b6985622fdaabe	nice	Percutaneous cementoplasty for palliative treatment of bony malignancies	Percutaneous cementoplasty for palliative treatment of bony malignancies # Guidance Current evidence on the safety and efficacy of percutaneous cementoplasty for the palliative treatment of bony malignancies is limited, but appears adequate to support the use of this procedure in patients for whom other treatments have failed, provided that the normal arrangements are in place for consent, audit and clinical governance. Patient selection should be carried out in the context of a multidisciplinary team, which may include specialists in radiology, oncology, radiotherapy, orthopaedics, pain management and palliative care.# The procedure # Indications Radiotherapy is commonly used to treat patients with painful bony malignancy, although pain may not be relieved for up to 2 weeks after the procedure. Conservative therapy involves analgesia (often with narcotic drugs) and bed rest. However, in some patients, pain remains refractory to both pharmacological and radiation treatment. Percutaneous cementoplasty is indicated for patients with painful bone metastases resulting from tumours elsewhere in the body or, less frequently, with primary bone tumours. The aim of the procedure is to reduce pain and stabilise bones. Cementoplasty is the generic term for this procedure. Its use in vertebrae is commonly termed vertebroplasty (see section 3.1), and when treating the sacrum it may be described as sacroplasty. # Outline of the procedure Percutaneous cementoplasty involves the injection of acrylic bone cement into malignant bone cavities in order to relieve pain or stabilise the bone, or both. Percutaneous cementoplasty may be performed under general anaesthesia or, more commonly, using conscious sedation and local anaesthesia. A small skin incision is made and a 10–12-gauge trocar or needle is passed into the bone under fluoroscopic guidance. Cement containing a radiopaque agent is used for this procedure. Visualisation of the cement during injection via multi-plane fluoroscopy is essential in order to limit extra-osseous leakage of cement. If leakage outside the bone occurs, the injection is halted while the cement hardens and plugs the leak, or for the needle to be repositioned. Once the procedure is complete, the patient should remain recumbent and should not bear weight while the cement hardens. # Efficacy In 14 patients in a case series, pain scores (measured using a self-reported visual analogue scale) improved from a mean 8.8 points at baseline to 1.9 points after cementoplasty (p < 0.0016). In another two studies, good pain relief was achieved in 82% (9/11) and 93% (13/14) of patients. In another case series, 22% (4/18) of patients had 'total improvement' in pain (no pain without analgesics), while 39% (7/18) had clear improvement at 72-hour follow-up. Two studies reported mobility outcomes. One reported overall improvements in mobility in 93% (13/14) of patients at 1-week follow-up; the other study of 18 patients reported an improvement in mean walking score (on a 0–4 scale) from 1.1 at baseline to 2.1 at 1-month follow-up. The evaluation of technical success varied across the studies. In one case series, cementoplasty was considered technically successful in all 14 patients; in another, good filling was demonstrated on postoperative computed tomography scans in 39% (7/18) of patients. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers noted that the procedure was a variation on the existing technique of vertebroplasty. # Safety Among four case series, leakage of injected cement was reported in 6% (1/18), 14% (2/14), 27% (3/11) and 50% (9/18) of patients, although the definition of leakage varied between studies. Symptoms relating to cement leakage were reported in between 6% (1/18) and 11% (2/18) of patients. One case report described an incident in which sudden intra-articular cement leakage led to a covering of part of the femoral head. Subsequent chondrolysis in 75% of the joint space required total hip replacement at 12 weeks. Transient worsening of pain was recorded in 73% (8/11) of patients in one study. Other reported complications included fever (below 39°C) following the intervention in 45% (5/11) of patients and an increase in serum creatinine levels in 9% (1/11) of patients. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers noted that theoretical adverse events may include death from cement venous embolus, and nerve or vascular injury as a result of local cement leakage. Pathological fractures may occur. Infection, bleeding and thermal damage caused by the cement are additional concerns. One Specialist Adviser noted that heat produced as the cement hardens may cause damage to neural structures. # Other comments It was noted that the procedure has also been used to treat benign bone lesions such as cysts, but very little data were available. It was noted that a variety of types of cement are available.# Further information NICE has issued interventional procedure guidance on percutaneous vertebroplasty. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the interventional procedure overview of percutaneous cementoplasty. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': 'Current evidence on the safety and efficacy of percutaneous cementoplasty for the palliative treatment of bony malignancies is limited, but appears adequate to support the use of this procedure in patients for whom other treatments have failed, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nPatient selection should be carried out in the context of a multidisciplinary team, which may include specialists in radiology, oncology, radiotherapy, orthopaedics, pain management and palliative care.', 'The procedure': "# Indications\n\nRadiotherapy is commonly used to treat patients with painful bony malignancy, although pain may not be relieved for up to 2 weeks after the procedure. Conservative therapy involves analgesia (often with narcotic drugs) and bed rest. However, in some patients, pain remains refractory to both pharmacological and radiation treatment.\n\nPercutaneous cementoplasty is indicated for patients with painful bone metastases resulting from tumours elsewhere in the body or, less frequently, with primary bone tumours. The aim of the procedure is to reduce pain and stabilise bones. Cementoplasty is the generic term for this procedure. Its use in vertebrae is commonly termed vertebroplasty (see section 3.1), and when treating the sacrum it may be described as sacroplasty.\n\n# Outline of the procedure\n\nPercutaneous cementoplasty involves the injection of acrylic bone cement into malignant bone cavities in order to relieve pain or stabilise the bone, or both.\n\nPercutaneous cementoplasty may be performed under general anaesthesia or, more commonly, using conscious sedation and local anaesthesia. A small skin incision is made and a 10–12-gauge trocar or needle is passed into the bone under fluoroscopic guidance.\n\nCement containing a radiopaque agent is used for this procedure. Visualisation of the cement during injection via multi-plane fluoroscopy is essential in order to limit extra-osseous leakage of cement. If leakage outside the bone occurs, the injection is halted while the cement hardens and plugs the leak, or for the needle to be repositioned.\n\nOnce the procedure is complete, the patient should remain recumbent and should not bear weight while the cement hardens.\n\n# Efficacy\n\nIn 14 patients in a case series, pain scores (measured using a self-reported visual analogue scale) improved from a mean 8.8 points at baseline to 1.9 points after cementoplasty (p < 0.0016). In another two studies, good pain relief was achieved in 82% (9/11) and 93% (13/14) of patients. In another case series, 22% (4/18) of patients had 'total improvement' in pain (no pain without analgesics), while 39% (7/18) had clear improvement at 72-hour follow-up.\n\nTwo studies reported mobility outcomes. One reported overall improvements in mobility in 93% (13/14) of patients at 1-week follow-up; the other study of 18 patients reported an improvement in mean walking score (on a 0–4 scale) from 1.1 at baseline to 2.1 at 1-month follow-up.\n\nThe evaluation of technical success varied across the studies. In one case series, cementoplasty was considered technically successful in all 14 patients; in another, good filling was demonstrated on postoperative computed tomography scans in 39% (7/18) of patients. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers noted that the procedure was a variation on the existing technique of vertebroplasty.\n\n# Safety\n\nAmong four case series, leakage of injected cement was reported in 6% (1/18), 14% (2/14), 27% (3/11) and 50% (9/18) of patients, although the definition of leakage varied between studies. Symptoms relating to cement leakage were reported in between 6% (1/18) and 11% (2/18) of patients. One case report described an incident in which sudden intra-articular cement leakage led to a covering of part of the femoral head. Subsequent chondrolysis in 75% of the joint space required total hip replacement at 12 weeks.\n\nTransient worsening of pain was recorded in 73% (8/11) of patients in one study. Other reported complications included fever (below 39°C) following the intervention in 45% (5/11) of patients and an increase in serum creatinine levels in 9% (1/11) of patients. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers noted that theoretical adverse events may include death from cement venous embolus, and nerve or vascular injury as a result of local cement leakage. Pathological fractures may occur. Infection, bleeding and thermal damage caused by the cement are additional concerns. One Specialist Adviser noted that heat produced as the cement hardens may cause damage to neural structures.\n\n# Other comments\n\nIt was noted that the procedure has also been used to treat benign bone lesions such as cysts, but very little data were available.\n\nIt was noted that a variety of types of cement are available.", 'Further information': 'NICE has issued interventional procedure guidance on percutaneous vertebroplasty.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the interventional procedure overview of percutaneous cementoplasty.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg179
8d91d874a28ac40bbeaf9f4fe755092d11bd1858	nice	Percutaneous laser therapy for fetal tumours	Percutaneous laser therapy for fetal tumours # Guidance Current evidence on the safety and efficacy of percutaneous laser therapy for fetal tumours does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake percutaneous laser therapy for fetal tumours should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that parents understand the uncertainty about the procedure's safety and efficacy. Clinicians should provide parents with clear written information and counselling support, both before and after the procedure. In addition, use of the NICE's information for the public is recommended. Audit and review clinical outcomes of all patients undergoing percutaneous laser therapy for fetal tumours. This procedure should only be performed in centres specialising in invasive fetal medicine and in the context of a multidisciplinary team that includes a consultant in fetal medicine, a midwife, a neonatologist and a paediatric surgeon. Data on all procedures should be entered onto the European Commission registry, which is endorsed by the British Maternal and Fetal Medicine Society. Publication of safety and efficacy outcomes will be useful. NICE may review the procedure on publication of further evidence.# The procedure # Indications Congenital cystic adenomatoid malformations (CCAM) are usually benign tumours, although sacrococcygeal teratomas may be malignant. These tumours can become very large and highly vascular, causing stress on the heart of the fetus. They can lead to the development of non-immune hydrops fetalis (in utero heart failure) and may be complicated by polyhydramnios (excessive accumulation of amniotic fluid). Non-immune hydrops fetalis, placentomegaly, cardiomegaly, large tumour size and high tumour growth rate are associated with poor prognosis, and fetal mortality is high. Obstetric complications include preterm labour and dystocia. The current options in managing pregnancies with these fetal tumours are: termination of the pregnancy; continuation of the pregnancy without intervention; interventional treatments such as alcohol sclerosis or cyst drainage; and early elective caesarean delivery if significant problems develop. In the latter case, the prognosis is poor even when the fetus is approaching term. # Outline of the procedure Percutaneous laser therapy for fetal tumours is performed under maternal local anaesthesia and light sedation. A needle is inserted through the mother's abdomen into the uterine cavity under ultrasonographic guidance. An analgesic is then injected subcutaneously or intramuscularly into the fetus, before advancing the needle to the site of the tumour. Colour Doppler imaging is used to guide placement of the needle. A laser fibre is passed through the needle lumen and laser energy is delivered in pulses, causing the blood vessels within the tumour to coagulate. If necessary, laser therapy can be repeated in a further session, usually 1 or more weeks later. Cystic components of tumours may be aspirated during the procedure. # Efficacy The efficacy and safety of the procedure are based on reports on seven fetuses: two with CCAM and five with sacrococcygeal teratoma. In a case series of 29 fetuses with sacrococcygeal teratomas, four were treated by percutaneous laser therapy; there were two intrauterine fetal deaths, one neonatal death and one live birth. In a case series of 67 fetuses diagnosed with cystic lung abnormalities, one fetus with CCAM received two percutaneous laser treatments. Reductions in non-immune hydrops fetalis, mediastinal shift, ascites and blood flow within the tumour were reported following the first treatment. The neonate was delivered at 38 weeks' gestation; surgical excision of the tumour was performed after birth. In one case report, a fetus with CCAM received two percutaneous laser treatments, both of which had to be terminated early because of fetal bradycardia. Reduction in tumour size was reported following the first treatment. No outcomes were reported following the second treatment. In another case report, a fetus with sacrococcygeal teratoma received two percutaneous laser treatments. The neonate was delivered by elective caesarean section at 37 weeks' gestation and the tumour was surgically excised after birth. The baby was reported to be healthy and developing normally at 8 months of age. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers stated that there is uncertainty about the effectiveness of the procedure. Key efficacy outcomes include a decrease in the vascularity of the fetal tumour, leading to potential shrinkage of the tumour in utero, and reduction in cardiac failure in the fetus. # Safety In the case series of 67 fetuses with cystic lung abnormalities, the fetus who received two percutaneous laser treatments died 4 days after birth from sepsis-related complications. In the case report of a fetus with CCAM, worsening of non-immune hydrops fetalis was reported 4 days after the first treatment. Three days after the second treatment (at a scheduled visit), the fetus was found to have died. In another case report of a fetus with sacrococcygeal teratoma, bleeding (possibly within the cystic area) occurred following the first treatment, requiring intrauterine blood transfusion. Drainage of blood from the cystic area and drainage of amniotic fluid were performed during the second treatment. For more details, refer to the 'Sources of evidence' section. The Specialist Advisers stated that theoretical risks include haemorrhage and procedure-related fetal death. There are also uncertainties about the potentially harmful effects of the procedure on other anatomical areas. The theoretical risks to the mother include preterm labour following the procedure, and laser burn if the needle is not sited correctly. # Other comments It was noted that the procedure might also be used to treat other fetal tumours such as cystic hygromas.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedure overview of percutaneous laser therapy for fetal tumours, October 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of percutaneous laser therapy for fetal tumours does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake percutaneous laser therapy for fetal tumours should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that parents understand the uncertainty about the procedure's safety and efficacy. Clinicians should provide parents with clear written information and counselling support, both before and after the procedure. In addition, use of the NICE's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients undergoing percutaneous laser therapy for fetal tumours.\n\nThis procedure should only be performed in centres specialising in invasive fetal medicine and in the context of a multidisciplinary team that includes a consultant in fetal medicine, a midwife, a neonatologist and a paediatric surgeon.\n\nData on all procedures should be entered onto the European Commission registry, which is endorsed by the British Maternal and Fetal Medicine Society.\n\nPublication of safety and efficacy outcomes will be useful. NICE may review the procedure on publication of further evidence.", 'The procedure': "# Indications\n\nCongenital cystic adenomatoid malformations (CCAM) are usually benign tumours, although sacrococcygeal teratomas may be malignant. These tumours can become very large and highly vascular, causing stress on the heart of the fetus. They can lead to the development of non-immune hydrops fetalis (in utero heart failure) and may be complicated by polyhydramnios (excessive accumulation of amniotic fluid). Non-immune hydrops fetalis, placentomegaly, cardiomegaly, large tumour size and high tumour growth rate are associated with poor prognosis, and fetal mortality is high. Obstetric complications include preterm labour and dystocia.\n\nThe current options in managing pregnancies with these fetal tumours are: termination of the pregnancy; continuation of the pregnancy without intervention; interventional treatments such as alcohol sclerosis or cyst drainage; and early elective caesarean delivery if significant problems develop. In the latter case, the prognosis is poor even when the fetus is approaching term.\n\n# Outline of the procedure\n\nPercutaneous laser therapy for fetal tumours is performed under maternal local anaesthesia and light sedation. A needle is inserted through the mother's abdomen into the uterine cavity under ultrasonographic guidance. An analgesic is then injected subcutaneously or intramuscularly into the fetus, before advancing the needle to the site of the tumour. Colour Doppler imaging is used to guide placement of the needle. A laser fibre is passed through the needle lumen and laser energy is delivered in pulses, causing the blood vessels within the tumour to coagulate. If necessary, laser therapy can be repeated in a further session, usually 1 or more weeks later. Cystic components of tumours may be aspirated during the procedure.\n\n# Efficacy\n\nThe efficacy and safety of the procedure are based on reports on seven fetuses: two with CCAM and five with sacrococcygeal teratoma.\n\nIn a case series of 29\xa0fetuses with sacrococcygeal teratomas, four were treated by percutaneous laser therapy; there were two intrauterine fetal deaths, one neonatal death and one live birth.\n\nIn a case series of 67\xa0fetuses diagnosed with cystic lung abnormalities, one fetus with CCAM received two percutaneous laser treatments. Reductions in non-immune hydrops fetalis, mediastinal shift, ascites and blood flow within the tumour were reported following the first treatment. The neonate was delivered at 38\xa0weeks' gestation; surgical excision of the tumour was performed after birth.\n\nIn one case report, a fetus with CCAM received two percutaneous laser treatments, both of which had to be terminated early because of fetal bradycardia. Reduction in tumour size was reported following the first treatment. No outcomes were reported following the second treatment.\n\nIn another case report, a fetus with sacrococcygeal teratoma received two percutaneous laser treatments. The neonate was delivered by elective caesarean section at 37\xa0weeks' gestation and the tumour was surgically excised after birth. The baby was reported to be healthy and developing normally at 8\xa0months of age. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers stated that there is uncertainty about the effectiveness of the procedure. Key efficacy outcomes include a decrease in the vascularity of the fetal tumour, leading to potential shrinkage of the tumour in utero, and reduction in cardiac failure in the fetus.\n\n# Safety\n\nIn the case series of 67 fetuses with cystic lung abnormalities, the fetus who received two percutaneous laser treatments died 4\xa0days after birth from sepsis-related complications.\n\nIn the case report of a fetus with CCAM, worsening of non-immune hydrops fetalis was reported 4\xa0days after the first treatment. Three days after the second treatment (at a scheduled visit), the fetus was found to have died.\n\nIn another case report of a fetus with sacrococcygeal teratoma, bleeding (possibly within the cystic area) occurred following the first treatment, requiring intrauterine blood transfusion. Drainage of blood from the cystic area and drainage of amniotic fluid were performed during the second treatment. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisers stated that theoretical risks include haemorrhage and procedure-related fetal death. There are also uncertainties about the potentially harmful effects of the procedure on other anatomical areas. The theoretical risks to the mother include preterm labour following the procedure, and laser burn if the needle is not sited correctly.\n\n# Other comments\n\nIt was noted that the procedure might also be used to treat other fetal tumours such as cystic hygromas.", 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedure overview of percutaneous laser therapy for fetal tumours, October\xa02005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg180
bb976fe2589af3bf9cbbdf77c4ea8e1df3470c3d	nice	Living-donor lung transplantation for end-stage lung disease	Living-donor lung transplantation for end-stage lung disease # Guidance Current evidence on the efficacy of living-donor lung transplantation for end-stage lung disease and its safety profile for suitable recipients appears adequate to support the use of this procedure. The procedure should only be used in selected patients who would otherwise die. However, limited evidence suggests that living-donor lung transplantation for end-stage lung disease carries a significant risk of morbidity for donors. Therefore clinicians wishing to undertake this procedure should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that donors receive thorough physical and psychological screening, and counselling about the morbidity associated with this procedure. They should also be provided with clear written information. In addition, use of NICE's information for the public is recommended. Audit and review clinical outcomes of all people donating lungs for transplantation. Living-donor lung transplantation for end-stage lung disease should only be performed in specialist centres in the context of a multidisciplinary team. Donor lungs should be harvested by specialist thoracic surgeons. Clinicians should enter all donors and recipients into the UK National Audit of Intrathoracic Transplantation.# The procedure # Indications Lung transplants are performed in patients with non-malignant pulmonary disease that is unresponsive or minimally responsive to treatment and who have a life expectancy of less than a year. The underlying causes include cystic fibrosis, severe pulmonary fibrosis, pulmonary hypertension and obliterative bronchiolitis. The majority of live-donor lung recipients are patients with cystic fibrosis. The majority of lung donors are first-degree relatives who are compatible in terms of size and ABO blood group. Living donation is an alternative to cadaveric organ donation. Living donation is an option for patients for whom cadaveric transplantation is unavailable, or who are deteriorating clinically to the point of transplant ineligibility while waiting for a cadaveric donor. Living donation may also be an option for critically ill children, as there is a particular shortage of suitable cadaveric donors for this age group. # Outline of the procedure Living-donor lung transplantation requires three operations: two donor lobectomies (one donor providing the right lower lobe and another, the left), and the recipient bilateral pneumonectomy and lung implant. The recipient operation is performed through a chest incision. Procedures are performed on cardiopulmonary bypass. Once the pneumonectomies have been completed the harvested lobes are implanted sequentially. # Efficacy In a study of 123 adult and paediatric patients who had undergone living lung transplantation, 1-, 3- and 5-year survival was 70%, 54% and 45%, respectively. Infection was the main cause of death (33/63; 52%), followed by obliterative bronchiolitis (8/63; 13%). In a non-randomised study from the same centre outcomes were compared between living (n = 59) and cadaveric (n = 43) lung recipients who had survived more than 3 months after transplant. The study found no significant differences between the groups with respect to survival; 1-, 3- and 5-year survival was 83%, 64% and 62%, respectively, in the living lung group compared with 83%, 81% and 75% in the cadaveric lung group. A true comparative analysis is difficult, however, because those receiving living lung transplants often have poorer outcomes by nature of eligibility criteria (for example, underlying lung disease and preoperative severity of illness). Where pulmonary function was measured in the studies it was reported that patients who had undergone living lung transplantation had improved function compared with preoperative values. For more details, refer to the 'Sources of evidence' section. Some Specialist Advisors expressed uncertainties about the long-term outcomes of recipients following living lung transplantation and the incidence of obliterative bronchiolitis compared with those undergoing cadaveric lung transplantation. # Safety There was limited information reported on the complications in recipients following living lung transplantation. In the studies that included both adult and paediatric patients, the incidence of acute rejection ranged from 0.8 to 1.5 episodes per patient. In a small study of 30 patients, complications following living lung transplantation included pulmonary oedema in 20% (6/30), haemorrhage necessitating rethoracotomy in 7% (2/30) and cardiac tamponade in 7% (2/30). Tracheostomy was required in 15 patients (50%), and reintubation in seven patients (23%). There were no reports of donor mortality following lobectomy. In one study it was reported that 20% (50/253) of donors had one or more perioperative complications following lobectomy. The most common complication was the need for a thoracostomy tube in 30% (15/50), either for persistent drainage or for air leaks. The most significant complication was pulmonary artery thrombosis, which occurred in two patients (1%). Eight patients (3%) also required reoperation because of bleeding (1.2%), bronchopulmonary fistula (0.4%), unresponsive pericarditis (0.4%), loculated pleural effusion (0.4%), a sterile empyema (0.4%) and a retained sponge (0.4%). In a study following 253 donor lobectomies it was reported that donors who could be contacted at 1 and 2 years had reduced pulmonary function compared with preoperative values. For more details, refer to the 'Sources of evidence' section. The Specialist Advisors considered the main complications in recipients to be rejection and hyperexpansion of the transplants leading to significant lung injury and subsequent failure. With respect to donors, the Specialist Advisors listed potential complications following donor lobectomy as prolonged air leak, bleeding, pleural sepsis and pulmonary embolism. The Specialist Advisors also stated that donors were likely to experience loss of lung function following lobectomy.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the interventional procedure overview of living donor lung transplant for end-stage lung disease. # Information for patients NICE has produced information on this procedure for the public. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the efficacy of living-donor lung transplantation for end-stage lung disease and its safety profile for suitable recipients appears adequate to support the use of this procedure.\n\nThe procedure should only be used in selected patients who would otherwise die.\n\nHowever, limited evidence suggests that living-donor lung transplantation for end-stage lung disease carries a significant risk of morbidity for donors. Therefore clinicians wishing to undertake this procedure should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that donors receive thorough physical and psychological screening, and counselling about the morbidity associated with this procedure. They should also be provided with clear written information. In addition, use of NICE's information for the public is recommended.\n\nAudit and review clinical outcomes of all people donating lungs for transplantation.\n\nLiving-donor lung transplantation for end-stage lung disease should only be performed in specialist centres in the context of a multidisciplinary team. Donor lungs should be harvested by specialist thoracic surgeons.\n\nClinicians should enter all donors and recipients into the UK National Audit of Intrathoracic Transplantation.", 'The procedure': "# Indications\n\nLung transplants are performed in patients with non-malignant pulmonary disease that is unresponsive or minimally responsive to treatment and who have a life expectancy of less than a year. The underlying causes include cystic fibrosis, severe pulmonary fibrosis, pulmonary hypertension and obliterative bronchiolitis.\n\nThe majority of live-donor lung recipients are patients with cystic fibrosis. The majority of lung donors are first-degree relatives who are compatible in terms of size and ABO blood group.\n\nLiving donation is an alternative to cadaveric organ donation. Living donation is an option for patients for whom cadaveric transplantation is unavailable, or who are deteriorating clinically to the point of transplant ineligibility while waiting for a cadaveric donor. Living donation may also be an option for critically ill children, as there is a particular shortage of suitable cadaveric donors for this age group.\n\n# Outline of the procedure\n\nLiving-donor lung transplantation requires three operations: two donor lobectomies (one donor providing the right lower lobe and another, the left), and the recipient bilateral pneumonectomy and lung implant.\n\nThe recipient operation is performed through a chest incision. Procedures are performed on cardiopulmonary bypass. Once the pneumonectomies have been completed the harvested lobes are implanted sequentially.\n\n# Efficacy\n\nIn a study of 123 adult and paediatric patients who had undergone living lung transplantation, 1-, 3- and 5-year survival was 70%, 54% and 45%, respectively. Infection was the main cause of death (33/63; 52%), followed by obliterative bronchiolitis (8/63; 13%).\n\nIn a non-randomised study from the same centre outcomes were compared between living (n = 59) and cadaveric (n = 43) lung recipients who had survived more than 3 months after transplant. The study found no significant differences between the groups with respect to survival; 1-, 3- and 5-year survival was 83%, 64% and 62%, respectively, in the living lung group compared with 83%, 81% and 75% in the cadaveric lung group. A true comparative analysis is difficult, however, because those receiving living lung transplants often have poorer outcomes by nature of eligibility criteria (for example, underlying lung disease and preoperative severity of illness).\n\nWhere pulmonary function was measured in the studies it was reported that patients who had undergone living lung transplantation had improved function compared with preoperative values. For more details, refer to the 'Sources of evidence' section.\n\nSome Specialist Advisors expressed uncertainties about the long-term outcomes of recipients following living lung transplantation and the incidence of obliterative bronchiolitis compared with those undergoing cadaveric lung transplantation.\n\n# Safety\n\nThere was limited information reported on the complications in recipients following living lung transplantation. In the studies that included both adult and paediatric patients, the incidence of acute rejection ranged from 0.8 to 1.5 episodes per patient. In a small study of 30 patients, complications following living lung transplantation included pulmonary oedema in 20% (6/30), haemorrhage necessitating rethoracotomy in 7% (2/30) and cardiac tamponade in 7% (2/30). Tracheostomy was required in 15 patients (50%), and reintubation in seven patients (23%).\n\nThere were no reports of donor mortality following lobectomy. In one study it was reported that 20% (50/253) of donors had one or more perioperative complications following lobectomy. The most common complication was the need for a thoracostomy tube in 30% (15/50), either for persistent drainage or for air leaks. The most significant complication was pulmonary artery thrombosis, which occurred in two patients (1%). Eight patients (3%) also required reoperation because of bleeding (1.2%), bronchopulmonary fistula (0.4%), unresponsive pericarditis (0.4%), loculated pleural effusion (0.4%), a sterile empyema (0.4%) and a retained sponge (0.4%). In a study following 253 donor lobectomies it was reported that donors who could be contacted at 1 and 2 years had reduced pulmonary function compared with preoperative values. For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisors considered the main complications in recipients to be rejection and hyperexpansion of the transplants leading to significant lung injury and subsequent failure. With respect to donors, the Specialist Advisors listed potential complications following donor lobectomy as prolonged air leak, bleeding, pleural sepsis and pulmonary embolism. The Specialist Advisors also stated that donors were likely to experience loss of lung function following lobectomy.", 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the interventional procedure overview of living donor lung transplant for end-stage lung disease.\n\n# Information for patients\n\nNICE has produced information on this procedure for the public. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg170
9b88e424866d5ecd1254bdfff6eb2fe8b913ecee	nice	Laparoscopic helium plasma coagulation for the treatment of endometriosis	Laparoscopic helium plasma coagulation for the treatment of endometriosis Evidence-based recommendations on laparoscopic helium plasma coagulation for the treatment of endometriosis. This involves a minimally invasive procedure used to vaporise endometrial deposits. # Guidance This guidance replaces the previous guidance on laparoscopic helium plasma coagulation for the treatment of endometriosis (Interventional Procedures Guidance no. 54, March 2004). Current evidence suggests there are no major safety concerns associated with laparoscopic helium plasma coagulation for the treatment of endometriosis. However, evidence on efficacy does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake laparoscopic helium plasma coagulation for the treatment of endometriosis should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the efficacy of the procedure and provide them with clear written information. In addition, use of NICE's information for the public is recommended. Audit and review clinical outcomes of all women undergoing laparoscopic helium plasma coagulation for the treatment of endometriosis. Clinicians undertaking this procedure should have adequate training before performing the technique. The British Society for Gynaecological Endoscopy has produced standards for training. Publication of randomised controlled trials on the efficacy of this procedure will be useful. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Women with endometriosis have deposits of endometrial tissue (which is normally confined to the lining of the uterus) outside the uterus. Many women are asymptomatic, but others may experience pelvic pain, dyspareunia, dysmenorrhoea or infertility. In most women, endometriosis can be treated with analgesics and hormones. Women whose endometriosis does not respond may be offered minimally invasive surgery to excise or destroy the endometrial deposits, most commonly by electrocautery or laser through a laparoscope. Women with very severe symptoms may be offered more radical treatment involving hysterectomy and removal of the ovaries. # Outline of the procedure Laparoscopic helium plasma coagulation of endometriosis is a minimally invasive procedure used to vaporise endometrial deposits. A laparoscope is used to direct an ionised beam of helium gas at endometrial deposits to destroy them. # Efficacy The method of evaluating symptoms following the procedure varied between studies, making comparison difficult. Across three series, symptomatic relief was achieved in 49% (39/79), 72% (179/250) and 81% (17/21) of women at 3 months' follow-up. In another case series, continuing symptoms were reported in 38% (5/13) of women at 14 months' follow-up. Only 1 case series of 50 women, which included 9 women who presented with infertility and 15 who were both symptomatic and infertile, reported fertility outcomes: 44% (4/9) of the solely infertile group and 20% (3/15) of the women who were also symptomatic had conceived within 6 months of the procedure. In 1 case series, none of the 250 procedures had to be converted to open surgery, and there were no re-admissions after 3 months, whereas a repeat procedure was required in 16% (5/31) of women in another case series, in which the mean period to return to normal daily activities was 12 days. There was no long-term follow-up of women beyond 6 months in published case series. For more details, refer to the sources of evidence section. The Specialist Advisors noted that the procedure may cause less lateral burning than the diathermy technique, and may allow women to be treated on a day-case basis. # Safety Three series recorded no side effects or complications related to the procedure in a total of 130 women. After 3 months' follow-up of 250 cases, 1 case series reported no major postoperative complications and no surgical complications. For more details, refer to the sources of evidence section. The Specialist Advisors noted that theoretical adverse events include damage to normal tissue (as seen when other energy sources are used), bowel injury, haemorrhage, infection and, potentially, helium embolisation.# Further information # Sources of evidence The evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of laparoscopic helium plasma coagulation of endometriosis. # Information for patients NICE has produced information for patients and carers on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "This guidance replaces the previous guidance on laparoscopic helium plasma coagulation for the treatment of endometriosis (Interventional Procedures Guidance no. 54, March 2004).\n\nCurrent evidence suggests there are no major safety concerns associated with laparoscopic helium plasma coagulation for the treatment of endometriosis. However, evidence on efficacy does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake laparoscopic helium plasma coagulation for the treatment of endometriosis should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the efficacy of the procedure and provide them with clear written information. In addition, use of NICE's information for the public is recommended.\n\nAudit and review clinical outcomes of all women undergoing laparoscopic helium plasma coagulation for the treatment of endometriosis.\n\nClinicians undertaking this procedure should have adequate training before performing the technique. The British Society for Gynaecological Endoscopy has produced standards for training.\n\nPublication of randomised controlled trials on the efficacy of this procedure will be useful. The Institute may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nWomen with endometriosis have deposits of endometrial tissue (which is normally confined to the lining of the uterus) outside the uterus. Many women are asymptomatic, but others may experience pelvic pain, dyspareunia, dysmenorrhoea or infertility.\n\nIn most women, endometriosis can be treated with analgesics and hormones. Women whose endometriosis does not respond may be offered minimally invasive surgery to excise or destroy the endometrial deposits, most commonly by electrocautery or laser through a laparoscope. Women with very severe symptoms may be offered more radical treatment involving hysterectomy and removal of the ovaries.\n\n# Outline of the procedure\n\nLaparoscopic helium plasma coagulation of endometriosis is a minimally invasive procedure used to vaporise endometrial deposits. A laparoscope is used to direct an ionised beam of helium gas at endometrial deposits to destroy them.\n\n# Efficacy\n\nThe method of evaluating symptoms following the procedure varied between studies, making comparison difficult. Across three series, symptomatic relief was achieved in 49% (39/79), 72% (179/250) and 81% (17/21) of women at 3\xa0months' follow-up. In another case series, continuing symptoms were reported in 38% (5/13) of women at 14\xa0months' follow-up.\n\nOnly 1\xa0case series of 50\xa0women, which included 9\xa0women who presented with infertility and 15 who were both symptomatic and infertile, reported fertility outcomes: 44% (4/9) of the solely infertile group and 20% (3/15) of the women who were also symptomatic had conceived within 6\xa0months of the procedure.\n\nIn 1\xa0case series, none of the 250\xa0procedures had to be converted to open surgery, and there were no re-admissions after 3\xa0months, whereas a repeat procedure was required in 16% (5/31) of women in another case series, in which the mean period to return to normal daily activities was 12\xa0days. There was no long-term follow-up of women beyond 6\xa0months in published case series. For more details, refer to the sources of evidence section.\n\nThe Specialist Advisors noted that the procedure may cause less lateral burning than the diathermy technique, and may allow women to be treated on a day-case basis.\n\n# Safety\n\nThree series recorded no side effects or complications related to the procedure in a total of 130\xa0women. After 3\xa0months' follow-up of 250\xa0cases, 1\xa0case series reported no major postoperative complications and no surgical complications. For more details, refer to the sources of evidence section.\n\nThe Specialist Advisors noted that theoretical adverse events include damage to normal tissue (as seen when other energy sources are used), bowel injury, haemorrhage, infection and, potentially, helium embolisation.", 'Further information': '# Sources of evidence\n\nThe evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of laparoscopic helium plasma coagulation of endometriosis.\n\n# Information for patients\n\nNICE has produced information for patients and carers on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg171	Evidence-based recommendations on laparoscopic helium plasma coagulation for the treatment of endometriosis. This involves a minimally invasive procedure used to vaporise endometrial deposits.
93f8d3dca3edb183c6b793cc6f20a85554c6cd7b	nice	High dose rate brachytherapy in combination with external-beam radiotherapy for localised prostate cancer	High dose rate brachytherapy in combination with external-beam radiotherapy for localised prostate cancer # Guidance Current evidence on the safety and efficacy of high dose rate (HDR) brachytherapy in combination with external-beam radiotherapy for localised prostate cancer appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. A multidisciplinary team should be involved in the planning and use of this procedure.# The procedure # Indications Treatment options for prostate cancer depend on whether the disease is localised to the prostate gland. Current management options for localised prostate cancer include radiotherapy, radical prostatectomy, cryotherapy, high-intensity focused ultrasound and watchful waiting. Radiation therapy can take the form of either external-beam radiotherapy (EBRT) or brachytherapy. Brachytherapy can be given at either low or high dose rates. # Outline of the procedure HDR brachytherapy is a form of radiotherapy in which radiation delivery is targeted directly at the prostate gland via a radiation source that is temporarily implanted within the prostate, as opposed to an external source. This procedure is usually done under general anaesthesia but may be performed under local anaesthesia with sedation. Thin plastic tubes are inserted through the perineal skin behind the scrotum into the prostate gland. A radioactive source is then inserted into each tube. A computer controls how long the radioactive source remains in each of the tubes, so that the amount of radiation can be targeted effectively. This allows a higher dose to be given to the tumour tissue than to the urethra and rectum. The tubes are then removed, leaving no radioactive material in the prostate gland. # Efficacy In a matched case series, actuarial 5-year survival with HDR brachytherapy in combination with EBRT was found to be greater than with EBRT alone (86% versus 54%, respectively; p < 0.001). Across a number of case series, 5-year survival rates after HDR brachytherapy and EBRT were estimated to be 85%, 89% and 93%. In 1 series, 84% (42/50) of men survived to 7.2 years' follow-up. In another case series of 611 men, survival was calculated to be 65% at 10 years. Five-year biochemical control (assessed by measurement of prostate-specific antigen ) has been shown to be more common with HDR brachytherapy in combination with EBRT than with EBRT alone (67% versus 44%; p<0.001); 3-year biochemical control with HDR brachytherapy is similar to that with LDR brachytherapy (98% versus 97%, respectively). In 2 case series, overall 5-year biochemical control was found to be 77% and 82%, and in a third case series, 4-year biochemical control was found to be 75%. One series found that only 5% (2/42) of survivors at 7.2 years had a PSA level greater than 1 ng/ml. In another series, mean PSA fell from 10 ng/ml to 1.1 ng/ml, and in 85% (170/200) of men, the PSA nadir was below 1 ng/ml over 30 months' follow-up. In a case series that reported outcomes of prostate biopsy findings following HDR brachytherapy in combination with EBRT, there was no evidence of viable cancer in 86% (36/42) of men; however, the percentage of men with residual cancer may have been higher, given the limited sensitivity of the biopsy technique employed. For more details, refer to the sources of evidence section. The Specialist Advisors noted that the benefits of the procedure include improved biochemical and overall survival. # Safety The definitions used to measure potency outcomes following HDR brachytherapy varied across the studies included. In men who were potent at baseline, impotence occurred in 30% at 30 months, 45% at 3 years, 14% at 5 years and 76% (31/41) at 7 years. Urethral stricture (where it was reported separately from other urological complications) occurred in 1.5% (3/200), 4% (6/161) and 7% (17/230) of men. Early urinary incontinence was reported in 11% of men in the HDR arm of a comparative study, and incontinence had persisted in 5% of men at 3 years' follow-up. A case series recorded grade 2 to 3 incontinence in 3% (7/230) of men, but in another series this occurred in less than 1% (1/200) of men. Survival free of urinary incontinence was estimated to have been achieved in 86% of men at 5 years in a case series of 108 men. For more details, refer to the sources of evidence section. The Specialist Advisors noted that the procedure had reduced side effects compared with other treatments. They also noted that theoretical adverse events include urethritis; urethral stricture; proctitis; incontinence; acute retention; impotence; haematuria; haematospermia; bladder, rectal and sphincter injuries and rectourethral fistula. # Other comments These recommendations do not apply to HDR brachytherapy for localised prostate cancer when used as monotherapy (in other words, as the single primary treatment modality). The Committee was informed that use of the procedure as monotherapy is currently the subject of research studies. It was noted that a variety of radiation dosage schedules has been reported in the literature. The data were difficult to interpret because of the heterogeneous groups of men in the studies. It was noted that men with prostate cancer often die from unrelated causes.# Further information NICE has published cancer service guidance improving outcomes in urological cancers. NICE has issued interventional procedures guidance on low dose rate brachytherapy for localised prostate cancer, cryotherapy for recurrent prostate cancer, cryotherapy as a primary treatment for prostate cancer, laparoscopic radical prostatectomy and high-intensity focused ultrasound for prostate cancer. # Sources of evidence The evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of high dose rate brachytherapy for prostate cancer. # Information for patients NICE has produced information for the public on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Other NICE recommendations on brachytherapy Further recommendations have been made as part of the NICE guideline on prostate cancer: diagnosis and management, which was published in May 2019, as follows: Brachytherapy is not recommended for men with high-risk localised prostate cancer. Clinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available in the guideline. The interventional procedure guidance on high dose rate brachytherapy in combination with external-beam radiotherapy for localised prostate cancer remains current, and should be read in conjunction with the prostate cancer guideline.	{'Guidance': 'Current evidence on the safety and efficacy of high dose rate (HDR) brachytherapy in combination with external-beam radiotherapy for localised prostate cancer appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nA multidisciplinary team should be involved in the planning and use of this procedure.', 'The procedure': "# Indications\n\nTreatment options for prostate cancer depend on whether the disease is localised to the prostate gland. Current management options for localised prostate cancer include radiotherapy, radical prostatectomy, cryotherapy, high-intensity focused ultrasound and watchful waiting.\n\nRadiation therapy can take the form of either external-beam radiotherapy (EBRT) or brachytherapy. Brachytherapy can be given at either low or high dose rates.\n\n# Outline of the procedure\n\nHDR brachytherapy is a form of radiotherapy in which radiation delivery is targeted directly at the prostate gland via a radiation source that is temporarily implanted within the prostate, as opposed to an external source.\n\nThis procedure is usually done under general anaesthesia but may be performed under local anaesthesia with sedation. Thin plastic tubes are inserted through the perineal skin behind the scrotum into the prostate gland. A radioactive source is then inserted into each tube. A computer controls how long the radioactive source remains in each of the tubes, so that the amount of radiation can be targeted effectively. This allows a higher dose to be given to the tumour tissue than to the urethra and rectum. The tubes are then removed, leaving no radioactive material in the prostate gland.\n\n# Efficacy\n\nIn a matched case series, actuarial 5-year survival with HDR brachytherapy in combination with EBRT was found to be greater than with EBRT alone (86% versus 54%, respectively; p < 0.001). Across a number of case series, 5-year survival rates after HDR brachytherapy and EBRT were estimated to be 85%, 89% and 93%. In 1\xa0series, 84% (42/50) of men survived to 7.2\xa0years' follow-up. In another case series of 611 men, survival was calculated to be 65% at 10\xa0years.\n\nFive-year biochemical control (assessed by measurement of prostate-specific antigen [PSA]) has been shown to be more common with HDR brachytherapy in combination with EBRT than with EBRT alone (67% versus 44%; p<0.001); 3-year biochemical control with HDR brachytherapy is similar to that with LDR brachytherapy (98% versus 97%, respectively). In 2\xa0case series, overall 5-year biochemical control was found to be 77% and 82%, and in a third case series, 4-year biochemical control was found to be 75%. One series found that only 5% (2/42) of survivors at 7.2\xa0years had a PSA level greater than 1\xa0ng/ml. In another series, mean PSA fell from 10\xa0ng/ml to 1.1\xa0ng/ml, and in 85% (170/200) of men, the PSA nadir was below 1\xa0ng/ml over 30\xa0months' follow-up.\n\nIn a case series that reported outcomes of prostate biopsy findings following HDR brachytherapy in combination with EBRT, there was no evidence of viable cancer in 86% (36/42) of men; however, the percentage of men with residual cancer may have been higher, given the limited sensitivity of the biopsy technique employed. For more details, refer to the sources of evidence section.\n\nThe Specialist Advisors noted that the benefits of the procedure include improved biochemical and overall survival.\n\n# Safety\n\nThe definitions used to measure potency outcomes following HDR brachytherapy varied across the studies included. In men who were potent at baseline, impotence occurred in 30% at 30\xa0months, 45% at 3\xa0years, 14% at 5\xa0years and 76% (31/41) at 7\xa0years.\n\nUrethral stricture (where it was reported separately from other urological complications) occurred in 1.5% (3/200), 4% (6/161) and 7% (17/230) of men.\n\nEarly urinary incontinence was reported in 11% of men in the HDR arm of a comparative study, and incontinence had persisted in 5% of men at 3\xa0years' follow-up. A case series recorded grade 2 to 3 incontinence in 3% (7/230) of men, but in another series this occurred in less than 1% (1/200) of men.\n\nSurvival free of urinary incontinence was estimated to have been achieved in 86% of men at 5\xa0years in a case series of 108\xa0men. For more details, refer to the sources of evidence section.\n\nThe Specialist Advisors noted that the procedure had reduced side effects compared with other treatments. They also noted that theoretical adverse events include urethritis; urethral stricture; proctitis; incontinence; acute retention; impotence; haematuria; haematospermia; bladder, rectal and sphincter injuries and rectourethral fistula.\n\n# Other comments\n\nThese recommendations do not apply to HDR brachytherapy for localised prostate cancer when used as monotherapy (in other words, as the single primary treatment modality). The Committee was informed that use of the procedure as monotherapy is currently the subject of research studies.\n\nIt was noted that a variety of radiation dosage schedules has been reported in the literature.\n\nThe data were difficult to interpret because of the heterogeneous groups of men in the studies.\n\nIt was noted that men with prostate cancer often die from unrelated causes.", 'Further information': 'NICE has published cancer service guidance improving outcomes in urological cancers.\n\nNICE has issued interventional procedures guidance on low dose rate brachytherapy for localised prostate cancer, cryotherapy for recurrent prostate cancer, cryotherapy as a primary treatment for prostate cancer, laparoscopic radical prostatectomy and high-intensity focused ultrasound for prostate cancer.\n\n# Sources of evidence\n\nThe evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of high dose rate brachytherapy for prostate cancer.\n\n# Information for patients\n\nNICE has produced information for the public on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.', 'Other NICE recommendations on brachytherapy': 'Further recommendations have been made as part of the NICE guideline on prostate cancer: diagnosis and management, which was published in May 2019, as follows:\n\nBrachytherapy is not recommended for men with high-risk localised prostate cancer.\n\nClinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available in the guideline. The interventional procedure guidance on high dose rate brachytherapy in combination with external-beam radiotherapy for localised prostate cancer remains current, and should be read in conjunction with the prostate cancer guideline.'}	https://www.nice.org.uk/guidance/ipg174
bec5adad9b28d159629e55caf224454336569853	nice	Percutaneous fetal balloon valvuloplasty for pulmonary atresia with intact ventricular septum	Percutaneous fetal balloon valvuloplasty for pulmonary atresia with intact ventricular septum # Guidance Current evidence on the safety and efficacy of percutaneous fetal balloon valvuloplasty for pulmonary atresia with intact ventricular septum does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake percutaneous fetal balloon valvuloplasty for pulmonary atresia with intact ventricular septum should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that parents understand the uncertainty about the procedure's safety and efficacy. Clinicians should provide parents with clear written information, and with counselling and support both before and after the procedure. In addition, use of NICE's information for the public is recommended. Audit and review the clinical outcomes of percutaneous fetal balloon valvuloplasty for pulmonary atresia with intact ventricular septum. This procedure should only be performed in centres specialising in invasive fetal medicine and in the context of a multidisciplinary team including a consultant in fetal medicine, a paediatric cardiologist, a neonatologist, a specialist midwife and a paediatric cardiac surgeon. An intention-to-treat registry has been developed by the Association for European Paediatric and Congenital Cardiology, and clinicians are encouraged to enter all cases into this registry. Further publication on the criteria for selecting patients for this procedure rather than treating them conservatively until delivery will be useful. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Congenital heart defects are the most common type of birth defect and include critical pulmonary stenosis, pulmonary atresia with a ventricular septal defect and pulmonary atresia with intact ventricular septum (PAIVS). In pulmonary atresia the pulmonary valve orifice is completely closed, thereby obstructing the outflow of blood from the heart to the lungs. Before birth oxygenated blood can still reach the systemic circulation by passing through the foramen ovale and any ventricular septal defect (VSD) to the left side of the heart. After birth the foramen ovale, VSD and ductus arteriosus must remain open to allow blood to pass to the lungs to become oxygenated. In PAIVS the absence of blood flow at ventricular level can result in severe hypoxia soon after birth if the flow through the foramen ovale and ductus arteriosus are not maintained. PAIVS is associated with underdevelopment of the tricuspid valve and the right ventricle but relatively normal growth of the pulmonary vessels and vascular bed. About 3% of fetuses with PAIVS will die in utero from hydrops. Severe cases of PAIVS are rare but carry a high rate of postnatal morbidity and mortality. Many fetuses diagnosed with PAIVS will survive until birth, and treatment is then possible. About 50% of children with PAIVS have a functional biventricular heart, and overall survival from birth to 5 years is about 85%. Given the complex staged open cardiac surgery that some infants and children will require, some parents will request termination of pregnancy. For babies born with PAIVS a staged approach to treatment is undertaken. Postnatal balloon valvuloplasty is the preferred option initially to encourage remodelling and growth of the right ventricle. Further balloon valvuloplasty is often required with later valve replacement. If balloon valvuloplasty is unsuccessful then open cardiac surgical options are available. The aim of fetal pulmonary balloon valvuloplasty is to prevent progressive damage to the ventricular muscle in utero, the development of hydrops and subsequent fetal death. This may also allow a greater chance of surgical success postnatally along with the preservation of a biventricular heart. Fetal pulmonary balloon valvuloplasty may be considered where there is a high risk of deterioration before delivery, with an increased likelihood of postnatal mortality or morbidity. Improvements in fetal imaging have assisted in the identification of suitable cases. # Outline of the procedure Fetal pulmonary balloon valvuloplasty is performed at 21 to 32 weeks' gestation under maternal local anaesthesia and sedation, by inserting a needle through the mother's abdominal wall into the uterine cavity under ultrasound guidance. Fetal analgesic is then injected before advancing the needle through the fetal chest wall into the right ventricular infundibulum of the fetus. A guidewire is inserted through the needle and across the pulmonary valve. A balloon catheter is inserted and then inflated to dilate the stenotic valve. The catheter and needle are then withdrawn. Fetal positioning is critical for success of the procedure. # Efficacy There is limited published evidence on this procedure. The total number of reported cases in the published literature is less than 10 and the patients were highly selected and heterogeneous. The largest series reports on the outcomes of five fetuses following fetal pulmonary valvuloplasty. Technical success was achieved in three fetuses, with some improvements in fetal haemodynamics. All three children survived to have postnatal surgery and were alive at 2, 3 and 4.5 years, respectively. The 2 fetuses in whom the procedure failed were both delivered: one had surgery after birth, but both died in the newborn period. For more details, refer to the sources of evidence section. None of the studies specifically reported on maternal outcomes. The Specialist Advisors noted the lack of data on this procedure and the difficulty in basing judgements about efficacy purely on survival, when the condition is rare and patients are carefully selected for this procedure. Specialist Advisors also noted that the criteria for case selection are not yet clear. # Safety There is limited published evidence on this procedure. In one report of 2 fetuses, both had pericardial effusions that resolved spontaneously. There was also one instance of transient pericardial effusion in a report of 5 fetuses. None of the studies specifically reported on maternal outcomes. For more details, refer to the sources of evidence section. The Specialist Advisors listed fetal death, bleeding, bradycardia, pericardial effusion and balloon rupture as potential complications. They also noted that there was a risk of premature labour and possible maternal morbidity associated with the use of anaesthesia.# Further information NICE has published interventional procedures guidance on: balloon valvuloplasty for aortic valve stenosis in adults and children balloon dilatation of pulmonary valve stenosis balloon angioplasty of pulmonary vein stenosis in infants balloon dilatation with or without stenting for pulmonary artery or non-valvar right ventricular outflow tract obstruction in children balloon dilatation of systemic to pulmonary arterial shunts in children radiofrequency valvotomy for pulmonary atresia and percutaneous balloon valvuloplasty for fetal critical aortic stenosis. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the interventional procedure overview of percutaneous fetal pulmonary balloon valvuloplasty for pulmonary atresia with intact ventricular septum (PAIVS). # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of percutaneous fetal balloon valvuloplasty for pulmonary atresia with intact ventricular septum does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake percutaneous fetal balloon valvuloplasty for pulmonary atresia with intact ventricular septum should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that parents understand the uncertainty about the procedure's safety and efficacy. Clinicians should provide parents with clear written information, and with counselling and support both before and after the procedure. In addition, use of NICE's information for the public is recommended.\n\nAudit and review the clinical outcomes of percutaneous fetal balloon valvuloplasty for pulmonary atresia with intact ventricular septum.\n\nThis procedure should only be performed in centres specialising in invasive fetal medicine and in the context of a multidisciplinary team including a consultant in fetal medicine, a paediatric cardiologist, a neonatologist, a specialist midwife and a paediatric cardiac surgeon.\n\nAn intention-to-treat registry has been developed by the Association for European Paediatric and Congenital Cardiology, and clinicians are encouraged to enter all cases into this registry.\n\nFurther publication on the criteria for selecting patients for this procedure rather than treating them conservatively until delivery will be useful. The Institute may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nCongenital heart defects are the most common type of birth defect and include critical pulmonary stenosis, pulmonary atresia with a ventricular septal defect and pulmonary atresia with intact ventricular septum (PAIVS). In pulmonary atresia the pulmonary valve orifice is completely closed, thereby obstructing the outflow of blood from the heart to the lungs. Before birth oxygenated blood can still reach the systemic circulation by passing through the foramen ovale and any ventricular septal defect (VSD) to the left side of the heart. After birth the foramen ovale, VSD and ductus arteriosus must remain open to allow blood to pass to the lungs to become oxygenated. In PAIVS the absence of blood flow at ventricular level can result in severe hypoxia soon after birth if the flow through the foramen ovale and ductus arteriosus are not maintained.\n\nPAIVS is associated with underdevelopment of the tricuspid valve and the right ventricle but relatively normal growth of the pulmonary vessels and vascular bed. About 3% of fetuses with PAIVS will die in utero from hydrops. Severe cases of PAIVS are rare but carry a high rate of postnatal morbidity and mortality.\n\nMany fetuses diagnosed with PAIVS will survive until birth, and treatment is then possible. About 50% of children with PAIVS have a functional biventricular heart, and overall survival from birth to 5\xa0years is about 85%. Given the complex staged open cardiac surgery that some infants and children will require, some parents will request termination of pregnancy.\n\nFor babies born with PAIVS a staged approach to treatment is undertaken. Postnatal balloon valvuloplasty is the preferred option initially to encourage remodelling and growth of the right ventricle. Further balloon valvuloplasty is often required with later valve replacement. If balloon valvuloplasty is unsuccessful then open cardiac surgical options are available.\n\nThe aim of fetal pulmonary balloon valvuloplasty is to prevent progressive damage to the ventricular muscle in utero, the development of hydrops and subsequent fetal death. This may also allow a greater chance of surgical success postnatally along with the preservation of a biventricular heart.\n\nFetal pulmonary balloon valvuloplasty may be considered where there is a high risk of deterioration before delivery, with an increased likelihood of postnatal mortality or morbidity. Improvements in fetal imaging have assisted in the identification of suitable cases.\n\n# Outline of the procedure\n\nFetal pulmonary balloon valvuloplasty is performed at 21 to 32 weeks' gestation under maternal local anaesthesia and sedation, by inserting a needle through the mother's abdominal wall into the uterine cavity under ultrasound guidance. Fetal analgesic is then injected before advancing the needle through the fetal chest wall into the right ventricular infundibulum of the fetus. A guidewire is inserted through the needle and across the pulmonary valve. A balloon catheter is inserted and then inflated to dilate the stenotic valve. The catheter and needle are then withdrawn.\n\nFetal positioning is critical for success of the procedure.\n\n# Efficacy\n\nThere is limited published evidence on this procedure. The total number of reported cases in the published literature is less than 10 and the patients were highly selected and heterogeneous. The largest series reports on the outcomes of five fetuses following fetal pulmonary valvuloplasty. Technical success was achieved in three fetuses, with some improvements in fetal haemodynamics. All three children survived to have postnatal surgery and were alive at 2, 3\xa0and 4.5\xa0years, respectively. The 2\xa0fetuses in whom the procedure failed were both delivered: one had surgery after birth, but both died in the newborn period. For more details, refer to the sources of evidence section.\n\nNone of the studies specifically reported on maternal outcomes.\n\nThe Specialist Advisors noted the lack of data on this procedure and the difficulty in basing judgements about efficacy purely on survival, when the condition is rare and patients are carefully selected for this procedure. Specialist Advisors also noted that the criteria for case selection are not yet clear.\n\n# Safety\n\nThere is limited published evidence on this procedure. In one report of 2\xa0fetuses, both had pericardial effusions that resolved spontaneously. There was also one instance of transient pericardial effusion in a report of 5\xa0fetuses.\n\nNone of the studies specifically reported on maternal outcomes. For more details, refer to the sources of evidence section.\n\nThe Specialist Advisors listed fetal death, bleeding, bradycardia, pericardial effusion and balloon rupture as potential complications. They also noted that there was a risk of premature labour and possible maternal morbidity associated with the use of anaesthesia.", 'Further information': 'NICE has published interventional procedures guidance on:\n\nballoon valvuloplasty for aortic valve stenosis in adults and children\n\nballoon dilatation of pulmonary valve stenosis\n\nballoon angioplasty of pulmonary vein stenosis in infants\n\nballoon dilatation with or without stenting for pulmonary artery or non-valvar right ventricular outflow tract obstruction in children\n\nballoon dilatation of systemic to pulmonary arterial shunts in children\n\nradiofrequency valvotomy for pulmonary atresia and\n\npercutaneous balloon valvuloplasty for fetal critical aortic stenosis.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the interventional procedure overview of percutaneous fetal pulmonary balloon valvuloplasty for pulmonary atresia with intact ventricular septum (PAIVS).\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg176
c0b6b3219eb2bde889f2482ea575a0d02e5632e9	nice	Capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer	Capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer Evidence-based recommendations on capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer in adults. # Guidance The following are recommended as options for the adjuvant treatment of patients with stage III (Dukes' C) colon cancer following surgery for the condition: capecitabine as monotherapy -xaliplatin in combination with 5-fluorouracil and folinic acid. The choice of adjuvant treatment should be made jointly by the individual and the clinicians responsible for treatment. The decision should be made after an informed discussion between the clinicians and the patient; this discussion should take into account contraindications and the side-effect profile of the agent(s) and the method of administration as well as the clinical condition and preferences of the individual.# Clinical need and practice Colon cancer is a malignant neoplasm arising from the lining (mucosa) of the large intestine (colon). Colorectal cancer (including cancers of the rectum as well as cancers of the colon) is the third most common cancer in the UK. Almost 30,000 new cases were registered in England and Wales in 2002, representing over 12% of all new cancer cases. The incidence of colorectal cancer increases with age. In people between the ages of 45 and 49 years the incidence is about 20 per 100,000. Among those aged 75 and above, the rate is over 300 per 100,000 per year for men and over 200 per 100,000 per year for women. In the UK, about 26% of patients diagnosed with colorectal cancer are classified as having stage III (or C1, C2 according to the modified Dukes' classification – patients whose tumour has spread to lymph nodes) disease at the time of presentation. These patients have an overall 5-year survival rate of between 25% and 60%. About two thirds of tumours develop in the colon and the remainder in the rectum. After a complete surgical resection (undertaken with curative intent), patients with stage III colon cancer have a 50–60% chance of developing recurrent disease. The 2004 NICE guidance on cancer services recommends that systemic chemotherapy should be offered to all patients who, after surgery for Dukes' stage C colon or rectal cancer, are fit enough to tolerate it; that a multidisciplinary team should ensure that adjuvant chemotherapy is scheduled to begin within 6 weeks of surgery; and that standard treatment is a 6-month course of 5-fluorouracil and folinic acid (5-FU/FA), given intravenously. 5-FU/FA can be given in regimens involving bolus doses or continuous infusions. In clinical trials of adjuvant chemotherapy for colon cancer, the outcome of treatment is usually reported in terms of disease-free survival. This is commonly defined as the time from randomisation to either the first relapse, a second primary colon cancer, death from any cause (with no evidence of relapse), or when the patient is disease free (censoring time). In some trials, relapse-free survival is used as a secondary outcome measure and is defined in the same way as disease-free survival, but excludes death unrelated to disease progression or treatment. Overall survival is also often reported as a secondary endpoint, but has disadvantages as an indicator of effectiveness. (In recurrent or advanced disease the activity of the adjuvant therapy may be masked by differences in subsequent therapy.) Pooled data suggest that 5-FU/FA regimens will increase disease-free survival at 5 years from 42% to 58%, and overall survival from 51% to 64%, when compared with surgery alone. National Institute for Clinical Excellence (2004). Improving outcomes in colorectal cancers: manual update. Guidance on cancer services.# The technologies # Capecitabine Capecitabine (Xeloda, Roche) is an orally administered precursor of the cytotoxic moiety 5-fluorouracil (5-FU). It is licensed for the adjuvant treatment of patients following surgery of stage III (Dukes' stage C) colon cancer, and for first-line monotherapy for metastatic colorectal cancer. Capecitabine is contraindicated in patients with severe leucopenia, neutropenia or thrombocytopenia, and in patients with severe hepatic impairment or severe renal impairment. Dose-limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and hand–foot syndrome (erythema and desquamation of the palms and the soles of the feet). Most adverse events are reversible and do not require permanent discontinuation of therapy, although doses may need to be withheld or reduced. For full details of side effects and contraindications, see the Summary of Product Characteristics. The cost of 60 x 150-mg tablets and 120 x 500-mg tablets of capecitabine is £44.47 and £295.06, respectively (excluding VAT; British National Formulary 50). For a person with a surface area of 1.75 m2 receiving the recommended dose, the cost of treatment with capecitabine is £301.46 per cycle. Costs may vary in different settings because of negotiated procurement discounts. # Oxaliplatin Oxaliplatin (Eloxatin, Sanofi-Aventis) is a water-soluble platinum-based cytotoxic drug that prevents DNA replication, and hence cell division, by cross-linking DNA. Oxaliplatin in combination with intravenous 5-FU/FA is licensed for adjuvant treatment of stage III (Dukes' C) colon cancer after complete resection of primary tumour, and for the treatment of metastatic colorectal cancer. Neurotoxic side effects can be dose limiting. Acute paraesthesias or dysaesthesias of the extremities, triggered or exacerbated by cold temperatures, occur in 85–95% of people within hours of oxaliplatin infusion. These symptoms are normally mild and resolve within hours or days. However, with increasing cumulative dose, peripheral sensory symptoms increase in duration and intensity. Symptoms may progress to functional impairment. Cumulative neurotoxicity is reversible in most, but not all, cases, with regression of symptoms occurring in 4–6 months in about 80% of patients (see also 4.1.13). Other side effects include gastrointestinal disturbances and myelosuppression. Oxaliplatin is contraindicated in patients who have myelosuppression before starting the first course, as evidenced by a baseline neutrophil count of less than 2 x 109 per litre and/or a platelet count of less than 100 x 109 per litre. It is also contraindicated in patients who have a peripheral neuropathy with functional impairment before the first course. For full details of side effects and contraindications, see the Summary of Product Characteristics. The recommended dose for oxaliplatin is 85 mg/m2 when given in combination with 5-FU/FA. It is administered as an intravenous infusion over 2–6 hours every 2 weeks (usually for 6 months) followed by an infusion of 5-FU/FA. Vials containing 50 mg and 100 mg cost £165 and £330, respectively (excluding VAT; BNF 50). For a person with a surface area of 1.75 m2 receiving the recommended dose, the cost of treatment with oxaliplatin is £495 per cycle. Costs may vary in different settings because of negotiated procurement discounts.# Evidence and interpretation The Appraisal Committee (Appendix A) considered evidence from a number of sources (Appendix B). # Clinical effectiveness ## Capecitabine One randomised, open-label, active-controlled trial with 1987 participants, the Xeloda – Adjuvant Chemotherapy Trial (X-ACT), investigated the efficacy and safety of capecitabine treatment versus 5-FU/FA treatment (bolus Mayo Clinic regimen) in the postoperative adjuvant setting in patients with stage III (Dukes' C) colon cancer. Apart from the protocol-specified analyses, ad hoc analyses were carried out at the request of the US Food and Drugs Administration (FDA). For the primary endpoint of disease-free survival, the study was powered to establish non-inferiority, defined so that the upper limit of the 95% confidence interval (CI) around the hazard ratio was no more than 1.25. The median age of participants was 62 years in the capecitabine arm and 63 years in the 5-FU/FA arm. After a median follow-up of 3.8 years, 35% of patients in the capecitabine arm had experienced disease recurrence (relapse or new occurrence of colon cancer) or died, compared with 39% in the 5-FU/FA arm. The hazard ratio for recurrence was 0.87 (95% CI, 0.75 to 1.00). Updated analyses, not specified in the protocol, showed that with longer follow-up (minimum 3 years and median 4.4 years) capecitabine remained at least as effective as 5-FU/FA. Overall survival data were not mature at the time of the primary (specified) and secondary (ad hoc) analyses. However, at 3.8 years median follow-up, 80% and 77% of patients were alive in the capecitabine and 5-FU/FA arms, respectively. Quality of life (QoL) was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), with global health status being the primary parameter for the QoL evaluation. In both treatment groups, scores for global health status were constant over time (from baseline to 25 weeks of trial treatment) and there were no major (statistically significant) differences between the two groups. Severe stomatitis and hair loss were significantly more common in the participants treated with 5-FU/FA. In addition, neutropenia, as a clinical adverse event requiring medical intervention, was significantly less common in participants treated with capecitabine. The only treatment-related adverse events occurring statistically significantly more frequently with capecitabine than with 5-FU/FA were hand–foot syndrome (p < 0.001) and hyperbilirubinaemia. A submission by a professional organisation reports that 'when given a choice, most cancer patients prefer oral instead of intravenous therapy, but only if the treatment is equally effective; patients cite increased convenience, less distress over repeated intravenous access and more control over their own treatment as major factors'. ## Oxaliplatin Two phase III, randomised active-controlled trials that compared oxaliplatin with standard treatment were identified by the Assessment Group. The first was the Multicenter International Study of Oxaliplatin/5-fluorouracil and leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) trial. (This was open-label and had 2246 participants – 60% with stage III and the remainder with stage II colon cancer.) The second trial was the National Surgical Adjuvant Breast and Bowel Project (NSABP C-07) trial. (This had 2492 participants – 71% with stage III and the remainder with stage II colon cancer.) The NSABP C-07 trial was only available in abstract form. In the MOSAIC trial, oxaliplatin was combined with 5-FU/FA in the de Gramont regimen (an infusional regimen) and compared with 5-FU/FA alone (also given in the de Gramont regimen). In the NSABP C-07 trial, standard treatment consisted of 5-FU/FA administered via a bolus regimen (Roswell Park) and this was subsequently compared with oxaliplatin in combination with the same bolus regimen. In addition to the protocol-specified analyses, ad hoc analyses were carried out at the request of the FDA in the MOSAIC trial. The median age of trial participants was 61 years and 60 years in the oxaliplatin plus 5-FU/FA and the 5-FU/FA alone groups, respectively. NSABP C-07 did not report age at baseline. QoL data were not routinely collected within either trial. In both trials the addition of oxaliplatin to 5-FU/FA, albeit administered via different regimens, led to a statistically significant reduction in rate of relapse when compared with 5-FU/FA monotherapy. Analysis of disease-free survival at 3 years showed a hazard ratio for recurrence of 0.77 (95% CI, 0.65 to 0.91) in the MOSAIC trial (median follow-up 37.9 months; intention to treat analysis), and 0.79 (95% CI, 0.67 to 0.93) in the NSABP C-07 trial (median follow-up 34 months, according to protocol analysis). Additional analyses on MOSAIC – requested by regulatory authorities – showed a 24% reduction in the rate of relapse (improved disease-free survival) at a median follow-up of 4 years (hazard ratio for recurrence 0.76; 95% CI, 0.65 to 0.90). Overall survival results for MOSAIC and NSABP C-07 are to be calculated at follow-up periods of 6 years and 5 years respectively. No mature data are available for MOSAIC at present, and the interim 3-year and 4-year analyses report no statistically significant differences in overall survival between the study groups; 88.2% and 87.0% still alive at 38 months in the oxaliplatin plus 5-FU/FA and the 5-FU/FA arms, respectively, and a hazard ratio for death of 0.89 (95% CI, 0.72 to 1.09) in the 4-year analysis favouring the addition of oxaliplatin. The abstract of the NSABP C-07 trial did not report overall survival. Only in the MOSAIC study were subgroups prespecified according to stage of the disease, with results reported separately. For participants with stage III colon cancer, the hazard ratio for recurrence was found to be 0.76 (95% CI, 0.62 to 0.92) at 3 years, and 0.75 (95% CI, 0.62 to 0.90) at 4 years. The percentages of people experiencing relapse or death in the oxaliplatin plus 5-FU/FA and the 5-FU/FA arms were 26.9% and 33.5%, respectively. The hazard ratio for death for stage III patients in MOSAIC was 0.86 (95% CI, 0.66 to 1.11) at 3 years. Although the MOSAIC study was adequately powered to demonstrate improved survival outcomes in patients with stage II (40% of total population) or III (60% of total population) disease, the study was not powered to detect a therapeutic effect by subgroup. In the MOSAIC trial more participants discontinued treatment because of adverse events in the oxaliplatin plus 5-FU/FA group (14.4%) than in the group receiving 5-FU/FA monotherapy (5.6%). Neutropenia and paraesthesia are the toxicities most reported for oxaliplatin plus 5-FU/FA. Grade 3 peripheral neuropathy was observed in 12.4% of patients during treatment (median number of cycles 12; equivalent to about 6 months of chemotherapy), and in 1.1% and 0.5% of patients at 12 months and 18 months follow-up, respectively. Other frequent adverse events in the oxaliplatin plus infusional 5-FU/FA group were diarrhoea, nausea and vomiting. Grade 3 neurotoxicity was observed in 8% of patients receiving oxaliplatin plus bolus 5-FU/FA in the NSABP C-07 trial compared with 1% of patients receiving 5-FU/FA alone. After 1 year of follow-up, grade 3 neuropathy in the oxaliplatin plus 5-FU/FA group remained in 0.5% of patients. The Assessment Group noted that the incidence of grade 3/4 diarrhoea in the combination arm was much higher than that observed in MOSAIC: approximately 40% and 11%, respectively. A joint submission by professional organisations reports that oxaliplatin causes a unique cold-related peripheral neuropathy affecting over 90% of patients during treatment, and that symptoms are still present to a greater or lesser degree 18 months after completing treatment in 24% of patients. Another submission by a professional group refers to the combined incidence of grade 2 and 3 neurosensory symptoms as reported in the MOSAIC trial. It notes that 18 months after completion of treatment, 3.9% of patients had persistent debilitating symptoms. ## Comparison of infusional and bolus regimes for 5-FU/FA Three randomised comparisons of bolus versus infusional regimens have been published. Only two studies followed individuals for 5 years – a suitable proxy for long-term survival. The evidence reviewed suggests that infusional intravenous 5-FU-based adjuvant therapy is equivalent to, but has relatively less toxicity than, traditional bolus 5-FU/FA in extending survival and QoL. However, there are concerns about catheter-associated complications, patient inconvenience and the cost of infusional treatment. In the adjuvant setting, the weekly intravenous bolus 5-FU/FA for 30 weeks (QUASAR regimen) is most commonly used in the NHS in England and Wales. However, there remains significant geographical variation in the 5-FU-based regimens currently in use in the UK. # Cost effectiveness The Assessment Group reviewed three published economic evaluations, two of which were submitted by manufacturers. It also presented its own three-state Markov model to estimate the cost effectiveness of oxaliplatin plus 5-FU/FA versus 5-FU/FA alone, and of capecitabine versus 5-FU/FA alone. In the Assessment Group model, hypothetical individuals were assumed to move between three states: alive without relapse, alive with relapse, and dead. Transition probabilities in the Assessment Group model and one of the manufacturer models were estimated from the disease-free survival curve and the partitioned overall survival curves for patients with and without relapse. This joint modelling of disease-free and overall survival differs from the approach adopted in the model submitted by the manufacturer of capecitabine, where there was independent modelling of relapse-free survival and overall survival with inconsistent results. Key assumptions used in the Assessment Group model were as follows. Overall survival of people who relapse is assumed to be independent of the time of relapse. Overall survival of people who relapse is equivalent to that of patients who are initially diagnosed with advanced (stage IV – Dukes' D) colorectal cancer. All relapses occur within the 5 years following resection of the primary tumour. Overall survival of people alive and disease free at 5 years is similar to the survival in the general population, adjusting for age and sex. People who relapse are assumed to receive first-line 5-FU/FA followed upon progression by single-agent irinotecan. People receiving 5-FU/FA via the de Gramont regimen are assumed to receive their treatment on an outpatient basis. All of these assumptions, except for the last two, are also used in the model submitted by the manufacturer of oxaliplatin. Instead of using the cost of a specific chemotherapy regimen to estimate cost of relapse, the manufacturer's model uses an average cost of relapse that is calculated from a distribution using costs of treatment for four different types of relapse. Evidence for estimating preference-based utilities for the different health states is scarce. The submissions from the manufacturers of both drugs based their utility estimates on a study of 173 patients with colorectal cancer (40 of whom had stage III disease). In this study, generic and cancer-specific QoL tools were administered at regular intervals following diagnosis, starting at 13 months post diagnosis. Although the study did not differentiate between patients who relapsed and those who did not, both submissions used a disutility of approximately 0.2 for people who experienced relapse. In the manufacturer submission for oxaliplatin, utilities while on treatment were also corrected for adverse events. The Assessment Group noted that because the study used in the manufacturers' submissions started long after diagnosis, and a relatively small proportion of patients had stage III disease, they could only use data from this study to estimate the utility for people in remission (0.92). From a second study that elicited utilities from 81 patients with colorectal cancer with all stages of the disease (including those with stage III undergoing resection and chemotherapy), utilities were taken for those people undergoing treatment without adverse events (0.7) and with adverse events (0.63), as well as for those who relapse (0.24). ## Capecitabine The key cost driver of the economic analysis submitted by the manufacturer was the difference in the drug acquisition and administration costs between the capecitabine and 5-FU/FA (Mayo Clinic regimen) arms. Acquisition costs were approximately £1400 higher for the capecitabine arm, whereas administration costs and costs associated with adverse events were lower for the capecitabine arm – approximately £4750 and £300 per patient for 5-FU/FA and capecitabine, respectively. Primarily because of reduced drug administration costs associated with capecitabine (long-term costs were assumed to be approximately equal), the manufacturer's submission concluded that capecitabine is cost saving compared with 5-FU/FA, costing on average £3653 less per patient. Combined with lifetime extrapolated relapse-free and overall survival benefits, treatment with capecitabine also leads to a gain of 0.75 quality-adjusted life years (QALYs) in the manufacturer's model. The one-way sensitivity analyses and extreme analysis showed that the only significant uncertain driver for varying cost effectiveness is the cost per administration visit. Scenario analyses on the regimen used for 5-FU/FA indicate that capecitabine remains cost saving whichever regimen is used. In the Assessment Group model, total cost savings from the use of capecitabine compared with the Mayo Clinic 5-FU/FA regimen are slightly less than those reported in the manufacturer's submission (£3320). This is primarily due to the differences between the two models in the costs associated with relapse and a difference in pharmacy costs between capecitabine and 5-FU/FA that was included in the Assessment Group model but not in the manufacturer's submission. The higher QALY gain associated with capecitabine in the Assessment Group model (0.98 QALYs) appears to be attributable to the different methods used to estimate survival. In all the one-way sensitivity analyses, capecitabine treatment results in a cost saving when compared with 5-FU/FA in the Mayo Clinic regimen. ## Oxaliplatin Two published economic analyses that considered oxaliplatin plus 5-FU/FA in the adjuvant setting were included in the Assessment Report. One of these analyses was conducted from a non-UK perspective and used survival estimates from trials of oxaliplatin plus 5-FU/FA in advanced colorectal cancer that are unlikely to be representative of survival outcomes for patients receiving adjuvant chemotherapy. Further analysis by the Assessment Group of the marginal cost and survival results given in the paper suggested that the cost per life year gained of the addition of oxaliplatin to 5-FU/FA is £24,952. An abstract of another economic analysis was presented at the 2005 meeting of the American Society of Clinical Oncology (ASCO) and updated to form the basis of the manufacturer's submission to the appraisal (see 4.2.11 below). The cost per life year gained associated with oxaliplatin plus infusional 5-FU/FA in this study was estimated to be US$27,300. The economic model submitted by the manufacturer was based on patient-level data from the MOSAIC trial. It used observed mortality and disease-free survival, as well as the relationship between disease-free survival and overall survival, to estimate the difference in overall survival between the two treatment arms. Data from MOSAIC that relate to the cohort of patients with stage III colon cancer were used to report a base-case cost per QALY gained (CQG) of £4805 for oxaliplatin plus infusional 5-FU/FA versus infusional 5-FU/FA alone, calculated over a 50-year time horizon. This CQG estimate consists of a difference in costs of £3267 and a difference in benefits of 0.68 QALYs. When a one-way sensitivity analysis was performed, and benefits and costs were limited to those within trial data, the CQG increased to £56,780. There was no other one-way sensitivity analysis that resulted in a very different estimate from that of the base case – not even a doubling of the disutility for relapse (to 0.4). The manufacturer suggests that the difference between its base-case results (for stage II and III combined – CQG of £7210) and those of the published economic analyses is probably due to the lower drug acquisition costs of oxaliplatin in the UK compared with the US. In an addendum to its submission the manufacturer presented a second cost-effectiveness analysis, now based on the NSABP C-07 trial. Equivalent efficacy (0.68 QALYs gained) was assumed for oxaliplatin plus bolus 5-FU/FA (Mayo Clinic regimen) and oxaliplatin plus 5-FU/FA (de Gramont). When combined with a cost difference of £4246 between oxaliplatin plus bolus 5-FU/FA (Mayo Clinic regimen) and 5-FU/FA alone (Mayo Clinic regimen), this analysis resulted in a CQG estimate of £6244 for oxaliplatin plus 5-FU/FA relative to 5-FU/FA alone. Incremental benefits in the Assessment Group model were greater than those in the manufacturer's submission (1.33 versus 0.68 QALYs) when oxaliplatin plus 5-FU/FA (de Gramont) was compared with 5-FU/FA alone (de Gramont). Reasons for this lie in the differences in methods used for long-term extrapolation of survival curves and utility estimates used for those people that relapse in the economic model. When incremental benefits were combined with a cost difference that was also greater than that in the manufacturer's submission (£3940), the Assessment Group model resulted in an estimated CQG of £2970. This cost difference arises because the manufacturer's model uses differential costs of relapse for the 5-FU/FA and combination arms, whereas the Assessment Group model uses costs of relapse unrelated to the intervention received in the adjuvant setting. Furthermore, unlike the manufacturer's submission, the Assessment Group model included differences in pharmacy costs between oxaliplatin plus 5-FU/FA and 5-FU/FA alone. Finally, by setting the model parameters to the worst-case scenario, the estimated CQG in the Assessment Group model was increased to £7587. In the absence of studies directly comparing oxaliplatin plus 5-FU/FA (de Gramont) with capecitabine, the Assessment Group modelled indirect comparisons of oxaliplatin plus 5-FU/FA (de Gramont) versus capecitabine, and oxaliplatin plus 5-FU/FA versus bolus 5-FU/FA, in the adjuvant treatment of stage III colon cancer. For the first comparison, two approaches were taken. The first used the absolute predicted long-term survival and cost data of the Assessment Group model, and the second used the marginal cost effectiveness of oxaliplatin plus 5-FU/FA (de Gramont) and of capecitabine against the comparator arms of MOSAIC and X-ACT, respectively. The estimated CQGs for oxaliplatin plus 5-FU/FA (de Gramont) compared with capecitabine were £12,874 (£16,283 additional costs and 1.26 QALYs) and £46,814 (£16,283 additional costs and 0.35 QALYs) for the first and second approach, respectively. The second comparison, using data from the MOSAIC and X-ACT trials, resulted in an estimated CQG of £5777 for oxaliplatin plus 5-FU/FA (de Gramont) versus bolus 5-FU/FA (Mayo Clinic regimen), consisting of £12,963 in additional costs and 2.24 QALYs. # Consideration of the evidence The Committee reviewed the data available on the clinical and cost effectiveness of capecitabine as monotherapy, and oxaliplatin in combination with 5-FU/FA, in the adjuvant treatment of stage III (Dukes' C) colon cancer. It considered evidence on the nature of the condition and on the value that people with colon cancer, those who represent them, and clinical experts placed on the benefits of the two drugs in the adjuvant treatment of the condition. It was also mindful of the need to take account of the effective use of NHS resources. In reviewing the evidence of clinical effectiveness for both capecitabine and oxaliplatin the Committee noted that to date, no statistically significant benefit on overall survival of these interventions over their comparators has been reported from the trial populations of X-ACT, MOSAIC and NSABP C-07. However, the Committee considered it reasonable to assume that for the purpose of the economic model, the 3-year disease-free survival benefits reported in these clinical trials would predict 5-year overall survival benefits for the adjuvant treatment of people with stage III (Dukes' C) colon cancer. The Committee considered the fact that participants in trials for adjuvant treatment of stage III colon cancer are often younger than those who would be treated in clinical practice. It heard testimony from clinical experts that it is reasonable to extrapolate these results to older patients, that appropriately selected older people show a relatively good tolerability profile to the drugs, and that the effect on overall survival in those older people in clinical practice is comparable with that seen in the younger trial participants. Additionally, the Committee heard evidence from the Assessment Group that, if an older cohort of people was used in the model that was more representative of the population under consideration, and survival benefits for this group were assumed to be equivalent to those for the group of trial participants, the cost-effectiveness estimates would not materially change. The Committee carefully considered the rates of adverse events reported for capecitabine and oxaliplatin in the three pivotal clinical trials. It particularly noted sensory neuropathy following treatment with oxaliplatin. It heard testimony from clinical experts that not only grade 3 but also grade 2 neuropathies can be severely debilitating, and continue long term in a significant percentage of patients. This is particularly problematic in adjuvant treatment. It further heard that the appearance of sensory neuropathy was not predictable, but the degree to which individuals are affected by such adverse events depends to some extent on their fitness. The Committee considered the Assessment Group's assumptions and sensitivity analyses used in its economic model and noted the following points. They expressed some concerns regarding the utility values adopted, but accepted that these were the best available from the literature and gave a plausible set of results. They were concerned that the adverse effects of the drugs, particularly oxaliplatin-induced sensory neuropathy, could have been undervalued by the Assessment Group. They noted that recurrence of a tumour more than 5 years after first receiving adjuvant treatment is possible; however, the relevant sensitivity analysis from the economic model did not affect the cost effectiveness materially. They were aware that when findings from the FOCUS and GERCOR trials (which looked at advanced colorectal cancer) are used in estimating costs of relapse, these costs are likely to be an underestimate of the real costs; however, it was accepted that imputing higher costs of relapse would lead to more favourable cost effectiveness for capecitabine and oxaliplatin plus 5-FU/FA. They considered that the use of oxaliplatin in the adjuvant treatment of colon cancer could restrict its use in advanced colorectal cancer, but that this would depend on when the relapse was experienced after first use of the drug in the adjuvant setting. They were persuaded that it was most important to achieve the benefits of adjuvant treatment early in order to avoid or delay relapse. Overall, the Committee accepted that capecitabine as monotherapy, and the combination of oxaliplatin plus 5-FU/FA, should be considered as cost-effective options for the adjuvant treatment of people with stage III (Dukes' stage C) colon cancer. The Committee was mindful of the substantial uncertainty within the indirect comparisons reported in the economic analyses by the Assessment Group. It therefore did not consider the comparison between oxaliplatin plus 5-FU/FA and capecitabine to be informative for guidance. The Committee was clear that, given the different toxicities of the drugs, particularly the risk of longer-term sensory neuropathy with oxaliplatin, the choice of therapy should be made in clear consultation with the patient, and in careful consideration of the patient's performance status.# Recommendations for further research Research is needed to compare the effectiveness, tolerability, acceptability to patients and costs of the different oxaliplatin plus 5-FU regimens in the adjuvant setting (particularly those that combine oxaliplatin with oral forms of 5-FU). The optimum duration of adjuvant therapy is not known. Shorter duration might potentially reduce the costs, inconvenience, toxicity and risks of adjuvant therapy, but large trials are required to determine whether there is any reduction in efficacy. There is a need for future cancer trial protocols of the adjuvant treatment for stage III (Dukes' C) colon cancer to incorporate more detailed resource data collection strategies and to report summary statistics that are of use within economic valuations. The degree of adherence to treatment particularly needs to be factored in. Trials should also collect data on changes in health-related QoL of participants, especially those related to adverse events. # Ongoing research (non-comprehensive list) National Surgical Adjuvant Breast and Bowel Project (NSABP-C-08). Phase III Randomized Study of Adjuvant Chemotherapy Comprising Fluorouracil, Leucovorin Calcium, and Oxaliplatin With Versus Without Bevacizumab in Patients With Resected Stage II or III Adenocarcinoma of the Colon. US. NCT00096278. National Cancer Research Institute (NCRI-QUASAR1). Phase III Randomized Study of Adjuvant Chemotherapy with L-Leucovorin and Fluorouracil versus Observation in Patients with Resected Colorectal Cancer. UK. NCT00005586. North Central Cancer Treatment Group, National Cancer Institute, Eastern Cooperative Oncology Group. Phase III Randomized Study of Oxaliplatin (OXAL) Plus 5-Fluorouracil (5-FU)/Leucovorin (CF) With or Without Cetuximab (C225) After Curative Resection for Patients with Stage III Colon Cancer. US. NCT00079274. Schmoll HJ, Tabernero J, Nowacki M et al. Safety findings from a phase III trial of capecitabine plus oxaliplatin (XELOX) versus bolus 5-FU/LV as adjuvant therapy for patients with stage III colon cancer. Abstract 3523, presented at ASCO 2005. Wein A, Lehnert T, Liersch T et al. (2004) Toxicity and safety of weekly high-dose 5-FU as 24-h infusion and folinic acid (AIO regimen) in adjuvant therapy of UICC stage III colon cancer. InTACT: A multicenter phase III trial. Journal of Clinical Oncology 22 (14S July 15 Supplement): 3586. ASCO Annual Meeting Proceedings (Post-Meeting Edition). Coppola FS, Arca R, Ferro A et al. (2002) A phase III randomized trial (COLON-OXALAD) of adjuvant therapy for very high risk colon cancer (CC) patients (pts) with oxaliplatin (OXA) and bolus 5-fluorouracil (5-FU)/folinic acid (FA): a toxicity report. ASCO Annual Meeting: 656.# Implications for the NHS Since the final appraisal determination was issued, NICE has carried out more detailed costing analysis to support implementation of the guidance. The following costing tools are available from the NICE website: A national costing report, which estimates the overall resource impact associated with implementation. A local costing template: a simple spreadsheet that can be used to estimate the local cost of implementation.# Related guidance NICE has issued the following related technology appraisal guidance. Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. Review of Technology Appraisal 33. NICE technology appraisal guidance no. 93 (2005). Guidance on the use of capecitabine and tegafur with uracil for metastatic colorectal cancer. NICE technology appraisal guidance no. 61 (2003). Guidance on the use of laparoscopic surgery for colorectal cancer. NICE technology appraisal guidance no. 17 (2000). The use of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. NICE technology appraisal guidance 118 (2007).# Review of guidance The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators. The guidance on this technology will be considered for review in June 2009. Andrew DillonChief Executive April 2006# Appendix C. Detail on criteria for audit of the use of capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer # Possible objectives for an audit An audit on the adjuvant treatment of people with stage III (Dukes' C) colon cancer could be carried out to ensure that capecitabine and oxaliplatin are being used appropriately. # Possible patients to be included in the audit An audit could be carried out on people with stage III (Dukes' C) colon cancer seen over a suitable time period for audit; for example, 6 months or a year. # Measures that could be used as a basis for an audit The measures that could be used in an audit of capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer are as follows. Criterion Standard Exception Definition of terms . A person with stage III (Dukes' C) colon cancer is offered the following as options for adjuvant treatment following surgery for the condition: a. capecitabine monotherapy and b. oxaliplatin in combination with 5-FU/FA % of people who have stage III (Dukes' C) colon cancer and to whom adjuvant treatment is offered A. The person has a contraindication to capecitabine B. The person has a contraindication to oxaliplatin, 5-FU, or folinic acid Clinicians will need to agree locally on how the offer of the treatment options is documented for audit purposes. Contraindications for capecitabine include severe leucopenia, neutropenia, thrombocytopenia, severe hepatic impairment or severe renal impairment. Contraindications for oxaliplatin include myelosuppression before the patient starts the first course of adjuvant treatment, as evidenced by a baseline neutrophil count of less than 2 x 109 per litre and/or a platelet count of less than 100 x 109 per litre, or peripheral neuropathy with functional impairment prior to the first course of adjuvant treatment. See the Summary of Product Characteristics for contraindications to 5‑FU/FA. . The individual and the clinician(s) responsible for treatment decide jointly on the choice of adjuvant treatment after an informed discussion % of people who have stage III (Dukes' C) colon cancer and to whom adjuvant treatment is offered None Clinicians will need to agree locally on how the discussion and decision are documented for audit purposes. The discussion should take into account contraindications and the side-effect profile of the agent(s), the method of administration, and the clinical condition and preferences of the individual. # Calculation of compliance Compliance (%) with each measure described in the table above is calculated as follows. Number of patients whose care is consistent with the criterion plus number of patients who meet any exception listed x 100 Number of patients to whom the measure applies Clinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.# Changes after publication March 2014: implementation section updated to clarify that capecitabine and oxaliplatin are recommended as options for treating stage III (Dukes' C) colon cancer. Additional minor maintenance update also carried out. March 2012: minor maintenance# About this guidance NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales. The recommendations from this guideline have been incorporated into a NICE Pathway. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.	{'Guidance': "The following are recommended as options for the adjuvant treatment of patients with stage III (Dukes' C) colon cancer following surgery for the condition:\n\ncapecitabine as monotherapy\n\noxaliplatin in combination with 5-fluorouracil and folinic acid.\n\nThe choice of adjuvant treatment should be made jointly by the individual and the clinicians responsible for treatment. The decision should be made after an informed discussion between the clinicians and the patient; this discussion should take into account contraindications and the side-effect profile of the agent(s) and the method of administration as well as the clinical condition and preferences of the individual.", 'Clinical need and practice': "Colon cancer is a malignant neoplasm arising from the lining (mucosa) of the large intestine (colon). Colorectal cancer (including cancers of the rectum as well as cancers of the colon) is the third most common cancer in the UK. Almost 30,000 new cases were registered in England and Wales in 2002, representing over 12% of all new cancer cases. The incidence of colorectal cancer increases with age. In people between the ages of 45 and 49 years the incidence is about 20 per 100,000. Among those aged 75 and above, the rate is over 300 per 100,000 per year for men and over 200 per 100,000 per year for women.\n\nIn the UK, about 26% of patients diagnosed with colorectal cancer are classified as having stage III (or C1, C2 according to the modified Dukes' classification – patients whose tumour has spread to lymph nodes) disease at the time of presentation. These patients have an overall 5-year survival rate of between 25% and 60%. About two thirds of tumours develop in the colon and the remainder in the rectum. After a complete surgical resection (undertaken with curative intent), patients with stage III colon cancer have a 50–60% chance of developing recurrent disease.\n\nThe 2004 NICE guidance on cancer services recommends that systemic chemotherapy should be offered to all patients who, after surgery for Dukes' stage C colon or rectal cancer, are fit enough to tolerate it; that a multidisciplinary team should ensure that adjuvant chemotherapy is scheduled to begin within 6 weeks of surgery; and that standard treatment is a 6-month course of 5-fluorouracil and folinic acid (5-FU/FA), given intravenously. 5-FU/FA can be given in regimens involving bolus doses or continuous infusions.\n\nIn clinical trials of adjuvant chemotherapy for colon cancer, the outcome of treatment is usually reported in terms of disease-free survival. This is commonly defined as the time from randomisation to either the first relapse, a second primary colon cancer, death from any cause (with no evidence of relapse), or when the patient is disease free (censoring time). In some trials, relapse-free survival is used as a secondary outcome measure and is defined in the same way as disease-free survival, but excludes death unrelated to disease progression or treatment. Overall survival is also often reported as a secondary endpoint, but has disadvantages as an indicator of effectiveness. (In recurrent or advanced disease the activity of the adjuvant therapy may be masked by differences in subsequent therapy.) Pooled data suggest that 5-FU/FA regimens will increase disease-free survival at 5 years from 42% to 58%, and overall survival from 51% to 64%, when compared with surgery alone.\n\n National Institute for Clinical Excellence (2004). Improving outcomes in colorectal cancers: manual update. Guidance on cancer services.", 'The technologies': "# Capecitabine\n\nCapecitabine (Xeloda, Roche) is an orally administered precursor of the cytotoxic moiety 5-fluorouracil (5-FU). It is licensed for the adjuvant treatment of patients following surgery of stage III (Dukes' stage C) colon cancer, and for first-line monotherapy for metastatic colorectal cancer.\n\nCapecitabine is contraindicated in patients with severe leucopenia, neutropenia or thrombocytopenia, and in patients with severe hepatic impairment or severe renal impairment. Dose-limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and hand–foot syndrome (erythema and desquamation of the palms and the soles of the feet). Most adverse events are reversible and do not require permanent discontinuation of therapy, although doses may need to be withheld or reduced. For full details of side effects and contraindications, see the Summary of Product Characteristics.\n\nThe cost of 60 x 150-mg tablets and 120 x 500-mg tablets of capecitabine is £44.47 and £295.06, respectively (excluding VAT; British National Formulary [BNF] 50). For a person with a surface area of 1.75 m2 receiving the recommended dose, the cost of treatment with capecitabine is £301.46 per cycle. Costs may vary in different settings because of negotiated procurement discounts.\n\n# Oxaliplatin\n\nOxaliplatin (Eloxatin, Sanofi-Aventis) is a water-soluble platinum-based cytotoxic drug that prevents DNA replication, and hence cell division, by cross-linking DNA. Oxaliplatin in combination with intravenous 5-FU/FA is licensed for adjuvant treatment of stage III (Dukes' C) colon cancer after complete resection of primary tumour, and for the treatment of metastatic colorectal cancer. Neurotoxic side effects can be dose limiting. Acute paraesthesias or dysaesthesias of the extremities, triggered or exacerbated by cold temperatures, occur in 85–95% of people within hours of oxaliplatin infusion. These symptoms are normally mild and resolve within hours or days. However, with increasing cumulative dose, peripheral sensory symptoms increase in duration and intensity. Symptoms may progress to functional impairment. Cumulative neurotoxicity is reversible in most, but not all, cases, with regression of symptoms occurring in 4–6 months in about 80% of patients (see also 4.1.13). Other side effects include gastrointestinal disturbances and myelosuppression.\n\nOxaliplatin is contraindicated in patients who have myelosuppression before starting the first course, as evidenced by a baseline neutrophil count of less than 2 x 109 per litre and/or a platelet count of less than 100 x 109 per litre. It is also contraindicated in patients who have a peripheral neuropathy with functional impairment before the first course. For full details of side effects and contraindications, see the Summary of Product Characteristics.\n\nThe recommended dose for oxaliplatin is 85 mg/m2 when given in combination with 5-FU/FA. It is administered as an intravenous infusion over 2–6 hours every 2 weeks (usually for 6 months) followed by an infusion of 5-FU/FA.\n\nVials containing 50 mg and 100 mg cost £165 and £330, respectively (excluding VAT; BNF 50). For a person with a surface area of 1.75 m2 receiving the recommended dose, the cost of treatment with oxaliplatin is £495 per cycle. Costs may vary in different settings because of negotiated procurement discounts.", 'Evidence and interpretation': "The Appraisal Committee (Appendix A) considered evidence from a number of sources (Appendix B).\n\n# Clinical effectiveness\n\n## Capecitabine\n\nOne randomised, open-label, active-controlled trial with 1987 participants, the Xeloda – Adjuvant Chemotherapy Trial (X-ACT), investigated the efficacy and safety of capecitabine treatment versus 5-FU/FA treatment (bolus Mayo Clinic regimen) in the postoperative adjuvant setting in patients with stage III (Dukes' C) colon cancer. Apart from the protocol-specified analyses, ad hoc analyses were carried out at the request of the US Food and Drugs Administration (FDA).\n\nFor the primary endpoint of disease-free survival, the study was powered to establish non-inferiority, defined so that the upper limit of the 95% confidence interval (CI) around the hazard ratio was no more than 1.25. The median age of participants was 62 years in the capecitabine arm and 63 years in the 5-FU/FA arm.\n\nAfter a median follow-up of 3.8 years, 35% of patients in the capecitabine arm had experienced disease recurrence (relapse or new occurrence of colon cancer) or died, compared with 39% in the 5-FU/FA arm. The hazard ratio for recurrence was 0.87 (95% CI, 0.75 to 1.00). Updated analyses, not specified in the protocol, showed that with longer follow-up (minimum 3 years and median 4.4 years) capecitabine remained at least as effective as 5-FU/FA.\n\nOverall survival data were not mature at the time of the primary (specified) and secondary (ad hoc) analyses. However, at 3.8 years median follow-up, 80% and 77% of patients were alive in the capecitabine and 5-FU/FA arms, respectively.\n\nQuality of life (QoL) was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), with global health status being the primary parameter for the QoL evaluation. In both treatment groups, scores for global health status were constant over time (from baseline to 25 weeks of trial treatment) and there were no major (statistically significant) differences between the two groups.\n\nSevere stomatitis and hair loss were significantly more common in the participants treated with 5-FU/FA. In addition, neutropenia, as a clinical adverse event requiring medical intervention, was significantly less common in participants treated with capecitabine. The only treatment-related adverse events occurring statistically significantly more frequently with capecitabine than with 5-FU/FA were hand–foot syndrome (p < 0.001) and hyperbilirubinaemia.\n\nA submission by a professional organisation reports that 'when given a choice, most cancer patients prefer oral instead of intravenous therapy, but only if the treatment is equally effective; patients cite increased convenience, less distress over repeated intravenous access and more control over their own treatment as major factors'.\n\n## Oxaliplatin\n\nTwo phase III, randomised active-controlled trials that compared oxaliplatin with standard treatment were identified by the Assessment Group. The first was the Multicenter International Study of Oxaliplatin/5-fluorouracil and leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) trial. (This was open-label and had 2246 participants – 60% with stage III and the remainder with stage II colon cancer.) The second trial was the National Surgical Adjuvant Breast and Bowel Project (NSABP C-07) trial. (This had 2492 participants – 71% with stage III and the remainder with stage II colon cancer.) The NSABP C-07 trial was only available in abstract form.\n\nIn the MOSAIC trial, oxaliplatin was combined with 5-FU/FA in the de Gramont regimen (an infusional regimen) and compared with 5-FU/FA alone (also given in the de Gramont regimen). In the NSABP C-07 trial, standard treatment consisted of 5-FU/FA administered via a bolus regimen (Roswell Park) and this was subsequently compared with oxaliplatin in combination with the same bolus regimen. In addition to the protocol-specified analyses, ad hoc analyses were carried out at the request of the FDA in the MOSAIC trial. The median age of trial participants was 61 years and 60 years in the oxaliplatin plus 5-FU/FA and the 5-FU/FA alone groups, respectively. NSABP C-07 did not report age at baseline. QoL data were not routinely collected within either trial.\n\nIn both trials the addition of oxaliplatin to 5-FU/FA, albeit administered via different regimens, led to a statistically significant reduction in rate of relapse when compared with 5-FU/FA monotherapy. Analysis of disease-free survival at 3 years showed a hazard ratio for recurrence of 0.77 (95% CI, 0.65 to 0.91) in the MOSAIC trial (median follow-up 37.9 months; intention to treat analysis), and 0.79 (95% CI, 0.67 to 0.93) in the NSABP C-07 trial (median follow-up 34 months, according to protocol analysis). Additional analyses on MOSAIC – requested by regulatory authorities – showed a 24% reduction in the rate of relapse (improved disease-free survival) at a median follow-up of 4 years (hazard ratio for recurrence 0.76; 95% CI, 0.65 to 0.90).\n\nOverall survival results for MOSAIC and NSABP C-07 are to be calculated at follow-up periods of 6 years and 5 years respectively. No mature data are available for MOSAIC at present, and the interim 3-year and 4-year analyses report no statistically significant differences in overall survival between the study groups; 88.2% and 87.0% still alive at 38 months in the oxaliplatin plus 5-FU/FA and the 5-FU/FA arms, respectively, and a hazard ratio for death of 0.89 (95% CI, 0.72 to 1.09) in the 4-year analysis favouring the addition of oxaliplatin. The abstract of the NSABP C-07 trial did not report overall survival.\n\nOnly in the MOSAIC study were subgroups prespecified according to stage of the disease, with results reported separately. For participants with stage III colon cancer, the hazard ratio for recurrence was found to be 0.76 (95% CI, 0.62 to 0.92) at 3 years, and 0.75 (95% CI, 0.62 to 0.90) at 4 years. The percentages of people experiencing relapse or death in the oxaliplatin plus 5-FU/FA and the 5-FU/FA arms were 26.9% and 33.5%, respectively. The hazard ratio for death for stage III patients in MOSAIC was 0.86 (95% CI, 0.66 to 1.11) at 3 years. Although the MOSAIC study was adequately powered to demonstrate improved survival outcomes in patients with stage II (40% of total population) or III (60% of total population) disease, the study was not powered to detect a therapeutic effect by subgroup.\n\nIn the MOSAIC trial more participants discontinued treatment because of adverse events in the oxaliplatin plus 5-FU/FA group (14.4%) than in the group receiving 5-FU/FA monotherapy (5.6%). Neutropenia and paraesthesia are the toxicities most reported for oxaliplatin plus 5-FU/FA. Grade 3 peripheral neuropathy was observed in 12.4% of patients during treatment (median number of cycles 12; equivalent to about 6 months of chemotherapy), and in 1.1% and 0.5% of patients at 12 months and 18 months follow-up, respectively. Other frequent adverse events in the oxaliplatin plus infusional 5-FU/FA group were diarrhoea, nausea and vomiting.\n\nGrade 3 neurotoxicity was observed in 8% of patients receiving oxaliplatin plus bolus 5-FU/FA in the NSABP C-07 trial compared with 1% of patients receiving 5-FU/FA alone. After 1 year of follow-up, grade 3 neuropathy in the oxaliplatin plus 5-FU/FA group remained in 0.5% of patients. The Assessment Group noted that the incidence of grade 3/4 diarrhoea in the combination arm was much higher than that observed in MOSAIC: approximately 40% and 11%, respectively.\n\nA joint submission by professional organisations reports that oxaliplatin causes a unique cold-related peripheral neuropathy affecting over 90% of patients during treatment, and that symptoms are still present to a greater or lesser degree 18 months after completing treatment in 24% of patients.\n\nAnother submission by a professional group refers to the combined incidence of grade 2 and 3 neurosensory symptoms as reported in the MOSAIC trial. It notes that 18 months after completion of treatment, 3.9% of patients had persistent debilitating symptoms.\n\n## Comparison of infusional and bolus regimes for 5-FU/FA\n\nThree randomised comparisons of bolus versus infusional regimens have been published. Only two studies followed individuals for 5 years – a suitable proxy for long-term survival. The evidence reviewed suggests that infusional intravenous 5-FU-based adjuvant therapy is equivalent to, but has relatively less toxicity than, traditional bolus 5-FU/FA in extending survival and QoL. However, there are concerns about catheter-associated complications, patient inconvenience and the cost of infusional treatment. In the adjuvant setting, the weekly intravenous bolus 5-FU/FA for 30 weeks (QUASAR regimen) is most commonly used in the NHS in England and Wales. However, there remains significant geographical variation in the 5-FU-based regimens currently in use in the UK.\n\n# Cost effectiveness\n\nThe Assessment Group reviewed three published economic evaluations, two of which were submitted by manufacturers. It also presented its own three-state Markov model to estimate the cost effectiveness of oxaliplatin plus 5-FU/FA versus 5-FU/FA alone, and of capecitabine versus 5-FU/FA alone.\n\nIn the Assessment Group model, hypothetical individuals were assumed to move between three states: alive without relapse, alive with relapse, and dead. Transition probabilities in the Assessment Group model and one of the manufacturer models were estimated from the disease-free survival curve and the partitioned overall survival curves for patients with and without relapse. This joint modelling of disease-free and overall survival differs from the approach adopted in the model submitted by the manufacturer of capecitabine, where there was independent modelling of relapse-free survival and overall survival with inconsistent results.\n\nKey assumptions used in the Assessment Group model were as follows.\n\nOverall survival of people who relapse is assumed to be independent of the time of relapse.\n\nOverall survival of people who relapse is equivalent to that of patients who are initially diagnosed with advanced (stage IV – Dukes' D) colorectal cancer.\n\nAll relapses occur within the 5 years following resection of the primary tumour.\n\nOverall survival of people alive and disease free at 5 years is similar to the survival in the general population, adjusting for age and sex.\n\nPeople who relapse are assumed to receive first-line 5-FU/FA followed upon progression by single-agent irinotecan.\n\nPeople receiving 5-FU/FA via the de Gramont regimen are assumed to receive their treatment on an outpatient basis. All of these assumptions, except for the last two, are also used in the model submitted by the manufacturer of oxaliplatin. Instead of using the cost of a specific chemotherapy regimen to estimate cost of relapse, the manufacturer's model uses an average cost of relapse that is calculated from a distribution using costs of treatment for four different types of relapse.\n\nEvidence for estimating preference-based utilities for the different health states is scarce. The submissions from the manufacturers of both drugs based their utility estimates on a study of 173 patients with colorectal cancer (40 of whom had stage III disease). In this study, generic and cancer-specific QoL tools were administered at regular intervals following diagnosis, starting at 13 months post diagnosis. Although the study did not differentiate between patients who relapsed and those who did not, both submissions used a disutility of approximately 0.2 for people who experienced relapse. In the manufacturer submission for oxaliplatin, utilities while on treatment were also corrected for adverse events.\n\nThe Assessment Group noted that because the study used in the manufacturers' submissions started long after diagnosis, and a relatively small proportion of patients had stage III disease, they could only use data from this study to estimate the utility for people in remission (0.92).\n\nFrom a second study that elicited utilities from 81 patients with colorectal cancer with all stages of the disease (including those with stage III undergoing resection and chemotherapy), utilities were taken for those people undergoing treatment without adverse events (0.7) and with adverse events (0.63), as well as for those who relapse (0.24).\n\n## Capecitabine\n\nThe key cost driver of the economic analysis submitted by the manufacturer was the difference in the drug acquisition and administration costs between the capecitabine and 5-FU/FA (Mayo Clinic regimen) arms. Acquisition costs were approximately £1400 higher for the capecitabine arm, whereas administration costs and costs associated with adverse events were lower for the capecitabine arm – approximately £4750 and £300 per patient for 5-FU/FA and capecitabine, respectively.\n\nPrimarily because of reduced drug administration costs associated with capecitabine (long-term costs were assumed to be approximately equal), the manufacturer's submission concluded that capecitabine is cost saving compared with 5-FU/FA, costing on average £3653 less per patient. Combined with lifetime extrapolated relapse-free and overall survival benefits, treatment with capecitabine also leads to a gain of 0.75 quality-adjusted life years (QALYs) in the manufacturer's model. The one-way sensitivity analyses and extreme analysis showed that the only significant uncertain driver for varying cost effectiveness is the cost per administration visit. Scenario analyses on the regimen used for 5-FU/FA indicate that capecitabine remains cost saving whichever regimen is used.\n\nIn the Assessment Group model, total cost savings from the use of capecitabine compared with the Mayo Clinic 5-FU/FA regimen are slightly less than those reported in the manufacturer's submission (£3320). This is primarily due to the differences between the two models in the costs associated with relapse and a difference in pharmacy costs between capecitabine and 5-FU/FA that was included in the Assessment Group model but not in the manufacturer's submission. The higher QALY gain associated with capecitabine in the Assessment Group model (0.98 QALYs) appears to be attributable to the different methods used to estimate survival. In all the one-way sensitivity analyses, capecitabine treatment results in a cost saving when compared with 5-FU/FA in the Mayo Clinic regimen.\n\n## Oxaliplatin\n\nTwo published economic analyses that considered oxaliplatin plus 5-FU/FA in the adjuvant setting were included in the Assessment Report. One of these analyses was conducted from a non-UK perspective and used survival estimates from trials of oxaliplatin plus 5-FU/FA in advanced colorectal cancer that are unlikely to be representative of survival outcomes for patients receiving adjuvant chemotherapy. Further analysis by the Assessment Group of the marginal cost and survival results given in the paper suggested that the cost per life year gained of the addition of oxaliplatin to 5-FU/FA is £24,952. An abstract of another economic analysis was presented at the 2005 meeting of the American Society of Clinical Oncology (ASCO) and updated to form the basis of the manufacturer's submission to the appraisal (see 4.2.11 below). The cost per life year gained associated with oxaliplatin plus infusional 5-FU/FA in this study was estimated to be US$27,300.\n\nThe economic model submitted by the manufacturer was based on patient-level data from the MOSAIC trial. It used observed mortality and disease-free survival, as well as the relationship between disease-free survival and overall survival, to estimate the difference in overall survival between the two treatment arms. Data from MOSAIC that relate to the cohort of patients with stage III colon cancer were used to report a base-case cost per QALY gained (CQG) of £4805 for oxaliplatin plus infusional 5-FU/FA versus infusional 5-FU/FA alone, calculated over a 50-year time horizon. This CQG estimate consists of a difference in costs of £3267 and a difference in benefits of 0.68 QALYs. When a one-way sensitivity analysis was performed, and benefits and costs were limited to those within trial data, the CQG increased to £56,780. There was no other one-way sensitivity analysis that resulted in a very different estimate from that of the base case – not even a doubling of the disutility for relapse (to 0.4). The manufacturer suggests that the difference between its base-case results (for stage II and III combined – CQG of £7210) and those of the published economic analyses is probably due to the lower drug acquisition costs of oxaliplatin in the UK compared with the US.\n\nIn an addendum to its submission the manufacturer presented a second cost-effectiveness analysis, now based on the NSABP C-07 trial. Equivalent efficacy (0.68 QALYs gained) was assumed for oxaliplatin plus bolus 5-FU/FA (Mayo Clinic regimen) and oxaliplatin plus 5-FU/FA (de Gramont). When combined with a cost difference of £4246 between oxaliplatin plus bolus 5-FU/FA (Mayo Clinic regimen) and 5-FU/FA alone (Mayo Clinic regimen), this analysis resulted in a CQG estimate of £6244 for oxaliplatin plus 5-FU/FA relative to 5-FU/FA alone.\n\nIncremental benefits in the Assessment Group model were greater than those in the manufacturer's submission (1.33 versus 0.68 QALYs) when oxaliplatin plus 5-FU/FA (de Gramont) was compared with 5-FU/FA alone (de Gramont). Reasons for this lie in the differences in methods used for long-term extrapolation of survival curves and utility estimates used for those people that relapse in the economic model. When incremental benefits were combined with a cost difference that was also greater than that in the manufacturer's submission (£3940), the Assessment Group model resulted in an estimated CQG of £2970. This cost difference arises because the manufacturer's model uses differential costs of relapse for the 5-FU/FA and combination arms, whereas the Assessment Group model uses costs of relapse unrelated to the intervention received in the adjuvant setting. Furthermore, unlike the manufacturer's submission, the Assessment Group model included differences in pharmacy costs between oxaliplatin plus 5-FU/FA and 5-FU/FA alone. Finally, by setting the model parameters to the worst-case scenario, the estimated CQG in the Assessment Group model was increased to £7587.\n\nIn the absence of studies directly comparing oxaliplatin plus 5-FU/FA (de Gramont) with capecitabine, the Assessment Group modelled indirect comparisons of oxaliplatin plus 5-FU/FA (de Gramont) versus capecitabine, and oxaliplatin plus 5-FU/FA versus bolus 5-FU/FA, in the adjuvant treatment of stage III colon cancer.\n\nFor the first comparison, two approaches were taken. The first used the absolute predicted long-term survival and cost data of the Assessment Group model, and the second used the marginal cost effectiveness of oxaliplatin plus 5-FU/FA (de Gramont) and of capecitabine against the comparator arms of MOSAIC and X-ACT, respectively. The estimated CQGs for oxaliplatin plus 5-FU/FA (de Gramont) compared with capecitabine were £12,874 (£16,283 additional costs and 1.26 QALYs) and £46,814 (£16,283 additional costs and 0.35 QALYs) for the first and second approach, respectively.\n\nThe second comparison, using data from the MOSAIC and X-ACT trials, resulted in an estimated CQG of £5777 for oxaliplatin plus 5-FU/FA (de Gramont) versus bolus 5-FU/FA (Mayo Clinic regimen), consisting of £12,963 in additional costs and 2.24 QALYs.\n\n# Consideration of the evidence\n\nThe Committee reviewed the data available on the clinical and cost effectiveness of capecitabine as monotherapy, and oxaliplatin in combination with 5-FU/FA, in the adjuvant treatment of stage III (Dukes' C) colon cancer. It considered evidence on the nature of the condition and on the value that people with colon cancer, those who represent them, and clinical experts placed on the benefits of the two drugs in the adjuvant treatment of the condition. It was also mindful of the need to take account of the effective use of NHS resources.\n\nIn reviewing the evidence of clinical effectiveness for both capecitabine and oxaliplatin the Committee noted that to date, no statistically significant benefit on overall survival of these interventions over their comparators has been reported from the trial populations of X-ACT, MOSAIC and NSABP C-07. However, the Committee considered it reasonable to assume that for the purpose of the economic model, the 3-year disease-free survival benefits reported in these clinical trials would predict 5-year overall survival benefits for the adjuvant treatment of people with stage III (Dukes' C) colon cancer.\n\nThe Committee considered the fact that participants in trials for adjuvant treatment of stage III colon cancer are often younger than those who would be treated in clinical practice. It heard testimony from clinical experts that it is reasonable to extrapolate these results to older patients, that appropriately selected older people show a relatively good tolerability profile to the drugs, and that the effect on overall survival in those older people in clinical practice is comparable with that seen in the younger trial participants. Additionally, the Committee heard evidence from the Assessment Group that, if an older cohort of people was used in the model that was more representative of the population under consideration, and survival benefits for this group were assumed to be equivalent to those for the group of trial participants, the cost-effectiveness estimates would not materially change.\n\nThe Committee carefully considered the rates of adverse events reported for capecitabine and oxaliplatin in the three pivotal clinical trials. It particularly noted sensory neuropathy following treatment with oxaliplatin. It heard testimony from clinical experts that not only grade 3 but also grade 2 neuropathies can be severely debilitating, and continue long term in a significant percentage of patients. This is particularly problematic in adjuvant treatment. It further heard that the appearance of sensory neuropathy was not predictable, but the degree to which individuals are affected by such adverse events depends to some extent on their fitness.\n\nThe Committee considered the Assessment Group's assumptions and sensitivity analyses used in its economic model and noted the following points.\n\nThey expressed some concerns regarding the utility values adopted, but accepted that these were the best available from the literature and gave a plausible set of results.\n\nThey were concerned that the adverse effects of the drugs, particularly oxaliplatin-induced sensory neuropathy, could have been undervalued by the Assessment Group.\n\nThey noted that recurrence of a tumour more than 5 years after first receiving adjuvant treatment is possible; however, the relevant sensitivity analysis from the economic model did not affect the cost effectiveness materially.\n\nThey were aware that when findings from the FOCUS and GERCOR trials (which looked at advanced colorectal cancer) are used in estimating costs of relapse, these costs are likely to be an underestimate of the real costs; however, it was accepted that imputing higher costs of relapse would lead to more favourable cost effectiveness for capecitabine and oxaliplatin plus 5-FU/FA.\n\nThey considered that the use of oxaliplatin in the adjuvant treatment of colon cancer could restrict its use in advanced colorectal cancer, but that this would depend on when the relapse was experienced after first use of the drug in the adjuvant setting. They were persuaded that it was most important to achieve the benefits of adjuvant treatment early in order to avoid or delay relapse.\n\nOverall, the Committee accepted that capecitabine as monotherapy, and the combination of oxaliplatin plus 5-FU/FA, should be considered as cost-effective options for the adjuvant treatment of people with stage III (Dukes' stage C) colon cancer.\n\nThe Committee was mindful of the substantial uncertainty within the indirect comparisons reported in the economic analyses by the Assessment Group. It therefore did not consider the comparison between oxaliplatin plus 5-FU/FA and capecitabine to be informative for guidance.\n\nThe Committee was clear that, given the different toxicities of the drugs, particularly the risk of longer-term sensory neuropathy with oxaliplatin, the choice of therapy should be made in clear consultation with the patient, and in careful consideration of the patient's performance status.", 'Recommendations for further research': "Research is needed to compare the effectiveness, tolerability, acceptability to patients and costs of the different oxaliplatin plus 5-FU regimens in the adjuvant setting (particularly those that combine oxaliplatin with oral forms of 5-FU).\n\nThe optimum duration of adjuvant therapy is not known. Shorter duration might potentially reduce the costs, inconvenience, toxicity and risks of adjuvant therapy, but large trials are required to determine whether there is any reduction in efficacy.\n\nThere is a need for future cancer trial protocols of the adjuvant treatment for stage III (Dukes' C) colon cancer to incorporate more detailed resource data collection strategies and to report summary statistics that are of use within economic valuations. The degree of adherence to treatment particularly needs to be factored in. Trials should also collect data on changes in health-related QoL of participants, especially those related to adverse events.\n\n# Ongoing research (non-comprehensive list)\n\nNational Surgical Adjuvant Breast and Bowel Project (NSABP-C-08). Phase III Randomized Study of Adjuvant Chemotherapy Comprising Fluorouracil, Leucovorin Calcium, and Oxaliplatin With Versus Without Bevacizumab in Patients With Resected Stage II or III Adenocarcinoma of the Colon. US. NCT00096278.\n\nNational Cancer Research Institute (NCRI-QUASAR1). Phase III Randomized Study of Adjuvant Chemotherapy with L-Leucovorin and Fluorouracil versus Observation in Patients with Resected Colorectal Cancer. UK. NCT00005586.\n\nNorth Central Cancer Treatment Group, National Cancer Institute, Eastern Cooperative Oncology Group. Phase III Randomized Study of Oxaliplatin (OXAL) Plus 5-Fluorouracil (5-FU)/Leucovorin (CF) With or Without Cetuximab (C225) After Curative Resection for Patients with Stage III Colon Cancer. US. NCT00079274.\n\nSchmoll HJ, Tabernero J, Nowacki M et al. Safety findings from a phase III trial of capecitabine plus oxaliplatin (XELOX) versus bolus 5-FU/LV as adjuvant therapy for patients with stage III colon cancer. Abstract 3523, presented at ASCO 2005.\n\nWein A, Lehnert T, Liersch T et al. (2004) Toxicity and safety of weekly high-dose 5-FU as 24-h infusion and folinic acid (AIO regimen) in adjuvant therapy of UICC stage III colon cancer. InTACT: A multicenter phase III trial. Journal of Clinical Oncology 22 (14S July 15 Supplement): 3586. ASCO Annual Meeting Proceedings (Post-Meeting Edition).\n\nCoppola FS, Arca R, Ferro A et al. (2002) A phase III randomized trial (COLON-OXALAD) of adjuvant therapy for very high risk colon cancer (CC) patients (pts) with oxaliplatin (OXA) and bolus 5-fluorouracil (5-FU)/folinic acid (FA): a toxicity report. ASCO Annual Meeting: 656.", 'Implications for the NHS': 'Since the final appraisal determination was issued, NICE has carried out more detailed costing analysis to support implementation of the guidance. The following costing tools are available from the NICE website:\n\nA national costing report, which estimates the overall resource impact associated with implementation.\n\nA local costing template: a simple spreadsheet that can be used to estimate the local cost of implementation.', 'Related guidance': 'NICE has issued the following related technology appraisal guidance.\n\nIrinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. Review of Technology Appraisal 33. NICE technology appraisal guidance no. 93 (2005).[Replaced by NICE clinical guideline 131]\n\nGuidance on the use of capecitabine and tegafur with uracil for metastatic colorectal cancer.\n NICE technology appraisal guidance no. 61 (2003).\n\nGuidance on the use of laparoscopic surgery for colorectal cancer. NICE technology appraisal guidance no. 17 (2000).[Replaced by NICE technology appraisal guidance 105]\n\nThe use of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. NICE technology appraisal guidance 118 (2007).', 'Review of guidance': 'The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators.\n\nThe guidance on this technology will be considered for review in June 2009.\n\nAndrew DillonChief Executive April 2006', "Appendix C. Detail on criteria for audit of the use of capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer": "# Possible objectives for an audit\n\nAn audit on the adjuvant treatment of people with stage III (Dukes' C) colon cancer could be carried out to ensure that capecitabine and oxaliplatin are being used appropriately.\n\n# Possible patients to be included in the audit\n\nAn audit could be carried out on people with stage III (Dukes' C) colon cancer seen over a suitable time period for audit; for example, 6 months or a year.\n\n# Measures that could be used as a basis for an audit\n\nThe measures that could be used in an audit of capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer are as follows.\n\nCriterion\n\nStandard\n\nException\n\nDefinition of terms\n\n. A person with stage III (Dukes' C) colon cancer is offered the following as options for adjuvant treatment following surgery for the condition:\n\na. capecitabine monotherapy and\n\nb. oxaliplatin in combination with 5-FU/FA\n\n% of people who have stage III (Dukes' C) colon cancer and to whom adjuvant treatment is offered\n\nA. The person has a contraindication to capecitabine\n\nB. The person has a contraindication to oxaliplatin, 5-FU, or folinic acid\n\n\n\nClinicians will need to agree locally on how the offer of the treatment options is documented for audit purposes.\n\nContraindications for capecitabine include severe leucopenia, neutropenia, thrombocytopenia, severe hepatic impairment or severe renal impairment.\n\n\n\nContraindications for oxaliplatin include myelosuppression before the patient starts the first course of adjuvant treatment, as evidenced by a baseline neutrophil count of less than 2\xa0x\xa0109 per litre and/or a platelet count of less than 100\xa0x\xa0109 per litre, or peripheral neuropathy with functional impairment prior to the first course of adjuvant treatment.\n\n\n\nSee the Summary of Product Characteristics for contraindications to 5‑FU/FA.\n\n. The individual and the clinician(s) responsible for treatment decide jointly on the choice of adjuvant treatment after an informed discussion\n\n% of people who have stage III (Dukes' C) colon cancer and to whom adjuvant treatment is offered\n\nNone\n\nClinicians will need to agree locally on how the discussion and decision are documented for audit purposes. The discussion should take into account contraindications and the side-effect profile of the agent(s), the method of administration, and the clinical condition and preferences of the individual.\n\n# Calculation of compliance\n\nCompliance (%) with each measure described in the table above is calculated as follows.\n\nNumber of patients whose care is consistent with the criterion plus number of patients who meet any exception listed\n\n\n\nx 100\n\nNumber of patients to whom the measure applies\n\nClinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.", 'Changes after publication': "March 2014: implementation section updated to clarify that capecitabine and oxaliplatin are recommended as options for treating stage III (Dukes' C) colon cancer. Additional minor maintenance update also carried out.\n\nMarch 2012: minor maintenance", 'About this guidance': 'NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales.\n\nThe recommendations from this guideline have been incorporated into a NICE Pathway. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.'}	https://www.nice.org.uk/guidance/ta100	Evidence-based recommendations on capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer in adults.
7c65c94ffb7478e058958006ac39b5539279065e	nice	Balloon kyphoplasty for vertebral compression fractures	Balloon kyphoplasty for vertebral compression fractures # Guidance This guidance replaces previous guidance on balloon kyphoplasty for vertebral compression fractures (November 2003). Current evidence on the safety and efficacy of balloon kyphoplasty for vertebral compression fractures appears adequate to support the use of this procedure provided that normal arrangements are in place for consent, audit and clinical governance. The following are recommended. This procedure should only be undertaken with prior discussion by a specialist multidisciplinary team that includes a radiologist and a spinal surgeon, and when there are facilities for good imaging, and arrangements for good access to a spinal surgery service. Clinicians should receive training to reach an appropriate level of expertise before carrying out this procedure. In particular, they must follow the manufacturer's instructions for making the cement, to reduce the risk of embolisation.# The procedure # Indications Vertebral compression fractures are one of the most common types of osteoporotic fracture. Osteoporotic fractures are common in the elderly and particularly in postmenopausal women, but they can also be associated with other factors such as chronic steroid usage. Other causes of vertebral compression fracture include malignancy in the vertebrae or, more rarely, haemangioma. Pain is the most common symptom in patients with vertebral compression fractures. Fractures can also cause progressive spinal deformity with abnormal curvature (kyphosis). This can lead to increased risk of further fracture at adjacent levels and progressive malalignment, deformity and pain. There is also an increased risk of falls. Conventional treatment for vertebral compression fractures is focused on the alleviation of symptoms with analgesic medication and spinal support. The majority of patients become symptom free through these measures and surgery is rarely indicated. Surgery may be considered in patients whose condition is refractory to medical therapy and in whom there is continued vertebral collapse and severe pain. Recently there has been increased interest in minimally invasive procedures, including balloon kyphoplasty and vertebroplasty. # Outline of the procedure Balloon kyphoplasty is performed under local or general anaesthesia assisted by fluoroscopy. One or more levels of the spine can be treated in one session. The fractured vertebra is accessed through a small incision in the patient's back. A hand drill is used to create a channel through which one or two balloon-like devices (inflatable bone tamps) can be inserted into the medullary space. The inflatable tamp is positioned in the vertebral body and filled with a radiopaque contrast medium for visualisation. The balloon is slowly inflated until the normal height of the vertebral body is restored or the balloon reaches its maximum volume. The balloon is then deflated and the cavity created filled with cement (typically polymethylmethacrylate, PMMA) at a low pressure. # Efficacy Three non-randomised studies were reviewed: two compared balloon kyphoplasty with conventional medical care (physical and analgesic therapy) and one compared the procedure with vertebroplasty. All three studies found that patients who had undergone balloon kyphoplasty had improved pain scores compared with the control group at a maximum follow-up of 24 months. In two non-randomised controlled studies, physical function following balloon kyphoplasty, as measured by the European Vertebral Osteoporosis Study Group questionnaire or Oswestry Disability Index (ODI), was shown to be significantly improved from baseline at 12 months. However, in one of these trials physical function (ODI) at 2 years was not found to be significantly different from preoperative values in either the balloon kyphoplasty group (61% vs 56%) or the vertebroplasty group (61% vs 52%). In a study of 222 patients (360 procedures), a greater than 20% restoration of lost vertebral height was achieved in 63% and 69% of fractures at the anterior and midline, respectively, and the kyphosis angle decreased from 22° to 15°. In a study comparing balloon kyphoplasty with conventional medical care, midline vertebral body height was significantly increased in the balloon kyphoplasty group compared with that at baseline and at 12 months was significantly greater than in the controls (67% vs 56%). For more details, refer to the Sources of evidence. The Specialist Advisors expressed uncertainties about whether the improvements following balloon kyphoplasty (reduced pain and height restoration) are maintained in the long term. # Safety The most commonly reported complications following balloon kyphoplasty were cement leaks and new fractures. One study of 360 procedures in 222 patients reported 38 cement leaks (11% of procedures), with one resulting in an episode of radiculopathy (the patient recovered with selective nerve block and rehabilitation). In another study of 192 procedures in 102 patients, cement leaks were reported from eight vertebral bodies (7%), all of which were asymptomatic. In one study of 115 osteoporotic patients (225 procedures), 26 patients (23%) developed a post-procedure fracture. In the non-randomised controlled study comparing balloon kyphoplasty to standard medical care, seven new fractures were observed in 7/40 (18%) patients in the balloon kyphoplasty group, compared with 11 fractures in 10/20 (50%) patients in the control group. In another non-randomised controlled study (28 patients undergoing balloon kyphoplasty, 35 fractures), six fractures to adjacent vertebrae were observed within 4 months from the procedure. Other reported adverse events during or after balloon kyphoplasty included balloon rupture (two cases), motor deficits caused by faulty puncture (one case) and epidural bleeding (one case). In a review of complications reported to the US Food and Drug Administration (Center for Devices and Radiological Health), there were 33 major complications in patients (denominator estimated at between 40,000 and 60,000 procedures) following balloon kyphoplasty. These included one death; five cases of permanent paralysis, radiculopathy, paraesthesia or loss of motor function; and 13 cases of canal intrusion or cord compression. For more details, refer to the Sources of evidence. The Specialist Advisors listed cement leakage as the most common complication following balloon kyphoplasty. They also listed infection, allergy and spinal cord or nerve root injury caused by incorrect needle placement as potential complications. # Other comments The Medicines and Healthcare products Regulatory Agency has issued a safety notice on injectable polymeric cements used in percutaneous vertebroplasty, balloon kyphoplasty and pedicle screw augmentation.# Further information NICE has issued guidance on percutaneous vertebroplasty. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in NICE's interventional procedure overview of balloon kyphoplasty for vertebral compression fractures. # Information for patients NICE has produced information for patients and carers on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Other NICE recommendations on balloon kyphoplasty Further recommendations have been made as part of the NICE guideline on metastatic spinal cord compression published in November 2008, as follows: Vertebroplasty or kyphoplasty should be considered for patients who have vertebral metastases and no evidence of MSCC or spinal instability if they have either: mechanical pain resistant to analgesia, or vertebral body collapse. Vertebroplasty or kyphoplasty for spinal metastases should only be performed after agreement between appropriate specialists including an oncologist, interventional radiologist, and spinal surgeon, and in facilities where there is good access to spinal surgery. Clinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information can be found in the NICE guideline on metastatic spinal cord compression in adults. The intervention procedure guidance on balloon kyphoplasty for vertebral compression fractures remains current, and should be read in conjunction with the clinical guideline.	{'Guidance': "This guidance replaces previous guidance on balloon kyphoplasty for vertebral compression fractures (November 2003).\n\nCurrent evidence on the safety and efficacy of balloon kyphoplasty for vertebral compression fractures appears adequate to support the use of this procedure provided that normal arrangements are in place for consent, audit and clinical governance.\n\nThe following are recommended.\n\nThis procedure should only be undertaken with prior discussion by a specialist multidisciplinary team that includes a radiologist and a spinal surgeon, and when there are facilities for good imaging, and arrangements for good access to a spinal surgery service.\n\nClinicians should receive training to reach an appropriate level of expertise before carrying out this procedure. In particular, they must follow the manufacturer's instructions for making the cement, to reduce the risk of embolisation.", 'The procedure': "# Indications\n\nVertebral compression fractures are one of the most common types of osteoporotic fracture. Osteoporotic fractures are common in the elderly and particularly in postmenopausal women, but they can also be associated with other factors such as chronic steroid usage. Other causes of vertebral compression fracture include malignancy in the vertebrae or, more rarely, haemangioma.\n\nPain is the most common symptom in patients with vertebral compression fractures. Fractures can also cause progressive spinal deformity with abnormal curvature (kyphosis). This can lead to increased risk of further fracture at adjacent levels and progressive malalignment, deformity and pain. There is also an increased risk of falls.\n\nConventional treatment for vertebral compression fractures is focused on the alleviation of symptoms with analgesic medication and spinal support. The majority of patients become symptom free through these measures and surgery is rarely indicated.\n\nSurgery may be considered in patients whose condition is refractory to medical therapy and in whom there is continued vertebral collapse and severe pain. Recently there has been increased interest in minimally invasive procedures, including balloon kyphoplasty and vertebroplasty.\n\n# Outline of the procedure\n\nBalloon kyphoplasty is performed under local or general anaesthesia assisted by fluoroscopy. One or more levels of the spine can be treated in one session.\n\nThe fractured vertebra is accessed through a small incision in the patient's back. A hand drill is used to create a channel through which one or two balloon-like devices (inflatable bone tamps) can be inserted into the medullary space. The inflatable tamp is positioned in the vertebral body and filled with a radiopaque contrast medium for visualisation. The balloon is slowly inflated until the normal height of the vertebral body is restored or the balloon reaches its maximum volume. The balloon is then deflated and the cavity created filled with cement (typically polymethylmethacrylate, PMMA) at a low pressure.\n\n# Efficacy\n\nThree non-randomised studies were reviewed: two compared balloon kyphoplasty with conventional medical care (physical and analgesic therapy) and one compared the procedure with vertebroplasty. All three studies found that patients who had undergone balloon kyphoplasty had improved pain scores compared with the control group at a maximum follow-up of 24 months.\n\nIn two non-randomised controlled studies, physical function following balloon kyphoplasty, as measured by the European Vertebral Osteoporosis Study Group questionnaire or Oswestry Disability Index (ODI), was shown to be significantly improved from baseline at 12 months. However, in one of these trials physical function (ODI) at 2 years was not found to be significantly different from preoperative values in either the balloon kyphoplasty group (61% vs 56%) or the vertebroplasty group (61% vs 52%).\n\nIn a study of 222 patients (360 procedures), a greater than 20% restoration of lost vertebral height was achieved in 63% and 69% of fractures at the anterior and midline, respectively, and the kyphosis angle decreased from 22° to 15°. In a study comparing balloon kyphoplasty with conventional medical care, midline vertebral body height was significantly increased in the balloon kyphoplasty group compared with that at baseline and at 12 months was significantly greater than in the controls (67% vs 56%). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors expressed uncertainties about whether the improvements following balloon kyphoplasty (reduced pain and height restoration) are maintained in the long term.\n\n# Safety\n\nThe most commonly reported complications following balloon kyphoplasty were cement leaks and new fractures. One study of 360 procedures in 222 patients reported 38 cement leaks (11% of procedures), with one resulting in an episode of radiculopathy (the patient recovered with selective nerve block and rehabilitation). In another study of 192 procedures in 102 patients, cement leaks were reported from eight vertebral bodies (7%), all of which were asymptomatic.\n\nIn one study of 115 osteoporotic patients (225 procedures), 26 patients (23%) developed a post-procedure fracture. In the non-randomised controlled study comparing balloon kyphoplasty to standard medical care, seven new fractures were observed in 7/40 (18%) patients in the balloon kyphoplasty group, compared with 11 fractures in 10/20 (50%) patients in the control group. In another non-randomised controlled study (28 patients undergoing balloon kyphoplasty, 35 fractures), six fractures to adjacent vertebrae were observed within 4 months from the procedure.\n\nOther reported adverse events during or after balloon kyphoplasty included balloon rupture (two cases), motor deficits caused by faulty puncture (one case) and epidural bleeding (one case).\n\nIn a review of complications reported to the US Food and Drug Administration (Center for Devices and Radiological Health), there were 33 major complications in patients (denominator estimated at between 40,000 and 60,000 procedures) following balloon kyphoplasty. These included one death; five cases of permanent paralysis, radiculopathy, paraesthesia or loss of motor function; and 13 cases of canal intrusion or cord compression. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors listed cement leakage as the most common complication following balloon kyphoplasty. They also listed infection, allergy and spinal cord or nerve root injury caused by incorrect needle placement as potential complications.\n\n# Other comments\n\nThe Medicines and Healthcare products Regulatory Agency has issued a safety notice on injectable polymeric cements used in percutaneous vertebroplasty, balloon kyphoplasty and pedicle screw augmentation.", 'Further information': "NICE has issued guidance on percutaneous vertebroplasty.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in NICE's interventional procedure overview of balloon kyphoplasty for vertebral compression fractures.\n\n# Information for patients\n\nNICE has produced information for patients and carers on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Other NICE recommendations on balloon kyphoplasty': 'Further recommendations have been made as part of the NICE guideline on metastatic spinal cord compression published in November 2008, as follows:\n\nVertebroplasty or kyphoplasty should be considered for patients who have vertebral metastases and no evidence of MSCC or spinal instability if they have either:\n\nmechanical pain resistant to analgesia, or\n\nvertebral body collapse.\n\nVertebroplasty or kyphoplasty for spinal metastases should only be performed after agreement between appropriate specialists including an oncologist, interventional radiologist, and spinal surgeon, and in facilities where there is good access to spinal surgery.\n\nClinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information can be found in the NICE guideline on metastatic spinal cord compression in adults. The intervention procedure guidance on balloon kyphoplasty for vertebral compression fractures remains current, and should be read in conjunction with the clinical guideline.'}	https://www.nice.org.uk/guidance/ipg166
2d75bfef2a457942f71e2099af1af59792e08b3d	nice	Retrograde urethral sphincterometry	Retrograde urethral sphincterometry # Guidance Current evidence suggests that there are no major safety concerns associated with retrograde urethral sphincterometry. However, there is a lack of evidence on the diagnostic utility of this procedure (that is, the extent to which knowledge of its results improves patients' outcomes) and it should be performed only in the context of good-quality research.# The procedure # Indications Stress urinary incontinence is the involuntary leakage of urine during exercise or certain movements such as coughing, sneezing and laughing. It is usually caused by weak or damaged muscles and connective tissues in the pelvic floor and urethral sphincter. Diagnosis of stress urinary incontinence is usually based on symptoms, examination and exclusion of underlying causes or comorbidity. Retrograde urethral sphincterometry measures the pressure needed to open, and just keep open, a closed urethra by the retrograde infusion of fluid. This has been proposed as an assessment of urethral function in women with symptoms of stress urinary incontinence. Established tests of urethral function include urethral pressure profilometry (UPP) and valsalva leak point pressure. Radiographic assessment of urethral function can be done using videocystourethrography. # Outline of the procedure Retrograde urethral sphincterometry (RUS) involves placing a cone-shaped device a short distance (about 5 mm) into the external urethral meatus. The device then infuses fluid at a controlled rate into the urethra. The pressure required to open the urethral sphincter is displayed on the device. # Efficacy Preliminary data on the use of this procedure in women with stress urinary incontinence found that there was a weak relationship between the results of this test and other standard tests. In a trial of 258 symptomatic women the mean retrograde urethral pressure as measured by RUS was 71 cm H2O, and the mean values were reported as decreasing with increasing symptom severity. In another study, the mean retrograde urethral pressure was found to be 112.6 cm H2O in 61 asymptomatic women. The impact of this procedure on patient outcomes is currently unclear. For more details, refer to the Sources of evidence. The Specialist Advisors noted that efficacy outcomes are yet to be established. # Safety In a study of 258 women, pain (2%) and dysuria (2%) were the two most commonly reported complaints. A total of 12 adverse events were noted in a study of 61 asymptomatic women who had RUS; these included lower back pain (2%), discomfort (2%), urethral pain (3%), dysuria (3%), urinary urgency (3%), urinary frequency (3%) and transient incontinence (3%). For more details, refer to the Sources of evidence. The Specialist Advisors noted urinary tract infection and mild discomfort as potential adverse events.# Further information # Sources of evidence The evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of retrograde urethral sphincoterometry. # Information for patients NICE has produced information for patients and carers on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence suggests that there are no major safety concerns associated with retrograde urethral sphincterometry. However, there is a lack of evidence on the diagnostic utility of this procedure (that is, the extent to which knowledge of its results improves patients' outcomes) and it should be performed only in the context of good-quality research.", 'The procedure': '# Indications\n\nStress urinary incontinence is the involuntary leakage of urine during exercise or certain movements such as coughing, sneezing and laughing. It is usually caused by weak or damaged muscles and connective tissues in the pelvic floor and urethral sphincter.\n\nDiagnosis of stress urinary incontinence is usually based on symptoms, examination and exclusion of underlying causes or comorbidity.\n\nRetrograde urethral sphincterometry measures the pressure needed to open, and just keep open, a closed urethra by the retrograde infusion of fluid. This has been proposed as an assessment of urethral function in women with symptoms of stress urinary incontinence.\n\nEstablished tests of urethral function include urethral pressure profilometry (UPP) and valsalva leak point pressure. Radiographic assessment of urethral function can be done using videocystourethrography.\n\n# Outline of the procedure\n\nRetrograde urethral sphincterometry (RUS) involves placing a cone-shaped device a short distance (about 5 mm) into the external urethral meatus. The device then infuses fluid at a controlled rate into the urethra. The pressure required to open the urethral sphincter is displayed on the device.\n\n# Efficacy\n\nPreliminary data on the use of this procedure in women with stress urinary incontinence found that there was a weak relationship between the results of this test and other standard tests. In a trial of 258 symptomatic women the mean retrograde urethral pressure as measured by RUS was 71 cm H2O, and the mean values were reported as decreasing with increasing symptom severity. In another study, the mean retrograde urethral pressure was found to be 112.6 cm H2O in 61 asymptomatic women.\n\nThe impact of this procedure on patient outcomes is currently unclear. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that efficacy outcomes are yet to be established.\n\n# Safety\n\nIn a study of 258 women, pain (2%) and dysuria (2%) were the two most commonly reported complaints. A total of 12 adverse events were noted in a study of 61 asymptomatic women who had RUS; these included lower back pain (2%), discomfort (2%), urethral pain (3%), dysuria (3%), urinary urgency (3%), urinary frequency (3%) and transient incontinence (3%). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted urinary tract infection and mild discomfort as potential adverse events.', 'Further information': '# Sources of evidence\n\nThe evidence considered by the interventional procedures advisory committee is described in the interventional procedure overview of retrograde urethral sphincoterometry.\n\n# Information for patients\n\nNICE has produced information for patients and carers on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg167
31de38c4b6e69b11dc497ca003a2353b593f1bb5	nice	Percutaneous radiofrequency ablation for atrial fibrillation	Percutaneous radiofrequency ablation for atrial fibrillation # Guidance Current evidence on the safety and efficacy of percutaneous radiofrequency ablation for atrial fibrillation appears adequate to support the use of this procedure in appropriately selected patients (see section 2.1.4) provided that normal arrangements are in place for audit and clinical governance. Clinicians should ensure that patients fully understand the potential complications, the likelihood of success and the risk of recurrent atrial fibrillation associated with this procedure. In addition, use of NICE's information for the public is recommended. This procedure should only be performed in specialist units and with arrangements for cardiac surgical support in the event of complications. This procedure should only be performed by cardiologists with extensive experience of other types of ablation procedures. The National Institute for Cardiovascular Outcomes Research runs the National Congenital Heart Disease Audit database and clinicians are encouraged to enter all patients undergoing percutaneous radiofrequency ablation for atrial fibrillation onto this database.# The procedure # Indications Atrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It may be classified as paroxysmal, persistent or permanent. Patients with atrial fibrillation may be asymptomatic or they may have symptoms including palpitations, dizziness, breathlessness and fatigue. They have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain. Atrial fibrillation usually occurs in the absence of structural heart disease. Conservative treatments include medication to control the heart rhythm and rate, electrical cardioversion and anticoagulation to prevent blood clots forming. Surgery for atrial fibrillation is usually performed at the same time as open heart surgery for another indication, such as for the correction of mitral valve disease. The conventional surgical approach, known as the Cox maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative methods of creating lesions in the atria by ablation have been developed using energy sources such as radiofrequency, microwave, cryotherapy and ultrasound. Percutaneous radiofrequency ablation is a treatment option for symptomatic patients with atrial fibrillation refractory to anti-arrhythmic drug therapy or where medical therapy is contraindicated because of co-morbidity or intolerance. # Outline of the procedure Percutaneous radiofrequency ablation is a minimally invasive procedure that is usually carried out under sedation. A catheter is inserted into the femoral vein and advanced into the heart, using X-ray fluoroscopic guidance to ensure correct positioning. An attachment at the tip of the catheter sends out radiofrequency energy, producing heat that damages the targeted area of the conduction pathway. Electrophysiological testing is undertaken before the procedure to identify and map the source of the abnormal electrical signals. Advanced imaging and mapping techniques that do not require fluoroscopy have also been developed for use in this procedure. Several different strategies may be used, including linear ablation in the left or right atrium and focal pulmonary vein to isolate triggers of atrial fibrillation that arise from within the pulmonary vein. This guidance does not refer to the procedure of atrioventricular node ablation and pacing. # Efficacy In a randomised controlled trial of 70 patients, recurrence of atrial fibrillation at 1 year follow-up was 13% (4/32) after radiofrequency ablation compared with 63% (22/35) after anti-arrhythmic medication (p < 0.001). There were also significantly fewer episodes of hospitalisation in the radiofrequency ablation group: 9% (3/32) and 54% (19/35) of patients, respectively (p < 0.001). Quality-of-life measurements at 6 months favoured the radiofrequency ablation treatment. In a smaller randomised controlled trial, frequency of symptoms decreased from a mean of 42.8 attacks per month at baseline to 0.9 attacks per month at 1 year in 14 patients after percutaneous radiofrequency ablation (p < 0.001). In a non-randomised comparative study of 1171 patients, 78% of patients treated with radiofrequency ablation were estimated to be free of atrial fibrillation at 3 years, compared with 37% of patients treated with medication (p < 0.001). Patients receiving percutaneous radiofrequency ablation had a 54% reduction in risk of death compared with those receiving medication (p < 0.001). A large survey reported that 76% (6644/8745) of treated patients had resolution of symptoms of atrial fibrillation after a median follow-up of 12 months (this proportion ranged from 22% to 91% among different centres). For more details, refer to the Sources of evidence. The Specialist Advisors noted the lack of long-term data. # Safety A complication rate of 6% (524/8745) was reported in the survey of 8745 patients who had undergone percutaneous radiofrequency ablation for atrial fibrillation. The most significant complications reported in this study were four early deaths (< 1%), 20 strokes (< 1%), 47 transient ischaemic attacks (1%), 117 cases of pulmonary vein stenosis (1%), 107 episodes of cardiac tamponade (1%) and 37 cases of arteriovenous fistula (< 1%). In two comparative studies of 1171 and 30 patients, complications specific to percutaneous radiofrequency ablation included cardiac tamponade in less than 1% (4/589) of patients, stroke in 7% (1/14) and groin haematoma in 7% (1/14). Two of the studies also reported that 2% and 4% of patients (12/589 and 340/8745, respectively) developed atypical atrial flutter of new onset after undergoing percutaneous radiofrequency ablation. In a case series of 632 procedures a cardiac perforation rate of 2% (15 procedures) was reported, each case requiring pericardiocentesis: all the patients affected survived. For more details, refer to the Sources of evidence. The Specialist Advisors listed the potential adverse events as stroke, cardiac tamponade, atrio-oesophageal fistula and pulmonary vein stenosis.# Further information NICE has issued guidance on radiofrequency ablation, microwave ablation and cryoablation for atrial fibrillation in association with other cardiac surgery. NICE has also developed interventional procedures guidance on high-intensity focused ultrasound ablation for atrial fibrillation as an associated procedure with other cardiac surgery and a guideline on the management of atrial fibrillation. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the interventional procedure overview of percutaneous radiofrequency catheter ablation for atrial fibrillation. # Information for patients NICE has produced information for patients and carers on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of percutaneous radiofrequency ablation for atrial fibrillation appears adequate to support the use of this procedure in appropriately selected patients (see section 2.1.4) provided that normal arrangements are in place for audit and clinical governance.\n\nClinicians should ensure that patients fully understand the potential complications, the likelihood of success and the risk of recurrent atrial fibrillation associated with this procedure. In addition, use of NICE's information for the public is recommended.\n\nThis procedure should only be performed in specialist units and with arrangements for cardiac surgical support in the event of complications.\n\nThis procedure should only be performed by cardiologists with extensive experience of other types of ablation procedures.\n\nThe\xa0National Institute for Cardiovascular Outcomes Research runs the National Congenital Heart Disease Audit database and clinicians are encouraged to enter all patients undergoing percutaneous radiofrequency ablation for atrial fibrillation onto this database.", 'The procedure': '# Indications\n\nAtrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It may be classified as paroxysmal, persistent or permanent. Patients with atrial fibrillation may be asymptomatic or they may have symptoms including palpitations, dizziness, breathlessness and fatigue. They have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain.\n\nAtrial fibrillation usually occurs in the absence of structural heart disease.\n\nConservative treatments include medication to control the heart rhythm and rate, electrical cardioversion and anticoagulation to prevent blood clots forming. Surgery for atrial fibrillation is usually performed at the same time as open heart surgery for another indication, such as for the correction of mitral valve disease. The conventional surgical approach, known as the Cox maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative methods of creating lesions in the atria by ablation have been developed using energy sources such as radiofrequency, microwave, cryotherapy and ultrasound.\n\nPercutaneous radiofrequency ablation is a treatment option for symptomatic patients with atrial fibrillation refractory to anti-arrhythmic drug therapy or where medical therapy is contraindicated because of co-morbidity or intolerance.\n\n# Outline of the procedure\n\nPercutaneous radiofrequency ablation is a minimally invasive procedure that is usually carried out under sedation. A catheter is inserted into the femoral vein and advanced into the heart, using X-ray fluoroscopic guidance to ensure correct positioning. An attachment at the tip of the catheter sends out radiofrequency energy, producing heat that damages the targeted area of the conduction pathway. Electrophysiological testing is undertaken before the procedure to identify and map the source of the abnormal electrical signals. Advanced imaging and mapping techniques that do not require fluoroscopy have also been developed for use in this procedure.\n\nSeveral different strategies may be used, including linear ablation in the left or right atrium and focal pulmonary vein to isolate triggers of atrial fibrillation that arise from within the pulmonary vein. This guidance does not refer to the procedure of atrioventricular node ablation and pacing.\n\n# Efficacy\n\nIn a randomised controlled trial of 70 patients, recurrence of atrial fibrillation at 1 year follow-up was 13% (4/32) after radiofrequency ablation compared with 63% (22/35) after anti-arrhythmic medication (p < 0.001). There were also significantly fewer episodes of hospitalisation in the radiofrequency ablation group: 9% (3/32) and 54% (19/35) of patients, respectively (p < 0.001). Quality-of-life measurements at 6 months favoured the radiofrequency ablation treatment. In a smaller randomised controlled trial, frequency of symptoms decreased from a mean of 42.8 attacks per month at baseline to 0.9 attacks per month at 1 year in 14 patients after percutaneous radiofrequency ablation (p < 0.001).\n\nIn a non-randomised comparative study of 1171 patients, 78% of patients treated with radiofrequency ablation were estimated to be free of atrial fibrillation at 3 years, compared with 37% of patients treated with medication (p < 0.001). Patients receiving percutaneous radiofrequency ablation had a 54% reduction in risk of death compared with those receiving medication (p < 0.001).\n\nA large survey reported that 76% (6644/8745) of treated patients had resolution of symptoms of atrial fibrillation after a median follow-up of 12 months (this proportion ranged from 22% to 91% among different centres). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted the lack of long-term data.\n\n# Safety\n\nA complication rate of 6% (524/8745) was reported in the survey of 8745 patients who had undergone percutaneous radiofrequency ablation for atrial fibrillation. The most significant complications reported in this study were four early deaths (< 1%), 20 strokes (< 1%), 47 transient ischaemic attacks (1%), 117 cases of pulmonary vein stenosis (1%), 107 episodes of cardiac tamponade (1%) and 37 cases of arteriovenous fistula (< 1%).\n\nIn two comparative studies of 1171 and 30 patients, complications specific to percutaneous radiofrequency ablation included cardiac tamponade in less than 1% (4/589) of patients, stroke in 7% (1/14) and groin haematoma in 7% (1/14).\n\nTwo of the studies also reported that 2% and 4% of patients (12/589 and 340/8745, respectively) developed atypical atrial flutter of new onset after undergoing percutaneous radiofrequency ablation. In a case series of 632 procedures a cardiac perforation rate of 2% (15 procedures) was reported, each case requiring pericardiocentesis: all the patients affected survived. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors listed the potential adverse events as stroke, cardiac tamponade, atrio-oesophageal fistula and pulmonary vein stenosis.', 'Further information': 'NICE has issued guidance on radiofrequency ablation, microwave ablation and cryoablation for atrial fibrillation in association with other cardiac surgery.\n\nNICE has also developed interventional procedures guidance on high-intensity focused ultrasound ablation for atrial fibrillation as an associated procedure with other cardiac surgery and a guideline on the management of atrial fibrillation.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the interventional procedure overview of percutaneous radiofrequency catheter ablation for atrial fibrillation.\n\n# Information for patients\n\nNICE has produced information for patients and carers on this procedure. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg168
f84ec84688a6f0325fc1369170e58ec64780b517	nice	Endometrial cryotherapy for menorrhagia	Endometrial cryotherapy for menorrhagia # Guidance Limited short-term evidence on the safety and efficacy of endometrial cryotherapy for menorrhagia appears adequate to support the use of this procedure in carefully selected patients provided that normal arrangements are in place for consent, audit and clinical governance. Clinicians should ensure that patients understand that there are alternative treatment options with different likelihoods of achieving complete amenorrhea or normal periods. Appropriate patient selection and patient choice are both important. In addition, use of the Institute's information for the public is recommended.# The procedure # Indications Menorrhagia is heavy cyclical menstrual bleeding over several consecutive cycles in a woman of reproductive years. Menorrhagia is clinically defined as a total menstrual blood loss of more than 80 ml per menstruation. Menorrhagia has adverse implications for quality of life. Women with menorrhagia may have difficulties with daily activities such as work, family life and social activities. Many women report anxiety, depression, embarrassment and problems in their sex lives as a result of menorrhagia. Anaemia is also common among women with menorrhagia, and this may further impair quality of life. Patients are usually treated with medication before surgery is considered. This may be administered orally or released into the lining of the uterus (endometrium) by a special intrauterine device. Historically, hysterectomy has been the standard surgical option for women with menorrhagia who no longer desire to maintain fertility. Alternatives to hysterectomy are minimally invasive procedures that may be performed using a hysteroscope. These include transcervical endometrial resection or destruction of the endometrium with lasers, electrocautery, radiofrequency waves or heated saline. Non-hysteroscopic procedures include destroying the endometrium using heated saline, heated balloons, lasers, radiofrequency waves or microwaves. Non-hysteroscopic procedures are often carried out under local anaesthesia as a day admission. # Outline of the procedure Endometrial cryotherapy is a non-hysteroscopic procedure that uses cold temperatures to freeze and destroy the endometrium. It can be performed under general, regional or local anaesthesia, although sometimes no anaesthesia is needed. A cryoprobe is inserted into the fundus of the uterus and cooled by perfusing it with either liquid nitrogen or a compressed gas mixture. The tip of the probe is placed first in one cornu of the uterus and then in the other, to generate an iceball that destroys the endometrial tissue. Each freeze cycle is followed by a heat (thaw) cycle, which allows the probe to be removed. Additional freeze/thaw cycles may be carried out if necessary. # Efficacy In a randomised controlled trial (RCT), rates of treatment success as assessed by the reduction of menstrual bleeding to a pictorial blood loss assessment chart (PBAC) score of 75 or less in the absence of retreatment at 12 months were 67% (130/193 patients) and 73% (63/86 patients) in the cryotherapy and electroablation groups, respectively. The proportion of patients in the cryotherapy and electroablation groups at 12 months (not analysed by intention to treat) with menorrhagia (PBAC greater than 100) were 12.2% and 6.9%, respectively, and with amenorrhoea (PBAC score 0) were 27.6% and 55.6%, respectively. In a case series of 67 women, none were amenorrhoeic during more than 3 months of follow-up (up to 18 months). Patient satisfaction ranged from 67% (22/33) at up to 18 months' follow-up in the case series, to 91% at 24 months in the RCT. Retreatment at 24 months was reported for 10% (18/186) of patients who had cryotherapy in the RCT: 7% (13/186) of patients had a hysterectomy and 3% (5/186) of patients had repeat cryoablation. For more details, refer to the Sources of evidence. The Specialist Advisors stated that the evidence from RCTs is limited, and that this procedure was one of a number of ablation techniques that uses different energy. # Safety In the RCT, uterine perforation occurred during sounding before treatment in 0.5% (1/186) of patients, and there were three serious adverse events that occurred more than 15 days after the procedure (and within 12 months). These were severe abdominal cramping (two patients) and severe vaginal bleeding (one patient). Other adverse events reported at up to 12 months' follow-up included: abdominal or pelvic pain/cramping in 14% (26/186) of patients; uterine cramping in 4% (7/186); vaginal infection in 4% (7/186); hot flushes in 2% (3/186); urinary tract infection in 1% (2/186); and nausea and vomiting in 0.5% (1/186). In the prospective case series of 67 women, adverse events reported immediately after the procedure included urinary frequency or urgency (100%), moderate pelvic pain, dysuria and vaginal discharge (the numbers of patients were not well reported). Other less commonly reported adverse events were prolonged tiredness and perimenopausal symptoms. The adverse events reported in the US Food and Drug Administration Center for Devices and Radiological Health MAUDE database included excessive bleeding, uterine perforation bowel injury and stenosis of the cervix. For more details, refer to the Sources of evidence. The Specialist Advisors stated that the procedure appears to be safe, but there are no data available on the incidence of major complications. The theoretical adverse events include thermal injury to the cervix and vagina. Anecdotal adverse events include persistent discharge and endometritis. # Other comments The Committee noted that there are no long-term follow-up data.# Further information The Institute has issued guidance on the following procedures: microwave endometrial ablation, photodynamic endometrial ablation, balloon thermal endometrial ablation, free fluid thermal endometrial ablation and impedance-controlled endometrial ablation. Andrew DillonChief ExecutiveMarch 2006 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of endometrial cryotherapy for menorrhagia', July 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Limited short-term evidence on the safety and efficacy of endometrial cryotherapy for menorrhagia appears adequate to support the use of this procedure in carefully selected patients provided that normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians should ensure that patients understand that there are alternative treatment options with different likelihoods of achieving complete amenorrhea or normal periods. Appropriate patient selection and patient choice are both important. In addition, use of the Institute's information for the public is recommended.", 'The procedure': "# Indications\n\nMenorrhagia is heavy cyclical menstrual bleeding over several consecutive cycles in a woman of reproductive years. Menorrhagia is clinically defined as a total menstrual blood loss of more than 80 ml per menstruation.\n\nMenorrhagia has adverse implications for quality of life. Women with menorrhagia may have difficulties with daily activities such as work, family life and social activities. Many women report anxiety, depression, embarrassment and problems in their sex lives as a result of menorrhagia. Anaemia is also common among women with menorrhagia, and this may further impair quality of life.\n\nPatients are usually treated with medication before surgery is considered. This may be administered orally or released into the lining of the uterus (endometrium) by a special intrauterine device. Historically, hysterectomy has been the standard surgical option for women with menorrhagia who no longer desire to maintain fertility. Alternatives to hysterectomy are minimally invasive procedures that may be performed using a hysteroscope. These include transcervical endometrial resection or destruction of the endometrium with lasers, electrocautery, radiofrequency waves or heated saline. Non-hysteroscopic procedures include destroying the endometrium using heated saline, heated balloons, lasers, radiofrequency waves or microwaves. Non-hysteroscopic procedures are often carried out under local anaesthesia as a day admission.\n\n# Outline of the procedure\n\nEndometrial cryotherapy is a non-hysteroscopic procedure that uses cold temperatures to freeze and destroy the endometrium. It can be performed under general, regional or local anaesthesia, although sometimes no anaesthesia is needed. A cryoprobe is inserted into the fundus of the uterus and cooled by perfusing it with either liquid nitrogen or a compressed gas mixture. The tip of the probe is placed first in one cornu of the uterus and then in the other, to generate an iceball that destroys the endometrial tissue. Each freeze cycle is followed by a heat (thaw) cycle, which allows the probe to be removed. Additional freeze/thaw cycles may be carried out if necessary.\n\n# Efficacy\n\nIn a randomised controlled trial (RCT), rates of treatment success as assessed by the reduction of menstrual bleeding to a pictorial blood loss assessment chart (PBAC) score of 75 or less in the absence of retreatment at 12 months were 67% (130/193 patients) and 73% (63/86 patients) in the cryotherapy and electroablation groups, respectively. The proportion of patients in the cryotherapy and electroablation groups at 12 months (not analysed by intention to treat) with menorrhagia (PBAC greater than 100) were 12.2% and 6.9%, respectively, and with amenorrhoea (PBAC score 0) were 27.6% and 55.6%, respectively. In a case series of 67 women, none were amenorrhoeic during more than 3 months of follow-up (up to 18 months).\n\nPatient satisfaction ranged from 67% (22/33) at up to 18 months' follow-up in the case series, to 91% at 24 months in the RCT.\n\nRetreatment at 24 months was reported for 10% (18/186) of patients who had cryotherapy in the RCT: 7% (13/186) of patients had a hysterectomy and 3% (5/186) of patients had repeat cryoablation. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that the evidence from RCTs is limited, and that this procedure was one of a number of ablation techniques that uses different energy.\n\n# Safety\n\nIn the RCT, uterine perforation occurred during sounding before treatment in 0.5% (1/186) of patients, and there were three serious adverse events that occurred more than 15 days after the procedure (and within 12 months). These were severe abdominal cramping (two patients) and severe vaginal bleeding (one patient). Other adverse events reported at up to 12 months' follow-up included: abdominal or pelvic pain/cramping in 14% (26/186) of patients; uterine cramping in 4% (7/186); vaginal infection in 4% (7/186); hot flushes in 2% (3/186); urinary tract infection in 1% (2/186); and nausea and vomiting in 0.5% (1/186).\n\nIn the prospective case series of 67 women, adverse events reported immediately after the procedure included urinary frequency or urgency (100%), moderate pelvic pain, dysuria and vaginal discharge (the numbers of patients were not well reported). Other less commonly reported adverse events were prolonged tiredness and perimenopausal symptoms.\n\nThe adverse events reported in the US Food and Drug Administration Center for Devices and Radiological Health MAUDE database included excessive bleeding, uterine perforation bowel injury and stenosis of the cervix. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that the procedure appears to be safe, but there are no data available on the incidence of major complications. The theoretical adverse events include thermal injury to the cervix and vagina. Anecdotal adverse events include persistent discharge and endometritis.\n\n# Other comments\n\nThe Committee noted that there are no long-term follow-up data.", 'Further information': "The Institute has issued guidance on the following procedures: microwave endometrial ablation, photodynamic endometrial ablation, balloon thermal endometrial ablation, free fluid thermal endometrial ablation and impedance-controlled endometrial ablation.\n\nAndrew DillonChief ExecutiveMarch 2006\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of endometrial cryotherapy for menorrhagia', July 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg157
eb03d0ff341187fbd02bd95fbea0f14cbf8bae77	nice	Laparoscopic retroperitoneal lymph node dissection for testicular cancer	Laparoscopic retroperitoneal lymph node dissection for testicular cancer # Guidance Current evidence on the efficacy of laparoscopic retroperitoneal lymph node dissection is limited and there are safety concerns about the procedure. It should therefore not be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake laparoscopic retroperitoneal lymph node dissection for testicular cancer should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the potential serious complications associated with this procedure and provide them with clear written information. In addition, use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having laparoscopic retroperitoneal lymph node dissection for testicular cancer. This procedure is technically demanding and should only be performed in units with experience in open and laparoscopic techniques, and in the context of a multidisciplinary team. Publication of safety and efficacy outcomes will be useful. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Patients with testicular cancer who have had the cancerous testicle removed may require resection of lymph nodes, depending on the type and extent of disease as defined by imaging and blood markers. The standard method for retroperitoneal lymph node dissection is an open procedure through an additional incision. A modification to the standard approach is nerve-sparing retroperitoneal lymph node dissection, in which the lumbar postganglionic nerves are identified and preserved in order to preserve antegrade ejaculation. A laparoscopic approach has the theoretical advantages of reduced morbidity and shorter recovery time. # Outline of the procedure The lymph nodes and lymph tissue that drains the testicle are removed laparoscopically, through small incisions in the abdomen. The number of nodes removed can vary from fewer than ten to over 50, and the limits of excision are defined by a predetermined template. # Efficacy No local cancer recurrence was reported in a case series of 20 patients followed up for 10 months. In another case series, contralateral retroperitoneal recurrence was reported in 2% (1/65) of patients with stage I cancer at 45 months, but no relapse was recorded among 47 patients with stage II disease at 35 months. In another case series, 97% (179/185) of patients were relapse-free at 54–58 months' follow-up. In a comparative trial, the mean postoperative hospital stay was 4 days for patients who had had the laparoscopic procedure. Patients who had had open surgery stayed in hospital for mean 10.6 days. In an historically controlled study, the mean operative times for the first 14 patients undergoing laparoscopic retroperitoneal lymph node dissection were 9.3 hours for right-sided tumours and 5.8 hours for left-sided tumours. For the next 15 patients, the operating times were 5.9 and 4.0 hours, respectively, which were similar to the 4.3 and 4.1 hours taken for the open procedure (30 patients). In other case series, the mean operative times for the laparoscopic procedure were 3.7–6.0 hours; they varied according to operator experience and stage of the cancers. The rate of conversion to open surgery in case series ranged from 3% (5/185) to 10% (2/20). For more details, refer to the Sources of evidence. The Specialist Advisors noted that there is some controversy about whether the procedure should be used for diagnosis in early stage cancer. # Safety In an historically controlled study, major bleeding occurred during the procedure in 3% (1/29) of patients, and during 13% (4/30) of open retroperitoneal lymph node dissections. In case series, intraoperative haemorrhage occurred in 5% (1/20) to 18% (9/49) of patients with stage I and stage II disease, respectively. Retrograde ejaculation was reported in 0% (0/29 and 0/20) to 2% (3/185) of patients following laparoscopic retroperitoneal lymph node dissection. In the controlled study and case series, the incidence of lymphocoele was 4% (3/76) to 9% (16/185): in most cases this was minor and asymptomatic. Other complications reported across the studies included: pressure sores in 14% (2/14) of patients; gonadal vessel injury in 10% (2/20); subcutaneous lymphoedema in 7% (1/15); chylous ascites in 5% (9/185) (no cases were reported following the introduction of a new dietary regimen); injury to the inferior mesenteric artery in 5% (1/20); renal artery or colon injury in 1% (2/185); and transient irritation of the genitofemoral nerve in 1% (1/76). For more details, refer to the Sources of evidence. The Specialist Advisors noted that the theoretical adverse events included vascular injury, bowel perforation, incomplete resection, haemorrhage, and local or port-site recurrence. They also noted that there may be increased risks when dissecting large nodal masses that encircle the aorta or vena cava. Andrew DillonChief ExecutiveMarch 2006# Further information # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of laparoscopic retroperitoneal lymph node dissection for testicular cancer', May 2005.# Changes since publication The guidance was considered for reassessment in March 2009 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the efficacy of laparoscopic retroperitoneal lymph node dissection is limited and there are safety concerns about the procedure. It should therefore not be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake laparoscopic retroperitoneal lymph node dissection for testicular cancer should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the potential serious complications associated with this procedure and provide them with clear written information. In addition, use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having laparoscopic retroperitoneal lymph node dissection for testicular cancer.\n\nThis procedure is technically demanding and should only be performed in units with experience in open and laparoscopic techniques, and in the context of a multidisciplinary team.\n\nPublication of safety and efficacy outcomes will be useful. The Institute may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nPatients with testicular cancer who have had the cancerous testicle removed may require resection of lymph nodes, depending on the type and extent of disease as defined by imaging and blood markers.\n\nThe standard method for retroperitoneal lymph node dissection is an open procedure through an additional incision. A modification to the standard approach is nerve-sparing retroperitoneal lymph node dissection, in which the lumbar postganglionic nerves are identified and preserved in order to preserve antegrade ejaculation. A laparoscopic approach has the theoretical advantages of reduced morbidity and shorter recovery time.\n\n# Outline of the procedure\n\nThe lymph nodes and lymph tissue that drains the testicle are removed laparoscopically, through small incisions in the abdomen. The number of nodes removed can vary from fewer than ten to over 50, and the limits of excision are defined by a predetermined template.\n\n# Efficacy\n\nNo local cancer recurrence was reported in a case series of 20 patients followed up for 10 months. In another case series, contralateral retroperitoneal recurrence was reported in 2% (1/65) of patients with stage I cancer at 45 months, but no relapse was recorded among 47 patients with stage II disease at 35 months. In another case series, 97% (179/185) of patients were relapse-free at 54–58 months' follow-up.\n\nIn a comparative trial, the mean postoperative hospital stay was 4 days for patients who had had the laparoscopic procedure. Patients who had had open surgery stayed in hospital for mean 10.6 days.\n\nIn an historically controlled study, the mean operative times for the first 14 patients undergoing laparoscopic retroperitoneal lymph node dissection were 9.3 hours for right-sided tumours and 5.8 hours for left-sided tumours. For the next 15 patients, the operating times were 5.9 and 4.0 hours, respectively, which were similar to the 4.3 and 4.1 hours taken for the open procedure (30 patients). In other case series, the mean operative times for the laparoscopic procedure were 3.7–6.0 hours; they varied according to operator experience and stage of the cancers.\n\nThe rate of conversion to open surgery in case series ranged from 3% (5/185) to 10% (2/20). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that there is some controversy about whether the procedure should be used for diagnosis in early stage cancer.\n\n# Safety\n\nIn an historically controlled study, major bleeding occurred during the procedure in 3% (1/29) of patients, and during 13% (4/30) of open retroperitoneal lymph node dissections. In case series, intraoperative haemorrhage occurred in 5% (1/20) to 18% (9/49) of patients with stage I and stage II disease, respectively.\n\nRetrograde ejaculation was reported in 0% (0/29 and 0/20) to 2% (3/185) of patients following laparoscopic retroperitoneal lymph node dissection. In the controlled study and case series, the incidence of lymphocoele was 4% (3/76) to 9% (16/185): in most cases this was minor and asymptomatic.\n\nOther complications reported across the studies included: pressure sores in 14% (2/14) of patients; gonadal vessel injury in 10% (2/20); subcutaneous lymphoedema in 7% (1/15); chylous ascites in 5% (9/185) (no cases were reported following the introduction of a new dietary regimen); injury to the inferior mesenteric artery in 5% (1/20); renal artery or colon injury in 1% (2/185); and transient irritation of the genitofemoral nerve in 1% (1/76). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that the theoretical adverse events included vascular injury, bowel perforation, incomplete resection, haemorrhage, and local or port-site recurrence. They also noted that there may be increased risks when dissecting large nodal masses that encircle the aorta or vena cava.\n\nAndrew DillonChief ExecutiveMarch 2006", 'Further information': "# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of laparoscopic retroperitoneal lymph node dissection for testicular cancer', May 2005.", 'Changes since publication': 'The guidance was considered for reassessment in March 2009 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg158
e8c7301becdb06aa2dfd62d877fcd204740c0237	nice	Stimulated graciloplasty for faecal incontinence	Stimulated graciloplasty for faecal incontinence # Guidance Current evidence on the safety and efficacy of stimulated graciloplasty for faecal incontinence is limited, but appears sufficient to support the use of this procedure for carefully selected patients in whom other treatments have failed or are contraindicated, provided that the normal arrangements are in place for consent, audit and clinical governance. This procedure should be performed only in specialist units by clinicians with specific training and experience in the assessment and treatment of faecal incontinence.# The procedure # Indications Stimulated graciloplasty is used to treat refractory faecal incontinence (for example, anorectal atresia) as an alternative to colostomy. Other approaches aimed at establishing continence are insertion of an artificial anal sphincter and sacral nerve stimulation. # Outline of the procedure Stimulated graciloplasty involves creating a new anal sphincter using transposed gracilis muscle. Electrodes are implanted in the transposed muscle and connected to an electric pulse generator implanted in the abdominal wall. A continuous current from the pulse generator gradually alters the character of the gracilis muscle fibres. The procedure can be performed in one or two stages. In the latter case, the muscle wrapping precedes the electrode implantation stage by a few weeks. # Efficacy A systematic review of 37 studies of graciloplasty found that between 42% and 85% of patients became continent after the procedure (different definitions of continence were used and continence was assessed at different time points in the studies). A controlled study found that at 24 months, frequency of incontinence had significantly improved from baseline in 48 patients who had undergone graciloplasty (p < 0.0001); there was no improvement during this period in patients who were not offered surgery. A case series reported successful outcomes in 72% (144/200) of patients, with 5-year follow-up. A controlled trial found that quality of life improved more in patients treated with graciloplasty (n = 46) than in those not offered surgery who were being medically managed (n = 40). The following scales were used to assess quality of life: the Cleveland Clinic Faecal Incontinence Scale (p = 0.001); the Hospital Anxiety and Depression Scale for anxiety (p = 0.03) and depression (p = 0.05); and a validated study-specific scale for psychological wellbeing (p < 0.0001) and lifestyle characteristics (p < 0.0001). In a case series of 129 patients who had graciloplasty, patients' quality of life was significantly improved on the SF-36 scale for physical and social functioning at 12 months' follow-up. For more details, refer to the Sources of evidence section. The Specialist Advisors suggested that this procedure has been largely superseded by sacral nerve stimulation. # Safety The most common complication of stimulated graciloplasty is wound infection. In a systematic review that included 403 patients assessed for safety outcomes, the overall rate of infection was 28%. In a case series of 121 patients, serious infection needing hospitalisation and/or surgery was reported in 15% of patients, and in another series it occurred in 14% (17/123) of patients. Electrical or technical problems with the pulse generator leading to hospitalisation occurred in 48% (23/48) of patients who had undergone graciloplasty in a controlled trial at 42 months' follow-up. In a case series of 123 patients, 3 patients (2%) had a deep vein thrombosis and one patient died following a pulmonary embolism 3 weeks after surgery. In a comparative study 69% (33/48) of patients had evacuation difficulties or pain requiring hospitalisation following graciloplasty. Disturbed evacuation was reported in 16% (32/200) of patients in a prospective case series. For more details, refer to the Sources of evidence section. The Specialist Advisors noted that the main reported adverse events were related to the pulse generator, particularly the risk of infection (both in the short and the long term).# Further information The Institute has produced guidance on sacral nerve stimulation for faecal incontinence. Andrew DillonChief ExecutiveMarch 2006 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of stimulated graciloplasty', June 2005. # Information for the public NICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of stimulated graciloplasty for faecal incontinence is limited, but appears sufficient to support the use of this procedure for carefully selected patients in whom other treatments have failed or are contraindicated, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThis procedure should be performed only in specialist units by clinicians with specific training and experience in the assessment and treatment of faecal incontinence.', 'The procedure': "# Indications\n\nStimulated graciloplasty is used to treat refractory faecal incontinence (for example, anorectal atresia) as an alternative to colostomy. Other approaches aimed at establishing continence are insertion of an artificial anal sphincter and sacral nerve stimulation.\n\n# Outline of the procedure\n\nStimulated graciloplasty involves creating a new anal sphincter using transposed gracilis muscle. Electrodes are implanted in the transposed muscle and connected to an electric pulse generator implanted in the abdominal wall. A continuous current from the pulse generator gradually alters the character of the gracilis muscle fibres.\n\nThe procedure can be performed in one or two stages. In the latter case, the muscle wrapping precedes the electrode implantation stage by a few weeks.\n\n# Efficacy\n\nA systematic review of 37 studies of graciloplasty found that between 42% and 85% of patients became continent after the procedure (different definitions of continence were used and continence was assessed at different time points in the studies). A controlled study found that at 24 months, frequency of incontinence had significantly improved from baseline in 48 patients who had undergone graciloplasty (p < 0.0001); there was no improvement during this period in patients who were not offered surgery. A case series reported successful outcomes in 72% (144/200) of patients, with 5-year follow-up.\n\nA controlled trial found that quality of life improved more in patients treated with graciloplasty (n = 46) than in those not offered surgery who were being medically managed (n = 40). The following scales were used to assess quality of life: the Cleveland Clinic Faecal Incontinence Scale (p = 0.001); the Hospital Anxiety and Depression Scale for anxiety (p = 0.03) and depression (p = 0.05); and a validated study-specific scale for psychological wellbeing (p < 0.0001) and lifestyle characteristics (p < 0.0001). In a case series of 129 patients who had graciloplasty, patients' quality of life was significantly improved on the SF-36 scale for physical and social functioning at 12 months' follow-up. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors suggested that this procedure has been largely superseded by sacral nerve stimulation.\n\n# Safety\n\nThe most common complication of stimulated graciloplasty is wound infection. In a systematic review that included 403 patients assessed for safety outcomes, the overall rate of infection was 28%. In a case series of 121 patients, serious infection needing hospitalisation and/or surgery was reported in 15% of patients, and in another series it occurred in 14% (17/123) of patients.\n\nElectrical or technical problems with the pulse generator leading to hospitalisation occurred in 48% (23/48) of patients who had undergone graciloplasty in a controlled trial at 42 months' follow-up. In a case series of 123 patients, 3 patients (2%) had a deep vein thrombosis and one patient died following a pulmonary embolism 3 weeks after surgery.\n\nIn a comparative study 69% (33/48) of patients had evacuation difficulties or pain requiring hospitalisation following graciloplasty. Disturbed evacuation was reported in 16% (32/200) of patients in a prospective case series. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors noted that the main reported adverse events were related to the pulse generator, particularly the risk of infection (both in the short and the long term).", 'Further information': "The Institute has produced guidance on sacral nerve stimulation for faecal incontinence.\n\nAndrew DillonChief ExecutiveMarch 2006\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of stimulated graciloplasty', June 2005.\n\n# Information for the public\n\nNICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg159
02382aed182043ab675a9ddc1d6bebaf0af960cc	nice	High dose rate brachytherapy for carcinoma of the cervix	High dose rate brachytherapy for carcinoma of the cervix # Guidance Current evidence on the safety and efficacy of high dose rate brachytherapy for carcinoma of the cervix appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Clinicians should ensure that patients have appropriate counselling and pain management. In addition, use of the Institute's information for the public is recommended.# The procedure # Indications and current treatments There are two main types of cancer of the cervix. The most common, squamous cell carcinoma, usually develops from the cells which cover the outer surface of the cervix (the ectocervix). The other, adenocarcinoma, usually develops from the glandular cells that line the cervical canal (the endocervix). The stage of the cancer is defined by its size and by the extent of spread beyond the cervix. The most common symptoms of cervical cancer are abnormal vaginal bleeding or discharge and discomfort during intercourse. Cancer of the cervix can be treated with surgery, radiotherapy, chemotherapy or a combination of these treatments. Surgery is often the main treatment for cancer of the cervix in its early stages (where cancer is found only in the cervix). Chemotherapy is occasionally used before surgery, shrinking the cancer to make the operation simpler. However, it is mainly given in combination with radiotherapy, either as a primary therapy or after surgery. Brachytherapy can be given in low, medium or high dose rates. Low dose rate brachytherapy delivers radiation slowly. In order to administer a radiation dose that will eliminate the cancer, applicators need to be in place in the vagina for 2 to 3 days. # Outline of the procedure High dose rate (HDR) brachytherapy was developed to reduce the radiation hazard to staff, and to reduce the length of inpatient treatment, with a requirement for isolation of the patient. HDR brachytherapy may be used for palliation of advanced disease, but this guidance refers only to HDR brachytherapy used with curative intent. Applicators are put in place in the cervix and connected to an afterloading machine which delivers radiation at a high dose rate, typically for a few minutes. The treatment is often repeated several times, a few days apart, on an outpatient basis. This procedure gives a high dose of radiation to the cervix and the adjacent area, but a low dose to tissues and organs more than a few centimetres away. Practically all HDR brachytherapy is given in conjunction with external-beam radiation therapy. # Efficacy In two randomised controlled trials (RCTs) that compared patients treated with HDR and those treated with low dose rate (LDR) brachytherapy, the overall survival (across all stages of disease) with HDR was 68% and 54% at 3 and 5 years follow-up, respectively, compared with 71% and 55% after LDR brachytherapy. These differences were not significant. In an RCT, the overall 5-year survival (across all stages) in 31 patients who had received HDR brachytherapy was 61%, compared with 63% in 29 patients who had received medium dose rate (MDR) treatment. In the same study, local disease-free survival was achieved in 67% of patients who had received HDR brachytherapy compared with 78% in the MDR-treated patients. Distant metastases occurred in 6% (15/236), 19% (372/1992) and 22% (43/200 and 25/112) of HDR-treated patients in RCTs and a case series. Where the outcome was reported, local recurrence occurred in 6% (7/112), 21% (415/1992) and 22% (51/236) of HDR-treated patients, with follow-up ranging from 3 to 10 years. For more details, refer to the Sources of evidence section. Some of the Specialist Advisors stated that HDR brachytherapy had equivalent efficacy to LDR brachytherapy. # Safety In a large case series of 1992 patients, with a median 8-year follow-up, the overall bowel and bladder complication rate was 35%. Radiation Therapy Oncology Group grade 3 or 4 complications occurred in 7% of patients. In an RCT that compared HDR and MDR brachytherapy, the grade 2 complication rate among HDR-treated patients was 13% (4/31). In the MDR arm, there were grade 2 complications in 3% (1/29) of patients. Where reported separately, rectal complications (all grades) affected 4% to 20% (22/112) of patients, and bladder complications affected 4% (8/200) of patients. Serious complications such as bowel obstruction, severe rectal bleeding and stenosis, which required subsequent surgery, occurred in 2% and 6% (11/200) of patients in two case series. For more details, refer to the Sources of evidence section. The Specialist Advisors reported that complications include diarrhoea, bleeding, colitis and cystitis, and also fistulae requiring surgery. They noted the possibility of long-term problems affecting the bowel, bladder and rectum. # Other comments Consultees highlighted that this procedure can be very painful. Andrew DillonChief ExecutiveMarch 2006# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of high dose rate (HDR) brachytherapy for carcinoma of the cervix', August 2005. # Information for the public NICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of high dose rate brachytherapy for carcinoma of the cervix appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians should ensure that patients have appropriate counselling and pain management. In addition, use of the Institute's information for the public is recommended.", 'The procedure': '# Indications and current treatments\n\nThere are two main types of cancer of the cervix. The most common, squamous cell carcinoma, usually develops from the cells which cover the outer surface of the cervix (the ectocervix). The other, adenocarcinoma, usually develops from the glandular cells that line the cervical canal (the endocervix). The stage of the cancer is defined by its size and by the extent of spread beyond the cervix.\n\nThe most common symptoms of cervical cancer are abnormal vaginal bleeding or discharge and discomfort during intercourse.\n\nCancer of the cervix can be treated with surgery, radiotherapy, chemotherapy or a combination of these treatments. Surgery is often the main treatment for cancer of the cervix in its early stages (where cancer is found only in the cervix). Chemotherapy is occasionally used before surgery, shrinking the cancer to make the operation simpler. However, it is mainly given in combination with radiotherapy, either as a primary therapy or after surgery.\n\nBrachytherapy can be given in low, medium or high dose rates. Low dose rate brachytherapy delivers radiation slowly. In order to administer a radiation dose that will eliminate the cancer, applicators need to be in place in the vagina for 2 to 3 days.\n\n# Outline of the procedure\n\nHigh dose rate (HDR) brachytherapy was developed to reduce the radiation hazard to staff, and to reduce the length of inpatient treatment, with a requirement for isolation of the patient. HDR brachytherapy may be used for palliation of advanced disease, but this guidance refers only to HDR brachytherapy used with curative intent.\n\nApplicators are put in place in the cervix and connected to an afterloading machine which delivers radiation at a high dose rate, typically for a few minutes. The treatment is often repeated several times, a few days apart, on an outpatient basis. This procedure gives a high dose of radiation to the cervix and the adjacent area, but a low dose to tissues and organs more than a few centimetres away. Practically all HDR brachytherapy is given in conjunction with external-beam radiation therapy.\n\n# Efficacy\n\nIn two randomised controlled trials (RCTs) that compared patients treated with HDR and those treated with low dose rate (LDR) brachytherapy, the overall survival (across all stages of disease) with HDR was 68% and 54% at 3 and 5 years follow-up, respectively, compared with 71% and 55% after LDR brachytherapy. These differences were not significant.\n\nIn an RCT, the overall 5-year survival (across all stages) in 31 patients who had received HDR brachytherapy was 61%, compared with 63% in 29 patients who had received medium dose rate (MDR) treatment. In the same study, local disease-free survival was achieved in 67% of patients who had received HDR brachytherapy compared with 78% in the MDR-treated patients.\n\nDistant metastases occurred in 6% (15/236), 19% (372/1992) and 22% (43/200 and 25/112) of HDR-treated patients in RCTs and a case series. Where the outcome was reported, local recurrence occurred in 6% (7/112), 21% (415/1992) and 22% (51/236) of HDR-treated patients, with follow-up ranging from 3 to 10 years. For more details, refer to the Sources of evidence section.\n\nSome of the Specialist Advisors stated that HDR brachytherapy had equivalent efficacy to LDR brachytherapy.\n\n# Safety\n\nIn a large case series of 1992 patients, with a median 8-year follow-up, the overall bowel and bladder complication rate was 35%. Radiation Therapy Oncology Group grade 3 or 4 complications occurred in 7% of patients. In an RCT that compared HDR and MDR brachytherapy, the grade 2 complication rate among HDR-treated patients was 13% (4/31). In the MDR arm, there were grade 2 complications in 3% (1/29) of patients.\n\nWhere reported separately, rectal complications (all grades) affected 4% to 20% (22/112) of patients, and bladder complications affected 4% (8/200) of patients. Serious complications such as bowel obstruction, severe rectal bleeding and stenosis, which required subsequent surgery, occurred in 2% and 6% (11/200) of patients in two case series. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors reported that complications include diarrhoea, bleeding, colitis and cystitis, and also fistulae requiring surgery. They noted the possibility of long-term problems affecting the bowel, bladder and rectum.\n\n# Other comments\n\nConsultees highlighted that this procedure can be very painful.\n\nAndrew DillonChief ExecutiveMarch 2006', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of high dose rate (HDR) brachytherapy for carcinoma of the cervix', August 2005.\n\n# Information for the public\n\nNICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg160
fb94ce07b86d534afb28675b6f4ebfe58bcc3952	nice	Percutaneous endoscopic colostomy	Percutaneous endoscopic colostomy # Guidance Current evidence on the safety and efficacy of percutaneous endoscopic colostomy (PEC) appears adequate to support the use of this procedure in elderly and frail patients with recurrent sigmoid volvulus and colonic motility problems provided that the normal arrangements are in place for audit and clinical governance. Evidence on the use of PEC in children is limited. The care of children with chronic refractory constipation is complex and further evidence on the efficacy of the procedure and its place in the management of children would be useful. Patient selection in children is particularly important and should involve a multidisciplinary team that includes a paediatric gastroenterologist and colorectal surgeon. This procedure should be performed in specialist paediatric units. Patients and/or their parents should be fully informed about the potential risk of peritonitis. They should be provided with clear written information. In addition, use of the Institute's information for the public is recommended.# The procedure # Indications Percutaneous endoscopic colostomy is indicated primarily for recurrent sigmoid volvulus (twisting of the section of the bowel above the rectum) and colonic pseudo-obstruction. It may also be indicated in the treatment of children with constipation that is refractory to all medical treatments. Sigmoid volvulus is more common in people older than 60 years, and in those with Hirschsprung's disease. It is also particularly common in people with chronic constipation. Sigmoid volvulus can be life threatening and must be promptly diagnosed and treated. Emergency treatment usually involves untwisting the bowel using a flatus tube or colonoscope. Subsequently, surgery may be considered to prevent recurrence, especially in patients who have suffered repeated episodes of sigmoid volvulus. Existing surgical techniques include sigmoidopexy, sigmoidoplasty, sigmoid colectomy and primary anastomosis. These treatment options have varying success rates and open resection may be contraindicated for elderly and frail patients or severely immunocompromised patients. Percutaneous endoscopic colostomy offers an alternative treatment for patients who have tried conventional treatment options without success or those who are unfit for surgery. # Outline of the procedure Percutaneous endoscopic colostomy has evolved from percutaneous endoscopic gastrostomy (PEG). Percutaneous endoscopic colostomy (PEC) is a minimally invasive procedure. PEC tubing is placed in position using a colonoscope, which is inserted into the left colon through the rectum. A wire is passed through a small skin incision and pulled back through the anal canal via the colonoscope. The PEC tube is tied to the wire, pulled back through the bowel and abdominal wall, and secured against the abdominal wall. The colonoscope is re-inserted to check the final position of the PEC tube. The tube is then attached to a drainage bag, which is usually flushed twice a day. Prophylactic antibiotics are administered for a few days. # Efficacy The published evidence on this procedure is limited. The largest published case series includes 15 children with refractory constipation, of whom 14 underwent the procedure and 6 were followed up for 12 months. All children evaluated at 12 months were socially clean (mostly clean with occasional accidents, or no soiling) and two children were able to have the tube removed. In another case series of 14 elderly patients with recurrent sigmoid volvulus, 5 patients whose tubes had been left in situ remained recurrence free at a mean follow-up of 12.6 months. For more details, refer to the Sources of evidence section. The Specialist Advisors stated that outcomes seemed to be better in patients with sigmoid volvulus than in those with incontinence or constipation. # Safety The most common complications reported were granuloma formation (6/15 and 4/6 in two case series) and infection (3/15 and 2/6). Other reported complications included pain associated with the administration of an enema (1/15), colonic leakage (5/6) and tube erosion (1/6). Preliminary unpublished data from a multicentre UK audit reported a 12% infection rate (13/105 patients) following the procedure. Two deaths attributed to late tube dislodgement were reported in patients treated for recurrent sigmoid volvulus. For more details, refer to the Sources of evidence section. The Specialist Advisors listed the potential complications as infection, perforation leading to peritonitis, and bleeding. # Other comments It was noted that there was an additional death resulting from peritonitis following a PEC procedure. Andrew DillonChief ExecutiveMarch 2006# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of percutaneous endoscopic colostomy', August 2005. # Information for the public NICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of percutaneous endoscopic colostomy (PEC) appears adequate to support the use of this procedure in elderly and frail patients with recurrent sigmoid volvulus and colonic motility problems provided that the normal arrangements are in place for audit and clinical governance.\n\nEvidence on the use of PEC in children is limited. The care of children with chronic refractory constipation is complex and further evidence on the efficacy of the procedure and its place in the management of children would be useful. Patient selection in children is particularly important and should involve a multidisciplinary team that includes a paediatric gastroenterologist and colorectal surgeon. This procedure should be performed in specialist paediatric units.\n\nPatients and/or their parents should be fully informed about the potential risk of peritonitis. They should be provided with clear written information. In addition, use of the Institute's information for the public is recommended.", 'The procedure': "# Indications\n\nPercutaneous endoscopic colostomy is indicated primarily for recurrent sigmoid volvulus (twisting of the section of the bowel above the rectum) and colonic pseudo-obstruction. It may also be indicated in the treatment of children with constipation that is refractory to all medical treatments.\n\nSigmoid volvulus is more common in people older than 60 years, and in those with Hirschsprung's disease. It is also particularly common in people with chronic constipation. Sigmoid volvulus can be life threatening and must be promptly diagnosed and treated. Emergency treatment usually involves untwisting the bowel using a flatus tube or colonoscope. Subsequently, surgery may be considered to prevent recurrence, especially in patients who have suffered repeated episodes of sigmoid volvulus.\n\nExisting surgical techniques include sigmoidopexy, sigmoidoplasty, sigmoid colectomy and primary anastomosis. These treatment options have varying success rates and open resection may be contraindicated for elderly and frail patients or severely immunocompromised patients.\n\nPercutaneous endoscopic colostomy offers an alternative treatment for patients who have tried conventional treatment options without success or those who are unfit for surgery.\n\n# Outline of the procedure\n\nPercutaneous endoscopic colostomy has evolved from percutaneous endoscopic gastrostomy (PEG).\n\nPercutaneous endoscopic colostomy (PEC) is a minimally invasive procedure. PEC tubing is placed in position using a colonoscope, which is inserted into the left colon through the rectum. A wire is passed through a small skin incision and pulled back through the anal canal via the colonoscope. The PEC tube is tied to the wire, pulled back through the bowel and abdominal wall, and secured against the abdominal wall. The colonoscope is re-inserted to check the final position of the PEC tube. The tube is then attached to a drainage bag, which is usually flushed twice a day. Prophylactic antibiotics are administered for a few days.\n\n# Efficacy\n\nThe published evidence on this procedure is limited. The largest published case series includes 15 children with refractory constipation, of whom 14 underwent the procedure and 6 were followed up for 12 months. All children evaluated at 12 months were socially clean (mostly clean with occasional accidents, or no soiling) and two children were able to have the tube removed.\n\nIn another case series of 14 elderly patients with recurrent sigmoid volvulus, 5 patients whose tubes had been left in situ remained recurrence free at a mean follow-up of 12.6 months. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors stated that outcomes seemed to be better in patients with sigmoid volvulus than in those with incontinence or constipation.\n\n# Safety\n\nThe most common complications reported were granuloma formation (6/15 and 4/6 in two case series) and infection (3/15 and 2/6). Other reported complications included pain associated with the administration of an enema (1/15), colonic leakage (5/6) and tube erosion (1/6). Preliminary unpublished data from a multicentre UK audit reported a 12% infection rate (13/105 patients) following the procedure. Two deaths attributed to late tube dislodgement were reported in patients treated for recurrent sigmoid volvulus. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors listed the potential complications as infection, perforation leading to peritonitis, and bleeding.\n\n# Other comments\n\nIt was noted that there was an additional death resulting from peritonitis following a PEC procedure.\n\nAndrew DillonChief ExecutiveMarch 2006", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of percutaneous endoscopic colostomy', August 2005.\n\n# Information for the public\n\nNICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg161
cc1df9fa2b5a3ccc49c35461b3edfdbf06da880b	nice	Stent-graft placement in abdominal aortic aneurysm	Stent-graft placement in abdominal aortic aneurysm # Guidance This guidance replaces the previous guidance on stent-graft placement in abdominal aortic aneurysm (Interventional Procedures Guidance no. 10, September 2003). The Interventional Procedures Advisory Committee reconsidered the procedure based on the results of a systematic review commissioned by NICE, following publication of the results of the EndoVascular Aneurysm Repair (EVAR) trials. Current evidence on the efficacy and short-term safety of stent–graft placement in abdominal aortic aneurysm appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Clinicians should ensure that patients fully understand the long-term uncertainties and the potential complications associated with this procedure. In particular, patients should understand: the risks of endovascular leaks; the possibility of secondary intervention; and the need for lifelong follow-up. Patients should be provided with clear written information. In addition, use of the Institute's information for the public is recommended. Patient selection is important, particularly for patients who would normally be considered unfit for surgery. Publication of long-term data would be useful. It is recommended that all patients who have the procedure are entered onto one of the existing registries.# The procedure # Indications Stent–graft placement is used to treat aneurysms of the abdominal aorta. Weakening of the wall of the aorta can lead to widening of the vessel, or aneurysm. Aneurysms may rupture causing internal bleeding which, if untreated, is usually fatal. The standard treatment for abdominal aortic aneurysm is open surgical repair. The aneurysm is opened and a graft is then sewn in above and below the weakened area to allow normal blood flow. # Outline of the procedure Stent–graft placement is a minimally invasive alternative to open repair. The graft is mounted on a stent, which is inserted into the aorta via catheters in the femoral arteries. The stent–graft is deployed under X-ray guidance and positioned across the aneurysm. Additional endovascular or surgical interventions may be necessary to complete the procedure, such as insertion of stents into the iliac arteries, occlusion of selected arteries and femoro-femoral bypass grafts. # Efficacy A systematic review of the published evidence on this procedure was commissioned by the Institute and completed in June 2005. A total of 77 studies were identified for inclusion. This comprised: four randomised controlled trials (RCTs) including the EndoVascular Aneurysm Repair (EVAR) 1 trial comparing stent–graft placement and open surgical repair, and the EVAR 2 trial comparing stent–graft placement in patients considered unfit for surgical repair with standard medical care; 17 non-randomised controlled trials; 22 comparative observational studies; 28 case series and six registry publications. Data from the EVAR 1 trial at a median follow-up of 35 months reported an aneurysm rupture rate of 0.9% (5/543) following endovascular repair, compared with 0.2% (1/539) following open repair. Early aneurysm rupture rates of 0.2% (1/534) and 0.3% (13/3859) were reported in one non-randomised controlled trial and seven case series, respectively. In the EVAR 1 trial, 16% (85/529) of patients required secondary intervention following stent–graft placement, compared with 7% (36/519) of patients following open repair. From the non-randomised controlled studies, secondary intervention rates were 20% following stent–graft placement and 6% following open repair. The EVAR 2 trial reported that at 4 years, 26% of the group who had had stent–graft placement had required at least one additional intervention compared with 4% of the group who had received standard medical care. However, if crossovers are considered a secondary intervention, then the secondary intervention rate in the group that received standard medical care became comparable (approximately 30%). For more details, refer to the Sources of evidence. # Safety From a meta-analysis of data from three RCTs, stent–graft placement was associated with a 30-day mortality rate of 2% (12/759 patients) compared with 5% (33/709 patients) for open repair. In patients considered unfit for surgery, the 30-day mortality following stent–graft placement was 9% (13/150 patients). During more prolonged follow-up to 4 years, the EVAR 1 trial reported no significant difference between the all-cause mortality rate in the group that had had stent–graft placement and the group that had had open repair. The most common adverse event following stent–graft placement was endoleak originating from retrograde collateral flow into the aneurysm sac via aortic branches (type II). This occurred in 19% of patients at 1 year. Recent developments have led to a lower incidence of procedural and post-procedural complications. The incidence of pulmonary complications and haemorrhagic events was significantly lower in the stent–graft placement group than in the open repair group. Technical complications included stent migration, which happened in 1% of patients within the first year, and stent wire fracture, which happened in 3% of patients within the first year. For more details, refer to the Sources of evidence. # Other comments It was noted that these procedures are rapidly evolving. The follow-up phase of the EVAR trials continues, and long-term results are expected to be published in 2010. Andrew DillonChief ExecutiveMarch 2006# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'A systematic review update of the recent evidence for the safety and efficacy of elective endovascular repair in the management of infrarenal abdominal aortic aneurysms', June 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Other NICE recommendations on endovascular stent-grafts In February 2009 NICE published guidance on abdominal aortic aneurysm – endovascular stent-grafts that complements this guidance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It updates and replaces NICE interventional procedure guidance 10. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "This guidance replaces the previous guidance on stent-graft placement in abdominal aortic aneurysm (Interventional Procedures Guidance no. 10, September 2003). The Interventional Procedures Advisory Committee reconsidered the procedure based on the results of a systematic review commissioned by NICE, following publication of the results of the EndoVascular Aneurysm Repair (EVAR) trials.\n\nCurrent evidence on the efficacy and short-term safety of stent–graft placement in abdominal aortic aneurysm appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians should ensure that patients fully understand the long-term uncertainties and the potential complications associated with this procedure. In particular, patients should understand: the risks of endovascular leaks; the possibility of secondary intervention; and the need for lifelong follow-up. Patients should be provided with clear written information. In addition, use of the Institute's information for the public is recommended.\n\nPatient selection is important, particularly for patients who would normally be considered unfit for surgery.\n\nPublication of long-term data would be useful. It is recommended that all patients who have the procedure are entered onto one of the existing registries.", 'The procedure': '# Indications\n\nStent–graft placement is used to treat aneurysms of the abdominal aorta. Weakening of the wall of the aorta can lead to widening of the vessel, or aneurysm. Aneurysms may rupture causing internal bleeding which, if untreated, is usually fatal.\n\nThe standard treatment for abdominal aortic aneurysm is open surgical repair. The aneurysm is opened and a graft is then sewn in above and below the weakened area to allow normal blood flow.\n\n# Outline of the procedure\n\nStent–graft placement is a minimally invasive alternative to open repair. The graft is mounted on a stent, which is inserted into the aorta via catheters in the femoral arteries. The stent–graft is deployed under X-ray guidance and positioned across the aneurysm. Additional endovascular or surgical interventions may be necessary to complete the procedure, such as insertion of stents into the iliac arteries, occlusion of selected arteries and femoro-femoral bypass grafts.\n\n# Efficacy\n\nA systematic review of the published evidence on this procedure was commissioned by the Institute and completed in June 2005. A total of 77 studies were identified for inclusion. This comprised: four randomised controlled trials (RCTs) including the EndoVascular Aneurysm Repair (EVAR) 1 trial comparing stent–graft placement and open surgical repair, and the EVAR 2 trial comparing stent–graft placement in patients considered unfit for surgical repair with standard medical care; 17 non-randomised controlled trials; 22 comparative observational studies; 28 case series and six registry publications.\n\nData from the EVAR 1 trial at a median follow-up of 35 months reported an aneurysm rupture rate of 0.9% (5/543) following endovascular repair, compared with 0.2% (1/539) following open repair. Early aneurysm rupture rates of 0.2% (1/534) and 0.3% (13/3859) were reported in one non-randomised controlled trial and seven case series, respectively.\n\nIn the EVAR 1 trial, 16% (85/529) of patients required secondary intervention following stent–graft placement, compared with 7% (36/519) of patients following open repair. From the non-randomised controlled studies, secondary intervention rates were 20% following stent–graft placement and 6% following open repair.\n\nThe EVAR 2 trial reported that at 4 years, 26% of the group who had had stent–graft placement had required at least one additional intervention compared with 4% of the group who had received standard medical care. However, if crossovers are considered a secondary intervention, then the secondary intervention rate in the group that received standard medical care became comparable (approximately 30%). For more details, refer to the Sources of evidence.\n\n# Safety\n\nFrom a meta-analysis of data from three RCTs, stent–graft placement was associated with a 30-day mortality rate of 2% (12/759 patients) compared with 5% (33/709 patients) for open repair. In patients considered unfit for surgery, the 30-day mortality following stent–graft placement was 9% (13/150 patients).\n\nDuring more prolonged follow-up to 4 years, the EVAR 1 trial reported no significant difference between the all-cause mortality rate in the group that had had stent–graft placement and the group that had had open repair.\n\nThe most common adverse event following stent–graft placement was endoleak originating from retrograde collateral flow into the aneurysm sac via aortic branches (type II). This occurred in 19% of patients at 1 year. Recent developments have led to a lower incidence of procedural and post-procedural complications. The incidence of pulmonary complications and haemorrhagic events was significantly lower in the stent–graft placement group than in the open repair group.\n\nTechnical complications included stent migration, which happened in 1% of patients within the first year, and stent wire fracture, which happened in 3% of patients within the first year. For more details, refer to the Sources of evidence.\n\n# Other comments\n\nIt was noted that these procedures are rapidly evolving.\n\nThe follow-up phase of the EVAR trials continues, and long-term results are expected to be published in 2010.\n\nAndrew DillonChief ExecutiveMarch 2006', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'A systematic review update of the recent evidence for the safety and efficacy of elective endovascular repair in the management of infrarenal abdominal aortic aneurysms', June 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Other NICE recommendations on endovascular stent-grafts': 'In February 2009 NICE published guidance on abdominal aortic aneurysm – endovascular stent-grafts that complements this guidance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt updates and replaces NICE interventional procedure guidance 10.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg163
aa5123f74d28327383e42d484fba7d4fa16597a1	nice	Photorefractive (laser) surgery for the correction of refractive errors	Photorefractive (laser) surgery for the correction of refractive errors # Guidance This document replaces previous guidance on laser in situ keratomileusis (LASIK) (NICE Interventional Procedure Guidance no. 102). Current evidence suggests that photorefractive (laser) surgery for the correction of refractive errors is safe and efficacious for use in appropriately selected patients. Clinicians undertaking photorefractive (laser) surgery for the correction of refractive errors should ensure that patients understand the benefits and potential risks of the procedure. Risks include failure to achieve the expected improvement in unaided vision, development of new visual disturbances, corneal infection and flap complications. These risks should be weighed against those of wearing spectacles or contact lenses. Clinicians should audit and review clinical outcomes of all patients who have photorefractive (laser) surgery for the correction of refractive errors. Further research will be useful and clinicians are encouraged to collect longer-term follow-up data. Clinicians should have adequate training before performing these procedures. The Royal College of Ophthalmologists has produced standards for laser refractive surgery.# The procedure # Indications Photorefractive (laser) surgery is used to treat refractive errors such as myopia, astigmatism and hyperopia. Refractive errors are usually corrected by wearing spectacles or contact lenses. Surgical treatments have been developed to improve refraction by re-shaping the cornea. # Outline of the procedure In photorefractive surgery, corneal re-shaping is achieved using excimer laser ablation. Excimer laser techniques include photorefractive keratectomy (PRK), laser epithelial keratomileusis (LASEK) and laser in situ keratomileusis (LASIK). PRK involves the removal of the corneal epithelium by surgical dissection and excimer laser ablation of a calculated amount of the stromal bed of the cornea. LASEK is a modification of PRK; dilute alcohol is used to loosen the corneal epithelium before it is lifted from the treatment zone as a hinged sheet, and then replaced at the end of the procedure. In LASIK, a flap is created with a microkeratome; this is lifted before laser ablation and then repositioned. # Efficacy A systematic review of the published evidence on these procedures was commissioned by the Institute. In seven randomised controlled trials (RCTs) included in the review, there were no significant differences between the three procedures in the proportion of eyes treated for myopia or myopic astigmatism achieving the predicted refractive outcome. Data from more than 2000 eyes treated with PRK for myopia showed that a median of 69% of eyes had achieved within 0.5 D of their intended correction, and that 89% had achieved within 1.0 D. Data from case series of more than 1800 eyes undergoing LASEK for myopia or astigmatism showed that a median of 75% of eyes were within 0.5 D and a median of 92% of eyes were within 1.0 D of their intended correction at 3–6 months follow-up. Data from eyes treated with LASIK for myopia or astigmatism showed that 77% (7309/9542) were within 0.5 D and 91% (8109/8885) were within 1.0 D of their intended correction at 3–12 months. One RCT found LASEK to be significantly more accurate than PRK for eyes with hyperopia. Final uncorrected visual acuity achieved was similar for all three techniques. For more details, refer to the Sources of evidence. # Safety In eyes treated for myopia, loss of two lines of best spectacle-corrected visual acuity was seen in a median of 0.5% (0–20.5%) of eyes treated with PRK, 0% (0–8.2%) of eyes treated with LASEK and 0.6% (0–3%) of eyes treated with LASIK. Patients with high myopia were more likely to lose two or more lines of best spectacle-corrected visual acuity than those with moderate to low myopia. Flap complications may occur during LASIK and LASEK, requiring conversion to PRK or postponement of ablation (with LASIK), and occasionally there may be loss of best spectacle-corrected visual acuity. Epithelial in-growth was reported in LASIK in a median of 1.3% (0.0–4.4%) of eyes. Ectasia, a condition that can result from corneal thinning, is a serious complication related to refractive surgery that can lead to loss of vision. Data from the review estimated the risk of ectasia following LASIK as a median of 0.2% (range 0 to 0.87%; overall rate of 40/10,806 eyes). However, many of the affected eyes may have been selected inappropriately for LASIK treatment, and with appropriate patient selection the rate might have been lower. Rates of ectasia were not reported following PRK, and very little information was reported about LASEK, with no cases of ectasia described in one case series of 171 eyes. Microbial keratitis was only reported in LASIK studies and occurred in 0–0.16% of eyes. This incidence was similar to, or lower than, that reported for contact lens wearers. Other patient-reported problems included visual difficulty in low light conditions, corneal haze, light halos and problems with glare. Significant corneal haze was reported following all three procedures (in 0–31% of eyes treated with PRK, 0–25% with LASEK and 0–2% with LASIK). Glare and night vision difficulties were less common after LASIK. For more details, refer to the Sources of evidence. # Other comments These procedures can make it more difficult to measure accurately the intraocular pressure used to detect glaucoma, and the intraocular lens power required for cataract surgery. Techniques are available to address these difficulties, provided it is known that photorefractive surgery has previously been done. It was recognised that this is a rapidly evolving procedure and that new techniques are emerging. The current difficulties for patients in identifying properly trained practitioners for this procedure were noted. A working group of the Royal College of Opthalmologists is currently devising a set of defined learning outcomes and assessments for all those wishing to undertake laser refractive surgery. Andrew DillonChief ExecutiveMarch 2006# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'A systematic review of the safety and efficacy of elective photorefractive surgery for the correction of refractive error', April 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It updates and replaces NICE interventional procedure guidance 102. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'This document replaces previous guidance on laser in situ keratomileusis (LASIK) (NICE Interventional Procedure Guidance no. 102).\n\nCurrent evidence suggests that photorefractive (laser) surgery for the correction of refractive errors is safe and efficacious for use in appropriately selected patients.\n\nClinicians undertaking photorefractive (laser) surgery for the correction of refractive errors should ensure that patients understand the benefits and potential risks of the procedure. Risks include failure to achieve the expected improvement in unaided vision, development of new visual disturbances, corneal infection and flap complications. These risks should be weighed against those of wearing spectacles or contact lenses.\n\nClinicians should audit and review clinical outcomes of all patients who have photorefractive (laser) surgery for the correction of refractive errors. Further research will be useful and clinicians are encouraged to collect longer-term follow-up data.\n\nClinicians should have adequate training before performing these procedures. The Royal College of Ophthalmologists has produced standards for laser refractive surgery.', 'The procedure': '# Indications\n\nPhotorefractive (laser) surgery is used to treat refractive errors such as myopia, astigmatism and hyperopia.\n\nRefractive errors are usually corrected by wearing spectacles or contact lenses. Surgical treatments have been developed to improve refraction by re-shaping the cornea.\n\n# Outline of the procedure\n\nIn photorefractive surgery, corneal re-shaping is achieved using excimer laser ablation. Excimer laser techniques include photorefractive keratectomy (PRK), laser epithelial keratomileusis (LASEK) and laser in situ keratomileusis (LASIK).\n\nPRK involves the removal of the corneal epithelium by surgical dissection and excimer laser ablation of a calculated amount of the stromal bed of the cornea. LASEK is a modification of PRK; dilute alcohol is used to loosen the corneal epithelium before it is lifted from the treatment zone as a hinged sheet, and then replaced at the end of the procedure. In LASIK, a flap is created with a microkeratome; this is lifted before laser ablation and then repositioned.\n\n# Efficacy\n\nA systematic review of the published evidence on these procedures was commissioned by the Institute.\n\nIn seven randomised controlled trials (RCTs) included in the review, there were no significant differences between the three procedures in the proportion of eyes treated for myopia or myopic astigmatism achieving the predicted refractive outcome. Data from more than 2000 eyes treated with PRK for myopia showed that a median of 69% of eyes had achieved within 0.5 D of their intended correction, and that 89% had achieved within 1.0 D. Data from case series of more than 1800 eyes undergoing LASEK for myopia or astigmatism showed that a median of 75% of eyes were within 0.5 D and a median of 92% of eyes were within 1.0 D of their intended correction at 3–6 months follow-up. Data from eyes treated with LASIK for myopia or astigmatism showed that 77% (7309/9542) were within 0.5 D and 91% (8109/8885) were within 1.0 D of their intended correction at 3–12 months. One RCT found LASEK to be significantly more accurate than PRK for eyes with hyperopia.\n\nFinal uncorrected visual acuity achieved was similar for all three techniques. For more details, refer to the Sources of evidence.\n\n# Safety\n\nIn eyes treated for myopia, loss of two lines of best spectacle-corrected visual acuity was seen in a median of 0.5% (0–20.5%) of eyes treated with PRK, 0% (0–8.2%) of eyes treated with LASEK and 0.6% (0–3%) of eyes treated with LASIK. Patients with high myopia were more likely to lose two or more lines of best spectacle-corrected visual acuity than those with moderate to low myopia.\n\nFlap complications may occur during LASIK and LASEK, requiring conversion to PRK or postponement of ablation (with LASIK), and occasionally there may be loss of best spectacle-corrected visual acuity. Epithelial in-growth was reported in LASIK in a median of 1.3% (0.0–4.4%) of eyes.\n\nEctasia, a condition that can result from corneal thinning, is a serious complication related to refractive surgery that can lead to loss of vision. Data from the review estimated the risk of ectasia following LASIK as a median of 0.2% (range 0 to 0.87%; overall rate of 40/10,806 eyes). However, many of the affected eyes may have been selected inappropriately for LASIK treatment, and with appropriate patient selection the rate might have been lower. Rates of ectasia were not reported following PRK, and very little information was reported about LASEK, with no cases of ectasia described in one case series of 171 eyes.\n\nMicrobial keratitis was only reported in LASIK studies and occurred in 0–0.16% of eyes. This incidence was similar to, or lower than, that reported for contact lens wearers.\n\nOther patient-reported problems included visual difficulty in low light conditions, corneal haze, light halos and problems with glare. Significant corneal haze was reported following all three procedures (in 0–31% of eyes treated with PRK, 0–25% with LASEK and 0–2% with LASIK). Glare and night vision difficulties were less common after LASIK. For more details, refer to the Sources of evidence.\n\n# Other comments\n\nThese procedures can make it more difficult to measure accurately the intraocular pressure used to detect glaucoma, and the intraocular lens power required for cataract surgery. Techniques are available to address these difficulties, provided it is known that photorefractive surgery has previously been done.\n\nIt was recognised that this is a rapidly evolving procedure and that new techniques are emerging.\n\nThe current difficulties for patients in identifying properly trained practitioners for this procedure were noted. A working group of the Royal College of Opthalmologists is currently devising a set of defined learning outcomes and assessments for all those wishing to undertake laser refractive surgery.\n\nAndrew DillonChief ExecutiveMarch 2006', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'A systematic review of the safety and efficacy of elective photorefractive surgery for the correction of refractive error', April 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt updates and replaces NICE interventional procedure guidance 102.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg164
640268ff638a9c84a082842aa6a28461b1495cb0	nice	Adefovir dipivoxil and peginterferon alfa-2a for the treatment of chronic hepatitis B	Adefovir dipivoxil and peginterferon alfa-2a for the treatment of chronic hepatitis B Evidence-based recommendations on adefovir dipivoxil (Hepsera) and peginterferon alfa-2a (Pegasys) for treating chronic hepatitis B in adults. # Guidance This guidance was partially updated by NICE clinical guideline 165 in June 2013. See About this guidance for more information. This guidance does not apply to people with chronic hepatitis B known to be co-infected with hepatitis C, hepatitis D or HIV. Peginterferon alfa-2a is recommended as an option for the initial treatment of adults with chronic hepatitis B (HBeAg-positive or HBeAg-negative), within its licensed indications. This recommendation has been replaced by recommendation 1.5.13 in NICE clinical guideline 165. This recommendation has been replaced by recommendation 1.5.14 in NICE clinical guideline 165. This recommendation has been replaced by recommendation 1.5.15 in NICE clinical guideline 165.# Clinical need and practice Chronic hepatitis B is defined as viraemia and hepatic inflammation that persists for more than 6 months after acute infection with hepatitis B virus. Hepatitis B virus is transmitted by sexual contact, through the use of infected blood and blood products, by reuse of contaminated needles and syringes, by vertical transmission from mother to child during, or soon after, birth, and by horizontal transmission among children. The risk of chronic infection with hepatitis B virus depends on the nature of the immune response to the initial infection. This varies according to the age at which the infection is acquired. Almost 100% of neonates, and about 50% of young children, develop chronic hepatitis B if infected with hepatitis B virus. In contrast, only about 2–10% of people who are infected as adults go on to develop chronic hepatitis B. The Department of Health estimates that about 180,000 people in the UK have chronic hepatitis B. There are about 7700 new cases of chronic hepatitis B each year. Of these, around 300 people were infected within the UK; the remainder (mainly immigrants to the UK) were infected abroad, generally in areas of high prevalence where the virus is frequently transmitted from mother to child. People with active chronic hepatitis B are at increased risk of liver cirrhosis (scarring of the liver tissue that may progress to liver failure) and primary liver cancer (hepatocellular carcinoma). The diagnosis of chronic hepatitis B is based on the presence of well-characterised serological markers in the blood. Hepatitis B viral DNA (HBV DNA) is present in both acute and chronic hepatitis B. Hepatitis B surface antigen (HBsAg) is a viral protein detectable in the blood in both acute and chronic infection. Chronic hepatitis B is defined as persistence of HBsAg for 6 months or more after acute infection. Hepatitis B 'e' antigen (HBeAg) is an indicator of viral replication, although some variant forms of the virus do not express HBeAg (see section 2.5.5 below). Active infection can be described as HBeAg-positive or HBeAg-negative according to whether HBeAg is secreted. The natural history of chronic hepatitis B can be divided into phases, each of which may last many years. Immunotolerant phase.People who are affected at birth or in early childhood initially enter an 'immunotolerant' phase during which the immune system does not actively fight the virus. The virus replicates rapidly during this phase, but the person usually has no symptoms. The person is highly infectious, and may infect other members of the family and community. This phase can last for many years before progressing to active disease. Incubation. The incubation period for hepatitis B infection ranges from 40–160 days, with an average of 60–90 days. Active chronic hepatitis B.The first stage of active disease involves a period of increasing inflammatory hepatic necrosis as the immune system begins to fight the virus. This stage of the disease is characterised by elevated levels of viral DNA in the blood, persistently raised levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and evidence of hepatic necrosis and inflammation on biopsy. The liver damage caused by infection and inflammation may eventually lead to cirrhosis of the liver. Progression to cirrhosis occurs at an annual rate of 2–5.5%, with a cumulative 5-year rate of progression of 8–20%. HBeAg seroconversion In people infected with an HBeAg-positive form of the virus, the next stage of the infection occurs when inflammation becomes sufficiently intense to cause lysis of infected hepatocytes. This produces a 'flare' of the disease with symptoms resembling acute hepatitis B, and leads to the development of antibodies against the 'e' antigen. This is referred to as 'HBeAg seroconversion'. The seroconverted disease state is associated with good quality of life and a relatively low risk of disease progression. It is referred to as the 'inactive HBsAg carrier state' because patients continue to express hepatitis B surface antigen (HBsAg). The spontaneous seroconversion rate is 5–10% per year, although this varies among populations. Once seroconversion has taken place, most people remain in the inactive HBsAg carrier state. However, increasing viraemia and recurrent hepatitis after seroconversion indicate the emergence of the HBeAg-negative strain of the virus. HBeAg-negative chronic hepatitis B In recent years a form of the virus that does not cause infected cells to secrete HBeAg has been discovered (sometimes called the 'precore mutant' strain). People can be infected with the so-called HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in people initially infected with the HBeAg-positive form of the virus. The prevalence of HBeAg-negative hepatitis varies geographically; it is more common in Asia and the Mediterranean region than in Northern Europe. Infection with HBeAg-negative chronic hepatitis B is associated with a fluctuating course and a poor prognosis. Active disease is associated with either persistent elevation of ALT or an erratic pattern of ALT changes with flare-ups resembling acute hepatitis B that can be severe or even fatal. Few patients with HBeAg-negative chronic hepatitis B achieve a lasting remission. Progression to cirrhosis of the liver has been estimated to occur in 8-10% of people with HBeAg-negative chronic hepatitis B each year. HBsAg seroconversion.The development of antibodies against HBsAg, with clearance of HBsAg, occurs spontaneously in about 0.5–2% of people with chronic hepatitis B each year in western countries. In countries where hepatitis B is endemic, the rate is much lower – between 0.05 and 0.08% per year. Clearance of HBsAg is most likely to occur in the year following HBeAg seroconversion. It signifies resolution of the chronic infection. Variants of hepatitis B (known as 'occult hepatitis B') that are not associated with detectable HBsAg by current immunoassays have been recognised. The aim of treatment is to prevent progression to cirrhosis or hepatocellular carcinoma. Treatment may be given as a finite course (circumscribed therapy) – with the intention of allowing the immune system to respond and control the infection without the need for further drug treatment – or as long-term viral suppressive therapy. Long-term therapy is needed if short-term therapy is unsuccessful. The first drugs to be licensed for the treatment of chronic hepatitis B were alfa interferons. Interferons are natural proteins that activate the immune system in response to viral infection. Three recombinant interferon products have UK marketing authorisation for the treatment of chronic hepatitis B: IntronA (interferon alfa-2b, Schering-Plough), Roferon-A (interferon alfa-2a, Roche) and Viraferon (interferon alfa-2b, Schering-Plough). Interferon alfa-2a is usually given at a dose of 2.5–5 million units per square metre of body surface area by subcutaneous injection three times a week for 4–6 months. Interferon alfa-2b is given at a dose of 5–10 million units three times a week for 4–6 months. The side effects of interferons can be severe and this means that they are not suitable for long-term treatment in chronic hepatitis B. Interferons are contraindicated in decompensated liver disease. There are no data on long-term maintenance therapy with an alfa interferon and the treatment is not licensed for this. Lamivudine (Zeffix, GlaxoSmithKline) is a nucleoside reverse transcriptase inhibitor antiviral drug. The dose in adults is 100 mg per day. It can be given both as a circumscribed course of treatment or as long-term viral suppressive therapy. In HBeAg-positive chronic hepatitis B, treatment is usually given for a year with the aim of bringing about HBeAg seroconversion. In HBeAg-negative chronic hepatitis B, a circumscribed course of therapy is less likely to lead to long-term control of the infection, and long-term treatment is often needed. The main problem with long-term antiviral treatment is the emergence of resistance. Resistance to lamivudine occurs in more than 60% of cases after 3 years' treatment.# The technologies # Peginterferon alfa-2a Peginterferon alfa-2a (Pegasys, Roche) has UK marketing authorisation for the treatment of HBeAg-positive or HBeAg-negative chronic hepatitis B in adults with compensated liver disease and evidence of viral replication, increased ALT and histologically verified liver inflammation and/or fibrosis. Peginterferons are formed by attaching strands of polyethylene glycol (PEG) to the interferon molecules. This slows the rate of absorption and excretion of interferon, reducing the fluctuations in serum level that occur with unmodified interferon. Peginterferons are administered once a week, compared with three or more times a week for the unmodified form. Peginterferons have a range of adverse effects similar to those of interferons. These include influenza-like symptoms such as fever, chills, myalgias, arthralgias and headache, which are most likely to occur at the start of treatment and seldom require discontinuation of treatment. Depletion of platelets and white blood cells is common. Other adverse effects include depression, anxiety or emotional lability, which may be severe. Cardiovascular adverse effects include hypertension or hypotension, arrhythmias, oedema, myocardial infarction or stroke. Interferons are contraindicated in chronic hepatitis with decompensated cirrhosis of the liver. For full details of side effects and contraindications, see the 'Summary of product characteristics'. A prefilled syringe containing 180 micrograms of peginterferon alfa-2a costs £132.06 (excluding VAT, 'British national formulary', 50th edition ). The usual dose is 180 micrograms once a week. Costs may vary in different settings because of negotiated procurement discounts. # Adefovir dipivoxil Adefovir is structurally related to the purine base adenine. It is converted intracellularly to the diphosphate, which inhibits the synthesis of hepatitis B virus DNA through competition for the enzyme reverse transcriptase and incorporation into the viral DNA. Adefovir is not well absorbed after oral administration so is given by mouth as the prodrug adefovir dipivoxil. Adefovir dipivoxil (Hepsera, Gilead) has UK marketing authorisation for the treatment of chronic hepatitis B in adults with: compensated liver disease with evidence of active viral replication, persistently elevated serum ALT levels and histological evidence of active liver inflammation and fibrosis decompensated liver disease. The most commonly reported adverse effects for adefovir dipivoxil are gastrointestinal effects including nausea, flatulence, diarrhoea and dyspepsia. Increases in serum creatinine are common but usually mild to moderate. However, cases of renal impairment and acute renal failure have been reported. For full details of side effects and contraindications, see the 'Summary of product characteristics'. A pack containing 30 days' supply of adefovir dipivoxil 10 mg tablets costs £315.00 (excluding VAT, 'BNF'50). Costs may vary in different settings because of negotiated procurement discounts.# Evidence and interpretation The Appraisal Committee (appendix A) considered evidence from a number of sources (appendix B). # Clinical effectiveness ## Peginterferon alfa-2a The Assessment Group found three randomised controlled trials investigating peginterferon alfa-2a in chronic hepatitis B. Two trials were in people with HBeAg-positive chronic hepatitis B, and the third was in people with HBeAg-negative chronic hepatitis B. In HBeAg-positive chronic hepatitis B, the most useful measure of response is HBeAg loss or seroconversion because this signals transition to the inactive carrier state, which is associated with a relatively benign outcome. The rate of HBeAg seroconversion was reported in both studies of peginterferon alfa-2a in HBeAg-positive chronic hepatitis B. One trial was an open-label study in which 194 participants were randomised to one of three doses of peginterferon alfa-2a or interferon alfa-2a. Treatment was for 24 weeks, and was followed by 24-weeks' treatment-free follow-up. The rate of HBeAg seroconversion was higher in the patients treated with peginterferon alfa-2a (32% for all three doses combined) than in patients treated with interferon alfa-2a (25%), but the difference was not statistically significant. ALT levels were also more likely to return to the normal range in the people treated with peginterferon alfa-2a (36% for all three doses combined compared with 25% for interferon alfa-2a). This difference was also not statistically significant. The only statistically significant difference between treatment and control in this trial was for the rate of 'combined response', defined as HBeAg loss, HBV DNA normalisation and ALT normalisation (24% for all three treatment doses combined compared with 12% for control, p = 0.036). The second trial in patients with HBeAg-positive chronic hepatitis B was a comparison of peginterferon alfa-2a with lamivudine, in which 814 people were randomised to peginterferon alfa-2a plus placebo, peginterferon alfa-2a plus lamivudine, or lamivudine alone. The study was partially double blind in that those who were receiving peginterferon alfa-2a were blinded as to whether they were receiving lamivudine. Treatment was for 48 weeks, and was followed by 24-weeks' treatment-free follow-up. The rate of HBeAg seroconversion at week 72 was significantly higher in the patients treated with peginterferon alfa-2a plus placebo (32%) than in those treated with lamivudine alone (19%), p < 0.001. Addition of lamivudine to peginterferon alfa-2a did not improve the HBeAg seroconversion rate over peginterferon alfa-2a alone: the rate in the group that received both lamivudine and peginterferon alfa-2a was 27%. Normalisation of ALT occurred in a higher proportion of the group taking peginterferon alfa-2a than of the group taking lamivudine alone (41% versus 28%, p = 0.002). Again, adding lamivudine to peginterferon alfa-2a did not improve the response rate for this endpoint (ALT normalisation 39%). In HBeAg-negative chronic hepatitis B, a major objective of treatment is suppressing viral replication and preventing progressive liver disease. In clinical trials these outcomes have usually been expressed in terms of decrease in the levels of HBV DNA found in the serum and ALT normalisation. The only study of peginterferon alfa-2a in HBeAg-negative chronic hepatitis B was a three-way comparison of peginterferon alfa-2a plus placebo, peginterferon alfa-2a plus lamivudine, and lamivudine alone (n = 537). Treatment was for 48 weeks and was followed by 24-weeks' treatment-free follow up (72 weeks in total). The study had two predetermined primary measures of efficacy: the normalisation of ALT levels and the suppression of HBV DNA levels to less than 20,000 copies/ml. At week 72, the percentage with normalised ALT was significantly higher in the groups treated with peginterferon alfa-2a than in the lamivudine group (59% with peginterferon alfa-2a monotherapy and 60% for peginterferon alfa-2a plus lamivudine, versus 44% for lamivudine; p = 0.004 and p = 0.003 respectively). For the outcome of virological response (HBV DNA < 20,000 copies/ml) at week 72, the percentage of patients who had a response was significantly higher in the groups treated with peginterferon alfa-2a than in the lamivudine group (43% for peginterferon alfa-2a monotherapy and 44% for peginterferon alfa-2a plus lamivudine, versus 29% for lamivudine; p = 0.007 and p = 0.003 respectively). Treatment-resistance mutations were detected in 32 people (18%) in the lamivudine group and one person (< 1%) in the peginterferon alfa-2a plus lamivudine group (p < 0.001). ## Adefovir dipivoxil The assessment report included five randomised controlled trials of adefovir dipivoxil in chronic hepatitis B. Four of the studies were conducted in people with HBeAg-positive chronic hepatitis B and one was in people with HBeAg-negative chronic hepatitis B. The largest study (n = 515) was a comparison of two doses of adefovir dipivoxil (10 mg and 30 mg) with placebo in people with HBeAg-positive chronic hepatitis B and compensated liver disease. The primary endpoint was histological improvement (defined in terms of a reduction in Knodell necroinflammatory score). Histological improvement was seen in 59% of patients in the adefovir dipivoxil 30 mg group, 53% of patients in the adefovir dipivoxil 10 mg group and 25% of patients in the placebo group (p < 0.001 for both comparisons with placebo). The HBeAg seroconversion rates were 14% for the adefovir dipivoxil 30 mg group, 12% for the adefovir dipivoxil 10 mg group and 6%, for the placebo group. The rates of ALT normalisation were 55% for the 30 mg, 48% for the 10 mg and 16% for the placebo group. Another study (n = 59) investigated adefovir dipivoxil in people with HBeAg-positive chronic hepatitis B, genotypic evidence of lamivudine-resistance, raised ALT and a serum HBV DNA level of at least 106 copies/ml despite ongoing treatment with lamivudine. The patients were randomised to adefovir dipivoxil 10 mg, lamivudine 100 mg, or the addition of adefovir dipivoxil to ongoing lamivudine treatment. The primary endpoint was time-weighted change from baseline in serum HBV DNA level. Reductions in this endpoint were seen in all recipients of adefovir dipivoxil. HBV DNA levels were 'undetectable' (< 1000 copies/ml) in 26% of patients receiving adefovir dipivoxil plus placebo, in 35% of patients receiving adefovir dipivoxil plus lamivudine, and in none of the patients receiving lamivudine plus placebo (p = 0.005). ALT was normalised in 53% of the adefovir dipivoxil plus lamivudine group and 47% of adefovir dipivoxil group, compared with 5% (1/19) of the lamivudine group (p = 0.001 and p = 0.004, respectively) The remaining two studies in HBeAg-positive chronic hepatitis B investigated the combination of adefovir dipivoxil with lamivudine compared with lamivudine alone. One was in treatment-naive patients (n = 112) and the other was in patients with lamivudine resistance (n = 94). In the study in treatment-naive patients (which was still ongoing at the time of this appraisal) there was no advantage in adding adefovir dipivoxil to lamivudine at 1 year in terms of virological, serological or biochemical outcome. However, there was a higher incidence of lamivudine-resistance mutations and viral breakthrough in the group that received lamivudine alone. In the other study of patients with lamivudine resistance, adefovir dipivoxil plus lamivudine was more effective than lamivudine alone in terms of both virological and ALT responses. HBV DNA level fell to 105 copies/ml or less in 85% of those taking adefovir dipivoxil plus lamivudine, compared with 11% of patients taking lamivudine alone (p < 0.001). ALT was normalised in 37% of those taking the combined treatment, compared with 9% of those taking lamivudine (p = 0.003). One study compared adefovir dipivoxil with placebo in people with HBeAg-negative chronic hepatitis B. This was a double-blind study in which 185 people were randomised in a 2:1 ratio to adefovir dipivoxil or placebo for 48 weeks. The primary endpoint was histological improvement defined in terms of a reduction in Knodell necroinflammatory score with no worsening of fibrosis. A total of 167 patients (91%) had assessable pre-treatment and post-treatment liver biopsy specimens. Significantly more patients had histological improvement in the adefovir dipivoxil group than in the placebo group (64% versus 33%, p < 0.001). At week 48, 51% of the adefovir dipivoxil group had undetectable HBV DNA levels (< 400 copies/ml), compared with no one in the placebo group (p < 0.001), and 72% had normalised ALT levels compared with 29% in the placebo group (p < 0.001). Long-term follow-up data have been published recently. After week 48, 123 people who had been assigned to adefovir dipivoxil in the initial study were randomised to continue adefovir dipivoxil at a dose of 10 mg daily or to switch to placebo. Of the 61 patients who had initially been randomised to placebo, 60 switched to treatment with adefovir dipivoxil 10 mg daily. At week 96, HBV DNA was undetectable in 71% of the group continuing with adefovir dipivoxil, compared with 8% of the placebo group. In the group who received adefovir dipivoxil for 48 weeks having previously received placebo for 48 weeks, HBV DNA was undetectable in 76% of patients. The cumulative incidence of resistance to adefovir dipivoxil among all patients was 3% at 96 weeks and 5.9% at 144 weeks. This trial will continue until all patients have completed 5 years' follow-up. ## Evidence from clinical experts The Committee heard from the clinical experts that the decision to treat chronic hepatitis B was determined by the degree of fibrosis and/or necroinflammation on liver biopsy, combined with evidence of active viral replication (HBV DNA levels) and the persistent elevation of serum ALT. Treatment was not necessarily indicated for people with minimal elevation of ALT (1.5–2.0 times the upper limit of normal) and low necroinflammatory scores on liver biopsy. However, these people should be carefully monitored because the disease can change rapidly from a quiescent to an active state. The experts expressed concern about the development of viruses with mutations rendering them resistant to antiviral drugs. Lamivudine resistance develops in a high proportion of patients on monotherapy, and could limit the options for future treatment through cross-resistance to related drugs. The experts noted that a strategy of treating chronic hepatitis B with lamivudine followed by adefovir dipivoxil for those in whom lamivudine-resistance developed reflected current practice. However, the experts noted that there was a subgroup of people with highly replicative disease in whom resistance could develop rapidly; in these people, a strategy of using adefovir dipivoxil in combination with lamivudine might be appropriate. In principle, the use of combination therapies should minimise the risk of developing resistant variants, although long-term follow-up data from studies are lacking. The clinical experts stressed the need for further research on the long-term effectiveness of combination regimens in preventing resistance. # Cost effectiveness The Committee considered evidence from four economic models: one by the Assessment Group, one by each of the two manufacturers involved, and one published analysis by Kanwal and colleagues (which was published after the Assessment Report's deadline for inclusion). The models have similar structures and parameters, and their results are in broad agreement. ## Assessment Group model The Assessment Group model presents analyses for people with HBeAg-positive disease and HBeAg-negative disease separately, and also as a single group, with proportions of people with HBeAg-positive disease and HBeAg-negative disease determined from the parameters of the model. Results are presented for peginterferon alfa-2a (48 weeks' treatment) compared with interferon alfa-2a (24 weeks for HBeAg-positive disease or 48 weeks for HBeAg-negative disease), and for adefovir dipivoxil compared with lamivudine. The incremental cost-effectiveness ratios (ICERs) for these two comparisons in HBeAg-positive and HBeAg-negative groups combined were £6100 and £16,500 per quality-adjusted life year (QALY) respectively. However, this analysis assumes that, if the first therapy does not produce a sustained response, people receive no further treatment other than best supportive care, whereas in practice people may go on to receive treatment with an alternative agent. The Assessment Group therefore produced an analysis that considered more clinically relevant scenarios in which people could receive a sequence of drug treatments as necessary. It is assumed that all patients are first given a course of treatment with either interferon alfa-2a (for 24 or 48 weeks, depending on HBeAg status) or peginterferon alfa-2a for 48 weeks. If HBeAg or HBsAg seroconversion occurs on one of the interferons, the patients are assumed to take no further antiviral medication; if not, they proceed to one of the following sequences of treatment, which form the basis of the comparison: best supportive care, that is, no further antiviral medication lamivudine, then best supportive care on seroconversion or development of resistance adefovir dipivoxil, then best supportive care on seroconversion or development of resistance lamivudine, then adefovir dipivoxil on development of resistance, then best supportive care on seroconversion or development of resistance. The Assessment Group analysis also reports ICERs for the use of lamivudine then best supportive care without first using an interferon, and of adefovir dipivoxil then best supportive care without first using an interferon. It did not report on sequences of both lamivudine and adefovir dipivoxil that were not preceded by an interferon. However, because of the underlying assumptions used in the model, these ICERs can be inferred from the equivalent comparisons for sequences including peginterferon alfa-2a or interferon alfa-2a. Comparing these sets of sequences generated a large number of ICER estimates. However, some of the strategies can be excluded from consideration using the notion of dominance or extended dominance. This means that when strategies A, B and C (in order of increasing cost) are compared, if the ICER for B compared with A is higher than that for C compared with A, and if the benefits of B are less than those of C, then B is excluded. For HBeAg-positive disease, the treatment sequences that are not excluded by extended dominance are as follows: lamivudine then best supportive care (estimated ICER £3500 per QALY compared with best supportive care) interferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care (estimated ICER £9900 per QALY compared with lamivudine then best supportive care) peginterferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care (estimated ICER £18,800 per QALY compared with interferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care) peginterferon alfa-2a then adefovir dipivoxil then lamivudine then best supportive care (estimated ICER £57,000 per QALY compared with peginterferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care). Note that this treatment sequence did not appear in the Assessment Report, but was prepared by the Assessment Group for the Appraisal Committee before its first meeting. For HBeAg-negative disease, the treatment sequences that are not excluded by extended dominance are as follows: peginterferon alfa-2a then best supportive care (estimated ICER £3000 per QALY compared with best supportive care) peginterferon alfa-2a then lamivudine then best supportive care (estimated ICER £4900 per QALY compared with peginterferon alfa-2a then best supportive care) peginterferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care (estimated ICER £18,000 per QALY compared with peginterferon alfa-2a then lamivudine then best supportive care). ## Manufacturer's model (Roche) The model submitted by Roche reports a number of estimated cost effectiveness results, all involving either interferon alfa-2a or peginterferon alfa-2a, for HBeAg-positive and HBeAg-negative disease separately. Nothing is said about later choices for people for whom the interferon has not been clinically effective. The estimated ICERs for people with HBeAg-positive disease are as follows: peginterferon alfa-2a for 24 weeks compared with interferon alfa-2a for 24 weeks (ICER £2700 per QALY) peginterferon alfa-2a for 48 weeks compared with interferon alfa-2a for 24 weeks (ICER £13,900 per QALY) peginterferon alfa-2a for 48 weeks compared with lamivudine for 48 weeks (ICER £5300 per QALY) peginterferon alfa-2a for 48 weeks compared with lamivudine for 208 weeks (ICER £5900 per QALY) peginterferon alfa-2a for 48 weeks compared with adefovir dipivoxil for 48 weeks (ICER £1400 per QALY) peginterferon alfa-2a for 48 weeks compared with adefovir dipivoxil for 208 weeks (dominant, that is, greater benefit at lower cost than adefovir dipivoxil) peginterferon alfa-2a for 48 weeks compared with no treatment (ICER £2800 per QALY). The ICERs for people with HBeAg-negative disease are as follows: peginterferon alfa-2a for 48 weeks compared with lamivudine for 48 weeks (ICER £3200 per QALY) peginterferon alfa-2a for 48 weeks compared with lamivudine for 208 weeks (ICER £1900 per QALY) peginterferon alfa-2a for 48 weeks compared with no treatment (ICER £1500 per QALY). ## Manufacturer's model (Gilead) The model submitted by Gilead presents estimated cost-effectiveness ratios for a number of single treatments and treatment sequences. However, the cost effectiveness of adefovir dipivoxil compared with best supportive care is not reported. The interferons are not considered as treatment options, and the analyses are for a combined population of people with HBeAg-positive and HBeAg-negative disease. The estimated ICERs are as follows: lamivudine then adefovir dipivoxil (when lamivudine resistance emerges) compared with best supportive care – ICER £6700 per QALY lamivudine then adefovir dipivoxil (when lamivudine resistance emerges) compared with lamivudine then best supportive care (when lamivudine resistance emerges) – ICER £9200 per QALY adefovir dipivoxil then lamivudine (when adefovir dipivoxil resistance emerges) compared with best supportive care – ICER £8200 per QALY adefovir dipivoxil then lamivudine (when adefovir dipivoxil resistance emerges) compared with lamivudine then best supportive care (when lamivudine resistance emerges) – ICER £11,400 per QALY adefovir dipivoxil then lamivudine (when adefovir dipivoxil resistance emerges) compared with lamivudine then adefovir dipivoxil (when lamivudine resistance emerges) – ICER £29,400 per QALY. ## Published model The published model (Kanwal and colleagues) evaluated a 'do nothing' strategy (equivalent to best supportive care), interferon alfa, lamivudine, adefovir dipivoxil, and lamivudine then adefovir dipivoxil. For HBeAg-positive disease, the estimated ICERs for the non-dominated strategies are as follows: interferon alfa compared with best supportive care – ICER $2300 (£1300 at an exchange rate of $1.75 per £1) per QALY lamivudine then adefovir dipivoxil, compared with interferon alfa – ICER $16,600 (£9500) per QALY adefovir dipivoxil, compared with lamivudine then adefovir dipivoxil) – ICER $91,000 (£52,000) per QALY. In the analysis for HBeAg-negative disease, lamivudine then adefovir dipivoxil (as salvage therapy after resistance to lamivudine develops) is both cheaper and more effective than all other treatment options. ## Overall results of the models The models show that interferon alfa or peginterferon alfa-2a therapies followed by lamivudine then adefovir dipivoxil, where necessary, appear to be cost effective relative to alternative strategies. In most of the analyses, strategies in which adefovir dipivoxil is used before lamivudine, or without lamivudine, in the sequence are dominated by the alternative strategies. The exceptions are Gilead's estimated ICER of £29,400 per QALY for adefovir dipivoxil then lamivudine, compared with lamivudine then adefovir dipivoxil, and the Assessment Group's estimated ICER of £57,000 per QALY (for HBeAg-positive patients) for peginterferon alfa-2a then adefovir dipivoxil then lamivudine, compared with peginterferon alfa-2a then lamivudine then adefovir dipivoxil. # Consideration of the evidence The Committee reviewed the data available on the clinical and cost effectiveness of adefovir dipivoxil and peginterferon alfa-2a for the treatment of chronic hepatitis B, having considered evidence on the nature of the condition and the value placed on the benefits of adefovir dipivoxil and peginterferon alfa-2a by people with chronic hepatitis B, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources. The Committee considered that peginterferon alfa-2a was clinically and cost effective compared with interferon alfa therapy for the treatment of chronic hepatitis B on the basis of the cost effectiveness modelling. However, given that the difference in the rates of HBeAg seroconversion and ALT normalisation (HBeAg-positive chronic hepatitis B) compared with standard interferon alfa-2a were not statistically significant, the Committee was not persuaded that the potential advantages of peginterferon alfa-2a over standard interferon had been conclusively proven. The Committee concluded, therefore, that peginterferon alfa-2ashould be considered as an alternative to interferon alfa for the management of chronic hepatitis B during the initial phase of treatment. The experts stated that the effects of initial treatment with peginterferon alfa-2a in achieving a good response were different for HBeAg-positive and HBeAg-negative disease. The Committee was persuaded, however, that the response to peginterferon alfa-2a as measured by HBeAg seroconversion (in the case of HBeAg-positive disease) or an adequate reduction in viral load (in the case of HBeAg-negative disease) was clinically important in both cases. Thus the Committee concluded, on this basis, that peginterferon alfa-2a should be recommended as an option in first-line therapy for both HBeAg-positive and HBeAg-negative chronic hepatitis B. The Committee next considered the use of the oral antiviral agents (specifically adefovir dipivoxil) for the long-term treatment of both HBeAg-positive and HBeAg-negative chronic hepatitis B. The Committee considered the cost-effectiveness analysis presented by the assessment team on the use of adefovir dipivoxil compared with lamivudine in the long-term treatment of chronic hepatitis B. In addition the Committee discussed the cost-effectiveness analysis of the various treatment sequences that could be used over the entire disease process. It was apparent that adefovir dipivoxil was cost effective when compared directly with lamivudine for long-term therapy, if it was assumed that a switch could not be made to the alternative treatment if resistance developed. However, when considering the use of adefovir dipivoxil in the various treatment sequences, the Committee heard that the most cost-effective option was for it to be used following the emergence of viral resistance to lamivudine. The Committee heard the concerns of the clinical experts about the potential impact of the development of resistant viral mutations on future treatment options, based on the current experience of lamivudine use. The experts also stated that adefovir dipivoxil was less likely than lamivudine to result in viral resistance over the short term. They also expressed the view that viral resistance may be encouraged by the use of single agents and discussed with the Committee the possibility of recommending combination therapies for long-term treatment. The Committee was persuaded that it was likely that drug-resistance might be attenuated by using antiviral drugs in combination. The Committee felt unable to recommend routine use of combination therapies in the absence of trial evidence on the effect of combination therapy on drug resistance and its cost effectiveness. However, the Committee considered that it was not appropriate under these circumstances to recommend the use of adefovir dipivoxil only after resistance had already developed to another antiviral agent. It was persuaded by the expert testimony that it was possible to identify groups of people for whom lamivudine resistance is more likely to occur rapidly (for example, those with highly replicative disease), and those for whom development of lamivudine resistance is likely to have an adverse outcome (for example, those in whom a flare up of the infection may precipitate decompensated liver disease). Consequently it was sympathetic to the experts' view that it was appropriate to use adefovir dipivoxil for patients in whom the development of lamivudine-resistance would be considered particularly hazardous. The Committee was also sympathetic to the experts' view that under these circumstances the use of adefovir dipivoxil alone or in combination with lamivudine might be appropriate. The Committee concluded that it was appropriate to recommend adefovir dipivoxil as an option for the treatment of chronic hepatitis B for patients in whom prolonged oral antiviral treatment is required. It was also persuaded that this should be only after the use of an interferon as initial treatment unless this was contraindicated. The Committee was mindful that in the Assessment Group's economic model, the sequence of therapy with adefovir dipivoxil before lamivudine was not cost effective compared with the alternative of lamivudine followed by adefovir dipivoxil. The Committee was, however, persuaded that the decision to use adefovir dipivoxil (alone or in combination with lamivudine) would need to be made on a case-by-case basis. This should take into account various factors including HBeAg status, stage of disease process (for example the presence of compensated or decompensated cirrhosis) and the presence of, or likelihood of the emergence of, virus resistance. The Committee accepted consultee advice that drug treatment should be initiated only by a healthcare professional with expertise in the management of viral hepatitis, but that the task of continuing and monitoring therapy could be undertaken by general practitioners under shared-care arrangements.# Recommendations for further research There is considerable concern about viral resistance in the long-term treatment of chronic hepatitis B. Further research is needed on the role of combination therapy with antiviral drugs in reducing the development of resistance to treatment. There is at least one ongoing study comparing lamivudine alone with lamivudine in combination with adefovir dipivoxil in treatment-naive people with chronic hepatitis B.# Implications for the NHS Since the final appraisal determination was issued, NICE has carried out more detailed costing analysis to support implementation of the guidance. The following costing tools are available from the NICE website. A national costing report, which estimates the overall resource impact associated with implementation. A local costing template: a simple spreadsheet that can be used to estimate the local cost of implementation.# Related NICE guidance Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C. NICE technology appraisal guidance no. 75 (2004).# Review of guidance Because new drugs and drug combinations are likely to be licensed in the next 18 months, it is proposed that the guidance on this technology is considered for review in February 2007. Andrew DillonChief ExecutiveFebruary 2006# Appendix C. Detail on criteria for audit of the use of adefovir dipivoxil and peginterferon alfa-2a for chronic hepatitis B # Possible objectives for an audit An audit could be carried out to ensure that adefovir dipivoxil and peginterferon alfa-2a are being used appropriately for the treatment of people with chronic hepatitis B. # Possible patients to be included in the audit An audit could be carried out on a reasonable number of people being treated for chronic hepatitis B, for audit purposes, for example, patients seen over 6 months, excluding people with chronic hepatitis B who are known to be co-infected with hepatitis C, hepatitis D or HIV. # Measures that could be used as a basis for an audit The measures that could be used in an audit of adefovir dipivoxil and peginterferon alfa-2a for chronic hepatitis B are as follows. Criterion Standard Exception Definition of terms A. For an adult with chronic hepatitis B (HBeAg-positive or -negative), peginterferon alfa-2a is considered as an option for initial treatment in accordance with its licensed indications % of adults with chronic hepatitis B (HBeAg-positive or -negative) A. The person has a contra-indication to peginter-feron alfa-2a Clinicians will need to agree locally on how consideration of the options for treatment is documented for audit purposes. A contraindication is decompensated cirrhosis of the liver. See the 'Summary of product characteristics' for details of contraindications. . For an adult with chronic hepatitis B (HBeAg-positive or -negative), adefovir dipivoxil is considered as an option for treatment, in accordance with its licensed indications, if: a. treatment with interferon alfa or peginterferon alfa-2a has been unsuccessful or b. a relapse occurs after successful initial treatment or c. interferon alfa or peginterferon alfa-2a is poorly tolerated or contraindicated % of adults with chronic hepatitis B (HBeAg-positive or -negative) who meet any of 2a–2c B. The person has a contra-indication to adefovir dipivoxil Clinicians will need to agree locally on the sources of evidence for 2a–c and how consideration of the options for treatment is documented for audit purposes. 'Interferon alfa' includes interferon alfa-2a or -2b. 'Successful' treatment is considered to be treatment that leads to HBeAG seroconversion (in the case of HBeAg-positive disease) or an adequate reduction in viral load (in the case of HBeAg-negative disease). Clinicians will need to agree locally on how success of treatment is assessed, and how relapse after initial treatment and tolerance to adverse effects are documented for audit purposes. See the 'Summary of product characteristics' for details of contraindications. . Adefovir dipivoxil is given before treatment with lamivudine % of people with chronic hepatitis B for whom initial treatment options are being considered C. There is a clinical justification for treating with adefovir dipivoxil before lamivudine Clinicians will need to agree locally on clinical justifications for treating people with chronic hepatitis B with adefovir dipivoxil before lamivudine. . Adefovir dipivoxil is used either alone or in combination with lamivudine in either of the following circumstances: a. treatment with lamivudine has resulted in viral resistance or b. lamivudine resistance is likely to occur rapidly and development of lamivudine resistance is likely to have an adverse outcome % of the people with chronic hepatitis B for whom adefovir dipivoxil is being prescribed None Clinicians will need to agree locally on how treatment with lamivudine resulting in viral resistance and adverse outcomes are documented for audit purposes. An example of lamivudine resistance being likely to occur rapidly is the presence of highly replicative hepatitis B disease. An example of an adverse outcome is a flare of the infection that is likely to precipitate decompensated liver disease. . Drug treatment with peginterferon alfa-2a and adefovir dipivoxil is initiated by an appropriately qualified healthcare professional with expertise in the management of viral hepatitis % of people with chronic hepatitis B for whom peginterferon alfa-2a or adefovir dipivoxil is prescribed None Clinicians will need to agree locally on the definition of an appropriately qualified healthcare professional with expertise in the management of viral hepatitis, for audit purposes. # Calculation of compliance Compliance (%) with each measure described in the table above is calculated as follows. Number of patients whose care is consistent with the criterion plus number of patients who meet any exception listed x 100 Number of patients to whom the measure applies Clinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.# Changes after publication March 2014: implementation section updated to clarify that adefovir dipivoxil and peginterferon alfa-2a are recommended as options for treating chronic hepatitis B. Additional minor maintenance update also carried out. June 2013: Recommendations 1.2–1.4 replaced by recommendations 1.5.13–1.5.15 in Hepatitis B (chronic): diagnosis and management of chronic hepatitis B in children, young people and adults (NICE clinical guideline 165). March 2012: minor maintenance# About this guidance NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales. This guidance was developed using the NICE multiple technology appraisal process. It has been updated by NICE clinical guideline 165 (published June 2013) and incorporated into the NICE pathway on hepatitis B (chronic) in the antiviral treatment in adults with chronic hepatitis B path along with other related guidance and products. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.	{'Guidance': 'This guidance was partially updated by NICE clinical guideline 165 in June 2013. See About this guidance for more information.\n\nThis guidance does not apply to people with chronic hepatitis\xa0B known to be co-infected with hepatitis\xa0C, hepatitis\xa0D or HIV.\n\nPeginterferon alfa-2a is recommended as an option for the initial treatment of adults with chronic hepatitis\xa0B (HBeAg-positive or HBeAg-negative), within its licensed indications.\n\nThis recommendation has been replaced by recommendation 1.5.13 in NICE clinical guideline 165.\n\nThis recommendation has been replaced by recommendation 1.5.14 in NICE clinical guideline 165.\n\nThis recommendation has been replaced by recommendation 1.5.15 in NICE clinical guideline 165.', 'Clinical need and practice': "Chronic hepatitis B is defined as viraemia and hepatic inflammation that persists for more than 6 months after acute infection with hepatitis\xa0B virus. Hepatitis\xa0B virus is transmitted by sexual contact, through the use of infected blood and blood products, by reuse of contaminated needles and syringes, by vertical transmission from mother to child during, or soon after, birth, and by horizontal transmission among children. The risk of chronic infection with hepatitis\xa0B virus depends on the nature of the immune response to the initial infection. This varies according to the age at which the infection is acquired. Almost 100% of neonates, and about 50% of young children, develop chronic hepatitis B if infected with hepatitis\xa0B virus. In contrast, only about 2–10% of people who are infected as adults go on to develop chronic hepatitis\xa0B.\n\nThe Department of Health estimates that about 180,000 people in the UK have chronic hepatitis\xa0B. There are about 7700 new cases of chronic hepatitis\xa0B each year. Of these, around 300 people were infected within the UK; the remainder (mainly immigrants to the UK) were infected abroad, generally in areas of high prevalence where the virus is frequently transmitted from mother to child.\n\nPeople with active chronic hepatitis\xa0B are at increased risk of liver cirrhosis (scarring of the liver tissue that may progress to liver failure) and primary liver cancer (hepatocellular carcinoma).\n\nThe diagnosis of chronic hepatitis\xa0B is based on the presence of well-characterised serological markers in the blood. Hepatitis\xa0B viral DNA (HBV\xa0DNA) is present in both acute and chronic hepatitis B. Hepatitis\xa0B surface antigen (HBsAg) is a viral protein detectable in the blood in both acute and chronic infection. Chronic hepatitis\xa0B is defined as persistence of HBsAg for 6\xa0months or more after acute infection. Hepatitis B 'e' antigen (HBeAg) is an indicator of viral replication, although some variant forms of the virus do not express HBeAg (see section 2.5.5 below). Active infection can be described as HBeAg-positive or HBeAg-negative according to whether HBeAg is secreted.\n\nThe natural history of chronic hepatitis\xa0B can be divided into phases, each of which may last many years.\n\nImmunotolerant phase.People who are affected at birth or in early childhood initially enter an 'immunotolerant' phase during which the immune system does not actively fight the virus. The virus replicates rapidly during this phase, but the person usually has no symptoms. The person is highly infectious, and may infect other members of the family and community. This phase can last for many years before progressing to active disease.\n\nIncubation. The incubation period for hepatitis B infection ranges from 40–160 days, with an average of 60–90 days.\n\nActive chronic hepatitis\n B.The first stage of active disease involves a period of increasing inflammatory hepatic necrosis as the immune system begins to fight the virus. This stage of the disease is characterised by elevated levels of viral DNA in the blood, persistently raised levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and evidence of hepatic necrosis and inflammation on biopsy. The liver damage caused by infection and inflammation may eventually lead to cirrhosis of the liver. Progression to cirrhosis occurs at an annual rate of 2–5.5%, with a cumulative 5-year rate of progression of 8–20%.\n\nHBeAg seroconversion\n \n .\n In people infected with an HBeAg-positive form of the virus, the next stage of the infection occurs when inflammation becomes sufficiently intense to cause lysis of infected hepatocytes. This produces a 'flare' of the disease with symptoms resembling acute hepatitis B, and leads to the development of antibodies against the 'e'\xa0antigen. This is referred to as 'HBeAg seroconversion'. The seroconverted disease state is associated with good quality of life and a relatively low risk of disease progression. It is referred to as the 'inactive HBsAg carrier state' because patients continue to express hepatitis\xa0B surface antigen (HBsAg). The spontaneous seroconversion rate is 5–10% per year, although this varies among populations. Once seroconversion has taken place, most people remain in the inactive HBsAg carrier state. However, increasing viraemia and recurrent hepatitis after seroconversion indicate the emergence of the HBeAg-negative strain of the virus.\n\nHBeAg-negative chronic hepatitis B\n \n .\n In recent years a form of the virus that does not cause infected cells to secrete HBeAg has been discovered (sometimes called the 'precore mutant' strain). People can be infected with the so-called HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in people initially infected with the HBeAg-positive form of the virus. The prevalence of HBeAg-negative hepatitis varies geographically; it is more common in Asia and the Mediterranean region than in Northern Europe. Infection with HBeAg-negative chronic hepatitis\xa0B is associated with a fluctuating course and a poor prognosis. Active disease is associated with either persistent elevation of ALT or an erratic pattern of ALT changes with flare-ups resembling acute hepatitis\xa0B that can be severe or even fatal. Few patients with HBeAg-negative chronic hepatitis\xa0B achieve a lasting remission. Progression to cirrhosis of the liver has been estimated to occur in 8-10% of people with HBeAg-negative chronic hepatitis\xa0B each year.\n\nHBsAg seroconversion.The development of antibodies against HBsAg, with clearance of HBsAg, occurs spontaneously in about 0.5–2% of people with chronic hepatitis\xa0B each year in western countries. In countries where hepatitis\xa0B is endemic, the rate is much lower – between 0.05 and 0.08% per year. Clearance of HBsAg is most likely to occur in the year following HBeAg seroconversion. It signifies resolution of the chronic infection. Variants of hepatitis B (known as 'occult hepatitis B') that are not associated with detectable HBsAg by current immunoassays have been recognised.\n\nThe aim of treatment is to prevent progression to cirrhosis or hepatocellular carcinoma. Treatment may be given as a finite course (circumscribed therapy) – with the intention of allowing the immune system to respond and control the infection without the need for further drug treatment – or as long-term viral suppressive therapy. Long-term therapy is needed if short-term therapy is unsuccessful.\n\nThe first drugs to be licensed for the treatment of chronic hepatitis\xa0B were alfa interferons. Interferons are natural proteins that activate the immune system in response to viral infection. Three recombinant interferon products have UK marketing authorisation for the treatment of chronic hepatitis\xa0B: IntronA (interferon alfa-2b, Schering-Plough), Roferon-A (interferon alfa-2a, Roche) and Viraferon (interferon alfa-2b, Schering-Plough). Interferon alfa-2a is usually given at a dose of 2.5–5\xa0million units per square metre of body surface area by subcutaneous injection three times a week for 4–6 months. Interferon alfa-2b is given at a dose of 5–10\xa0million units three times a week for 4–6\xa0months. The side effects of interferons can be severe and this means that they are not suitable for long-term treatment in chronic hepatitis\xa0B. Interferons are contraindicated in decompensated liver disease. There are no data on long-term maintenance therapy with an alfa interferon and the treatment is not licensed for this.\n\nLamivudine (Zeffix, GlaxoSmithKline) is a nucleoside reverse transcriptase inhibitor antiviral drug. The dose in adults is 100\xa0mg per day. It can be given both as a circumscribed course of treatment or as long-term viral suppressive therapy. In HBeAg-positive chronic hepatitis\xa0B, treatment is usually given for a year with the aim of bringing about HBeAg seroconversion. In HBeAg-negative chronic hepatitis\xa0B, a circumscribed course of therapy is less likely to lead to long-term control of the infection, and long-term treatment is often needed. The main problem with long-term antiviral treatment is the emergence of resistance. Resistance to lamivudine occurs in more than 60% of cases after 3\xa0years' treatment.", 'The technologies': "# Peginterferon alfa-2a\n\nPeginterferon alfa-2a (Pegasys, Roche) has UK marketing authorisation for the treatment of HBeAg-positive or HBeAg-negative chronic hepatitis B in adults with compensated liver disease and evidence of viral replication, increased ALT and histologically verified liver inflammation and/or fibrosis. Peginterferons are formed by attaching strands of polyethylene glycol (PEG) to the interferon molecules. This slows the rate of absorption and excretion of interferon, reducing the fluctuations in serum level that occur with unmodified interferon. Peginterferons are administered once a week, compared with three or more times a week for the unmodified form.\n\nPeginterferons have a range of adverse effects similar to those of interferons. These include influenza-like symptoms such as fever, chills, myalgias, arthralgias and headache, which are most likely to occur at the start of treatment and seldom require discontinuation of treatment. Depletion of platelets and white blood cells is common. Other adverse effects include depression, anxiety or emotional lability, which may be severe. Cardiovascular adverse effects include hypertension or hypotension, arrhythmias, oedema, myocardial infarction or stroke. Interferons are contraindicated in chronic hepatitis with decompensated cirrhosis of the liver. For full details of side effects and contraindications, see the 'Summary of product characteristics'.\n\nA prefilled syringe containing 180\xa0micrograms of peginterferon alfa-2a costs £132.06 (excluding VAT, 'British national formulary', 50th edition ['BNF'50]). The usual dose is 180\xa0micrograms once a week. Costs may vary in different settings because of negotiated procurement discounts.\n\n# Adefovir dipivoxil\n\nAdefovir is structurally related to the purine base adenine. It is converted intracellularly to the diphosphate, which inhibits the synthesis of hepatitis B virus DNA through competition for the enzyme reverse transcriptase and incorporation into the viral DNA. Adefovir is not well absorbed after oral administration so is given by mouth as the prodrug adefovir dipivoxil.\n\nAdefovir dipivoxil (Hepsera, Gilead) has UK marketing authorisation for the treatment of chronic hepatitis B in adults with:\n\ncompensated liver disease with evidence of active viral replication, persistently elevated serum ALT levels and histological evidence of active liver inflammation and fibrosis\n\ndecompensated liver disease.\n\nThe most commonly reported adverse effects for adefovir dipivoxil are gastrointestinal effects including nausea, flatulence, diarrhoea and dyspepsia. Increases in serum creatinine are common but usually mild to moderate. However, cases of renal impairment and acute renal failure have been reported. For full details of side effects and contraindications, see the 'Summary of product characteristics'.\n\nA pack containing 30 days' supply of adefovir dipivoxil 10\xa0mg tablets costs £315.00 (excluding VAT, 'BNF'50). Costs may vary in different settings because of negotiated procurement discounts.", 'Evidence and interpretation': "The Appraisal Committee (appendix A) considered evidence from a number of sources (appendix B).\n\n# Clinical effectiveness\n\n## Peginterferon alfa-2a\n\nThe Assessment Group found three randomised controlled trials investigating peginterferon alfa-2a in chronic hepatitis\xa0B. Two trials were in people with HBeAg-positive chronic hepatitis\xa0B, and the third was in people with HBeAg-negative chronic hepatitis\xa0B.\n\nIn HBeAg-positive chronic hepatitis\xa0B, the most useful measure of response is HBeAg loss or seroconversion because this signals transition to the inactive carrier state, which is associated with a relatively benign outcome. The rate of HBeAg seroconversion was reported in both studies of peginterferon alfa-2a in HBeAg-positive chronic hepatitis\xa0B.\n\nOne trial was an open-label study in which 194 participants were randomised to one of three doses of peginterferon alfa-2a or interferon alfa-2a. Treatment was for 24\xa0weeks, and was followed by 24-weeks' treatment-free follow-up. The rate of HBeAg seroconversion was higher in the patients treated with peginterferon alfa-2a (32% for all three doses combined) than in patients treated with interferon alfa-2a (25%), but the difference was not statistically significant. ALT levels were also more likely to return to the normal range in the people treated with peginterferon alfa-2a (36% for all three doses combined compared with 25% for interferon alfa-2a). This difference was also not statistically significant. The only statistically significant difference between treatment and control in this trial was for the rate of 'combined response', defined as HBeAg loss, HBV DNA normalisation and ALT normalisation (24% for all three treatment doses combined compared with 12% for control, p\xa0=\xa00.036).\n\nThe second trial in patients with HBeAg-positive chronic hepatitis\xa0B was a comparison of peginterferon alfa-2a with lamivudine, in which 814 people were randomised to peginterferon alfa-2a plus placebo, peginterferon alfa-2a plus lamivudine, or lamivudine alone. The study was partially double blind in that those who were receiving peginterferon alfa-2a were blinded as to whether they were receiving lamivudine. Treatment was for 48\xa0weeks, and was followed by 24-weeks' treatment-free follow-up. The rate of HBeAg seroconversion at week 72 was significantly higher in the patients treated with peginterferon alfa-2a plus placebo (32%) than in those treated with lamivudine alone (19%), p\xa0<\xa00.001. Addition of lamivudine to peginterferon alfa-2a did not improve the HBeAg seroconversion rate over peginterferon alfa-2a alone: the rate in the group that received both lamivudine and peginterferon alfa-2a was 27%. Normalisation of ALT occurred in a higher proportion of the group taking peginterferon alfa-2a than of the group taking lamivudine alone (41% versus 28%, p\xa0=\xa00.002). Again, adding lamivudine to peginterferon alfa-2a did not improve the response rate for this endpoint (ALT normalisation 39%).\n\nIn HBeAg-negative chronic hepatitis\xa0B, a major objective of treatment is suppressing viral replication and preventing progressive liver disease. In clinical trials these outcomes have usually been expressed in terms of decrease in the levels of HBV\xa0DNA found in the serum and ALT normalisation.\n\nThe only study of peginterferon alfa-2a in HBeAg-negative chronic hepatitis\xa0B was a three-way comparison of peginterferon alfa-2a plus placebo, peginterferon alfa-2a plus lamivudine, and lamivudine alone (n\xa0=\xa0537). Treatment was for 48\xa0weeks and was followed by 24-weeks' treatment-free follow up (72\xa0weeks in total). The study had two predetermined primary measures of efficacy: the normalisation of ALT levels and the suppression of HBV\xa0DNA levels to less than 20,000\xa0copies/ml. At week\xa072, the percentage with normalised ALT was significantly higher in the groups treated with peginterferon alfa-2a than in the lamivudine group (59% with peginterferon alfa-2a monotherapy and 60% for peginterferon alfa-2a plus lamivudine, versus 44% for lamivudine; p\xa0=\xa00.004 and p\xa0=\xa00.003 respectively). For the outcome of virological response (HBV\xa0DNA\xa0<\xa020,000 copies/ml) at week 72, the percentage of patients who had a response was significantly higher in the groups treated with peginterferon alfa-2a than in the lamivudine group (43% for peginterferon alfa-2a monotherapy and 44% for peginterferon alfa-2a plus lamivudine, versus 29% for lamivudine; p\xa0=\xa00.007 and p\xa0=\xa00.003 respectively).\n\nTreatment-resistance mutations were detected in 32 people (18%) in the lamivudine group and one person (<\xa01%) in the peginterferon alfa-2a plus lamivudine group (p\xa0<\xa00.001).\n\n## Adefovir dipivoxil\n\nThe assessment report included five randomised controlled trials of adefovir dipivoxil in chronic hepatitis\xa0B. Four of the studies were conducted in people with HBeAg-positive chronic hepatitis\xa0B and one was in people with HBeAg-negative chronic hepatitis\xa0B.\n\nThe largest study (n\xa0=\xa0515) was a comparison of two doses of adefovir dipivoxil (10\xa0mg and 30\xa0mg) with placebo in people with HBeAg-positive chronic hepatitis\xa0B and compensated liver disease. The primary endpoint was histological improvement (defined in terms of a reduction in Knodell necroinflammatory score). Histological improvement was seen in 59% of patients in the adefovir dipivoxil 30\xa0mg group, 53% of patients in the adefovir dipivoxil 10\xa0mg group and 25% of patients in the placebo group (p\xa0<\xa00.001 for both comparisons with placebo). The HBeAg seroconversion rates were 14% for the adefovir dipivoxil 30\xa0mg group, 12% for the adefovir dipivoxil 10\xa0mg group and 6%, for the placebo group. The rates of ALT normalisation were 55% for the 30\xa0mg, 48% for the 10\xa0mg and 16% for the placebo group.\n\nAnother study (n\xa0=\xa059) investigated adefovir dipivoxil in people with HBeAg-positive chronic hepatitis\xa0B, genotypic evidence of lamivudine-resistance, raised ALT and a serum HBV\xa0DNA level of at least 106\xa0copies/ml despite ongoing treatment with lamivudine. The patients were randomised to adefovir dipivoxil 10\xa0mg, lamivudine 100\xa0mg, or the addition of adefovir dipivoxil to ongoing lamivudine treatment. The primary endpoint was time-weighted change from baseline in serum HBV\xa0DNA level. Reductions in this endpoint were seen in all recipients of adefovir dipivoxil. HBV\xa0DNA levels were 'undetectable' (<\xa01000\xa0copies/ml) in 26% of patients receiving adefovir dipivoxil plus placebo, in 35% of patients receiving adefovir dipivoxil plus lamivudine, and in none of the patients receiving lamivudine plus placebo (p\xa0=\xa00.005). ALT was normalised in 53% of the adefovir dipivoxil plus lamivudine group and 47% of adefovir dipivoxil group, compared with 5% (1/19) of the lamivudine group (p\xa0=\xa00.001 and p\xa0=\xa00.004, respectively)\n\nThe remaining two studies in HBeAg-positive chronic hepatitis\xa0B investigated the combination of adefovir dipivoxil with lamivudine compared with lamivudine alone. One was in treatment-naive patients (n\xa0=\xa0112) and the other was in patients with lamivudine resistance (n\xa0=\xa094). In the study in treatment-naive patients (which was still ongoing at the time of this appraisal) there was no advantage in adding adefovir dipivoxil to lamivudine at 1 year in terms of virological, serological or biochemical outcome. However, there was a higher incidence of lamivudine-resistance mutations and viral breakthrough in the group that received lamivudine alone. In the other study of patients with lamivudine resistance, adefovir dipivoxil plus lamivudine was more effective than lamivudine alone in terms of both virological and ALT responses. HBV\xa0DNA level fell to 105\xa0copies/ml or less in 85% of those taking adefovir dipivoxil plus lamivudine, compared with 11% of patients taking lamivudine alone (p\xa0<\xa00.001). ALT was normalised in 37% of those taking the combined treatment, compared with 9% of those taking lamivudine (p\xa0=\xa00.003).\n\nOne study compared adefovir dipivoxil with placebo in people with HBeAg-negative chronic hepatitis\xa0B. This was a double-blind study in which 185\xa0people were randomised in a 2:1 ratio to adefovir dipivoxil or placebo for 48\xa0weeks. The primary endpoint was histological improvement defined in terms of a reduction in Knodell necroinflammatory score with no worsening of fibrosis. A total of 167\xa0patients (91%) had assessable pre-treatment and post-treatment liver biopsy specimens. Significantly more patients had histological improvement in the adefovir dipivoxil group than in the placebo group (64% versus 33%, p\xa0<\xa00.001). At week\xa048, 51% of the adefovir dipivoxil group had undetectable HBV\xa0DNA levels (<\xa0400 copies/ml), compared with no one in the placebo group (p\xa0<\xa00.001), and 72% had normalised ALT levels compared with 29% in the placebo group (p\xa0<\xa00.001).\n\nLong-term follow-up data have been published recently. After week\xa048, 123\xa0people who had been assigned to adefovir dipivoxil in the initial study were randomised to continue adefovir dipivoxil at a dose of 10\xa0mg daily or to switch to placebo. Of the 61\xa0patients who had initially been randomised to placebo, 60 switched to treatment with adefovir dipivoxil 10\xa0mg daily. At week\xa096, HBV\xa0DNA was undetectable in 71% of the group continuing with adefovir dipivoxil, compared with 8% of the placebo group. In the group who received adefovir dipivoxil for 48\xa0weeks having previously received placebo for 48\xa0weeks, HBV\xa0DNA was undetectable in 76% of patients. The cumulative incidence of resistance to adefovir dipivoxil among all patients was 3% at 96\xa0weeks and 5.9% at 144\xa0weeks. This trial will continue until all patients have completed 5\xa0years' follow-up.\n\n## Evidence from clinical experts\n\nThe Committee heard from the clinical experts that the decision to treat chronic hepatitis\xa0B was determined by the degree of fibrosis and/or necroinflammation on liver biopsy, combined with evidence of active viral replication (HBV\xa0DNA levels) and the persistent elevation of serum ALT. Treatment was not necessarily indicated for people with minimal elevation of ALT (1.5–2.0 times the upper limit of normal) and low necroinflammatory scores on liver biopsy. However, these people should be carefully monitored because the disease can change rapidly from a quiescent to an active state.\n\nThe experts expressed concern about the development of viruses with mutations rendering them resistant to antiviral drugs. Lamivudine resistance develops in a high proportion of patients on monotherapy, and could limit the options for future treatment through cross-resistance to related drugs. The experts noted that a strategy of treating chronic hepatitis\xa0B with lamivudine followed by adefovir dipivoxil for those in whom lamivudine-resistance developed reflected current practice. However, the experts noted that there was a subgroup of people with highly replicative disease in whom resistance could develop rapidly; in these people, a strategy of using adefovir dipivoxil in combination with lamivudine might be appropriate.\n\nIn principle, the use of combination therapies should minimise the risk of developing resistant variants, although long-term follow-up data from studies are lacking. The clinical experts stressed the need for further research on the long-term effectiveness of combination regimens in preventing resistance.\n\n# Cost effectiveness\n\nThe Committee considered evidence from four economic models: one by the Assessment Group, one by each of the two manufacturers involved, and one published analysis by Kanwal and colleagues (which was published after the Assessment Report's deadline for inclusion). The models have similar structures and parameters, and their results are in broad agreement.\n\n## Assessment Group model\n\nThe Assessment Group model presents analyses for people with HBeAg-positive disease and HBeAg-negative disease separately, and also as a single group, with proportions of people with HBeAg-positive disease and HBeAg-negative disease determined from the parameters of the model.\n\nResults are presented for peginterferon alfa-2a (48\xa0weeks' treatment) compared with interferon alfa-2a (24\xa0weeks for HBeAg-positive disease or 48\xa0weeks for HBeAg-negative disease), and for adefovir dipivoxil compared with lamivudine. The incremental cost-effectiveness ratios (ICERs) for these two comparisons in HBeAg-positive and HBeAg-negative groups combined were £6100 and £16,500 per quality-adjusted life year (QALY) respectively. However, this analysis assumes that, if the first therapy does not produce a sustained response, people receive no further treatment other than best supportive care, whereas in practice people may go on to receive treatment with an alternative agent. The Assessment Group therefore produced an analysis that considered more clinically relevant scenarios in which people could receive a sequence of drug treatments as necessary.\n\nIt is assumed that all patients are first given a course of treatment with either interferon alfa-2a (for 24 or 48\xa0weeks, depending on HBeAg status) or peginterferon alfa-2a for 48\xa0weeks. If HBeAg or HBsAg seroconversion occurs on one of the interferons, the patients are assumed to take no further antiviral medication; if not, they proceed to one of the following sequences of treatment, which form the basis of the comparison:\n\nbest supportive care, that is, no further antiviral medication\n\nlamivudine, then best supportive care on seroconversion or development of resistance\n\nadefovir dipivoxil, then best supportive care on seroconversion or development of resistance\n\nlamivudine, then adefovir dipivoxil on development of resistance, then best supportive care on seroconversion or development of resistance.\n\nThe Assessment Group analysis also reports ICERs for the use of lamivudine then best supportive care without first using an interferon, and of adefovir dipivoxil then best supportive care without first using an interferon. It did not report on sequences of both lamivudine and adefovir dipivoxil that were not preceded by an interferon. However, because of the underlying assumptions used in the model, these ICERs can be inferred from the equivalent comparisons for sequences including peginterferon alfa-2a or interferon\xa0alfa-2a.\n\nComparing these sets of sequences generated a large number of ICER estimates. However, some of the strategies can be excluded from consideration using the notion of dominance or extended dominance. This means that when strategies A, B and C (in order of increasing cost) are compared, if the ICER for B compared with A is higher than that for C compared with A, and if the benefits of B are less than those of C, then B is excluded.\n\nFor HBeAg-positive disease, the treatment sequences that are not excluded by extended dominance are as follows:\n\nlamivudine then best supportive care (estimated ICER £3500 per QALY compared with best supportive care)\n\ninterferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care (estimated ICER £9900 per QALY compared with lamivudine then best supportive care)\n\npeginterferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care (estimated ICER £18,800 per QALY compared with interferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care)\n\npeginterferon alfa-2a then adefovir dipivoxil then lamivudine then best supportive care (estimated ICER £57,000 per QALY compared with peginterferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care). Note that this treatment sequence did not appear in the Assessment Report, but was prepared by the Assessment Group for the Appraisal Committee before its first meeting.\n\nFor HBeAg-negative disease, the treatment sequences that are not excluded by extended dominance are as follows:\n\npeginterferon alfa-2a then best supportive care (estimated ICER £3000 per QALY compared with best supportive care)\n\npeginterferon alfa-2a then lamivudine then best supportive care (estimated ICER £4900 per QALY compared with peginterferon alfa-2a then best supportive care)\n\npeginterferon alfa-2a then lamivudine then adefovir dipivoxil then best supportive care (estimated ICER £18,000 per QALY compared with peginterferon alfa-2a then lamivudine then best supportive care).\n\n## Manufacturer's model (Roche)\n\nThe model submitted by Roche reports a number of estimated cost effectiveness results, all involving either interferon alfa-2a or peginterferon alfa-2a, for HBeAg-positive and HBeAg-negative disease separately. Nothing is said about later choices for people for whom the interferon has not been clinically effective. The estimated ICERs for people with HBeAg-positive disease are as follows:\n\npeginterferon alfa-2a for 24\xa0weeks compared with interferon alfa-2a for 24\xa0weeks (ICER £2700 per QALY)\n\npeginterferon alfa-2a for 48\xa0weeks compared with interferon alfa-2a for 24\xa0weeks (ICER £13,900 per QALY)\n\npeginterferon alfa-2a for 48\xa0weeks compared with lamivudine for 48\xa0weeks (ICER £5300 per QALY)\n\npeginterferon alfa-2a for 48\xa0weeks compared with lamivudine for 208\xa0weeks (ICER £5900 per QALY)\n\npeginterferon alfa-2a for 48\xa0weeks compared with adefovir dipivoxil for 48\xa0weeks (ICER £1400 per QALY)\n\npeginterferon alfa-2a for 48\xa0weeks compared with adefovir dipivoxil for 208\xa0weeks (dominant, that is, greater benefit at lower cost than adefovir dipivoxil)\n\npeginterferon alfa-2a for 48\xa0weeks compared with no treatment (ICER £2800 per QALY).\n\nThe ICERs for people with HBeAg-negative disease are as follows:\n\npeginterferon alfa-2a for 48\xa0weeks compared with lamivudine for 48\xa0weeks (ICER £3200 per QALY)\n\npeginterferon alfa-2a for 48\xa0weeks compared with lamivudine for 208\xa0weeks (ICER £1900 per QALY)\n\npeginterferon alfa-2a for 48\xa0weeks compared with no treatment (ICER £1500 per QALY).\n\n## Manufacturer's model (Gilead)\n\nThe model submitted by Gilead presents estimated cost-effectiveness ratios for a number of single treatments and treatment sequences. However, the cost effectiveness of adefovir dipivoxil compared with best supportive care is not reported. The interferons are not considered as treatment options, and the analyses are for a combined population of people with HBeAg-positive and HBeAg-negative disease. The estimated ICERs are as follows:\n\nlamivudine then adefovir dipivoxil (when lamivudine resistance emerges) compared with best supportive care – ICER £6700 per QALY\n\nlamivudine then adefovir dipivoxil (when lamivudine resistance emerges) compared with lamivudine then best supportive care (when lamivudine resistance emerges) – ICER £9200 per QALY\n\nadefovir dipivoxil then lamivudine (when adefovir dipivoxil resistance emerges) compared with best supportive care – ICER £8200 per QALY\n\nadefovir dipivoxil then lamivudine (when adefovir dipivoxil resistance emerges) compared with lamivudine then best supportive care (when lamivudine resistance emerges) – ICER £11,400 per QALY\n\nadefovir dipivoxil then lamivudine (when adefovir dipivoxil resistance emerges) compared with lamivudine then adefovir dipivoxil (when lamivudine resistance emerges) – ICER £29,400 per QALY.\n\n## Published model\n\nThe published model (Kanwal and colleagues) evaluated a 'do nothing' strategy (equivalent to best supportive care), interferon alfa, lamivudine, adefovir dipivoxil, and lamivudine then adefovir dipivoxil. For HBeAg-positive disease, the estimated ICERs for the non-dominated strategies are as follows:\n\ninterferon alfa compared with best supportive care – ICER $2300 (£1300 at an exchange rate of $1.75 per £1) per QALY\n\nlamivudine then adefovir dipivoxil, compared with interferon alfa – ICER $16,600 (£9500) per QALY\n\nadefovir dipivoxil, compared with lamivudine then adefovir dipivoxil) – ICER $91,000 (£52,000) per QALY.\n\nIn the analysis for HBeAg-negative disease, lamivudine then adefovir dipivoxil (as salvage therapy after resistance to lamivudine develops) is both cheaper and more effective than all other treatment options.\n\n## Overall results of the models\n\nThe models show that interferon alfa or peginterferon alfa-2a therapies followed by lamivudine then adefovir dipivoxil, where necessary, appear to be cost effective relative to alternative strategies. In most of the analyses, strategies in which adefovir dipivoxil is used before lamivudine, or without lamivudine, in the sequence are dominated by the alternative strategies. The exceptions are Gilead's estimated ICER of £29,400 per QALY for adefovir dipivoxil then lamivudine, compared with lamivudine then adefovir dipivoxil, and the Assessment Group's estimated ICER of £57,000 per QALY (for HBeAg-positive patients) for peginterferon alfa-2a then adefovir dipivoxil then lamivudine, compared with peginterferon alfa-2a then lamivudine then adefovir dipivoxil.\n\n# Consideration of the evidence\n\nThe Committee reviewed the data available on the clinical and cost effectiveness of adefovir dipivoxil and peginterferon alfa-2a for the treatment of chronic hepatitis\xa0B, having considered evidence on the nature of the condition and the value placed on the benefits of adefovir dipivoxil and peginterferon alfa-2a by people with chronic hepatitis\xa0B, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources.\n\nThe Committee considered that peginterferon alfa-2a was clinically and cost effective compared with interferon alfa therapy for the treatment of chronic hepatitis\xa0B on the basis of the cost effectiveness modelling. However, given that the difference in the rates of HBeAg seroconversion and ALT normalisation (HBeAg-positive chronic hepatitis\xa0B) compared with standard interferon alfa-2a were not statistically significant, the Committee was not persuaded that the potential advantages of peginterferon\xa0alfa-2a over standard interferon had been conclusively proven. The Committee concluded, therefore, that peginterferon alfa-2ashould be considered as an alternative to interferon alfa for the management of chronic hepatitis\xa0B during the initial phase of treatment.\n\nThe experts stated that the effects of initial treatment with peginterferon alfa-2a in achieving a good response were different for HBeAg-positive and HBeAg-negative disease. The Committee was persuaded, however, that the response to peginterferon alfa-2a as measured by HBeAg seroconversion (in the case of HBeAg-positive disease) or an adequate reduction in viral load (in the case of HBeAg-negative disease) was clinically important in both cases. Thus the Committee concluded, on this basis, that peginterferon alfa-2a should be recommended as an option in first-line therapy for both HBeAg-positive and HBeAg-negative chronic hepatitis\xa0B.\n\nThe Committee next considered the use of the oral antiviral agents (specifically adefovir dipivoxil) for the long-term treatment of both HBeAg-positive and HBeAg-negative chronic hepatitis\xa0B. The Committee considered the cost-effectiveness analysis presented by the assessment team on the use of adefovir dipivoxil compared with lamivudine in the long-term treatment of chronic hepatitis\xa0B. In addition the Committee discussed the cost-effectiveness analysis of the various treatment sequences that could be used over the entire disease process. It was apparent that adefovir dipivoxil was cost effective when compared directly with lamivudine for long-term therapy, if it was assumed that a switch could not be made to the alternative treatment if resistance developed. However, when considering the use of adefovir dipivoxil in the various treatment sequences, the Committee heard that the most cost-effective option was for it to be used following the emergence of viral resistance to lamivudine.\n\nThe Committee heard the concerns of the clinical experts about the potential impact of the development of resistant viral mutations on future treatment options, based on the current experience of lamivudine use. The experts also stated that adefovir dipivoxil was less likely than lamivudine to result in viral resistance over the short term. They also expressed the view that viral resistance may be encouraged by the use of single agents and discussed with the Committee the possibility of recommending combination therapies for long-term treatment.\n\nThe Committee was persuaded that it was likely that drug-resistance might be attenuated by using antiviral drugs in combination. The Committee felt unable to recommend routine use of combination therapies in the absence of trial evidence on the effect of combination therapy on drug resistance and its cost effectiveness. However, the Committee considered that it was not appropriate under these circumstances to recommend the use of adefovir dipivoxil only after resistance had already developed to another antiviral agent. It was persuaded by the expert testimony that it was possible to identify groups of people for whom lamivudine resistance is more likely to occur rapidly (for example, those with highly replicative disease), and those for whom development of lamivudine resistance is likely to have an adverse outcome (for example, those in whom a flare up of the infection may precipitate decompensated liver disease). Consequently it was sympathetic to the experts' view that it was appropriate to use adefovir dipivoxil for patients in whom the development of lamivudine-resistance would be considered particularly hazardous. The Committee was also sympathetic to the experts' view that under these circumstances the use of adefovir dipivoxil alone or in combination with lamivudine might be appropriate.\n\nThe Committee concluded that it was appropriate to recommend adefovir dipivoxil as an option for the treatment of chronic hepatitis\xa0B for patients in whom prolonged oral antiviral treatment is required. It was also persuaded that this should be only after the use of an interferon as initial treatment unless this was contraindicated. The Committee was mindful that in the Assessment Group's economic model, the sequence of therapy with adefovir dipivoxil before lamivudine was not cost effective compared with the alternative of lamivudine followed by adefovir dipivoxil. The Committee was, however, persuaded that the decision to use adefovir dipivoxil (alone or in combination with lamivudine) would need to be made on a case-by-case basis. This should take into account various factors including HBeAg status, stage of disease process (for example the presence of compensated or decompensated cirrhosis) and the presence of, or likelihood of the emergence of, virus resistance.\n\nThe Committee accepted consultee advice that drug treatment should be initiated only by a healthcare professional with expertise in the management of viral hepatitis, but that the task of continuing and monitoring therapy could be undertaken by general practitioners under shared-care arrangements.", 'Recommendations for further research': 'There is considerable concern about viral resistance in the long-term treatment of chronic hepatitis\xa0B. Further research is needed on the role of combination therapy with antiviral drugs in reducing the development of resistance to treatment. There is at least one ongoing study comparing lamivudine alone with lamivudine in combination with adefovir dipivoxil in treatment-naive people with chronic hepatitis\xa0B.', 'Implications for the NHS ': 'Since the final appraisal determination was issued, NICE has carried out more detailed costing analysis to support implementation of the guidance. The following costing tools are available from the NICE website.\n\nA national costing report, which estimates the overall resource impact associated with implementation.\n\nA local costing template: a simple spreadsheet that can be used to estimate the local cost of implementation.', 'Related NICE guidance': 'Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C.\n NICE technology appraisal guidance no. 75 (2004).', 'Review of guidance': 'Because new drugs and drug combinations are likely to be licensed in the next 18 months, it is proposed that the guidance on this technology is considered for review in February 2007.\n\nAndrew DillonChief ExecutiveFebruary 2006', 'Appendix C. Detail on criteria for audit of the use of adefovir dipivoxil and peginterferon alfa-2a for chronic hepatitis B': "# Possible objectives for an audit\n\nAn audit could be carried out to ensure that adefovir dipivoxil and peginterferon alfa-2a are being used appropriately for the treatment of people with chronic hepatitis B.\n\n# Possible patients to be included in the audit\n\nAn audit could be carried out on a reasonable number of people being treated for chronic hepatitis B, for audit purposes, for example, patients seen over 6 months, excluding people with chronic hepatitis B who are known to be co-infected with hepatitis C, hepatitis D or HIV.\n\n# Measures that could be used as a basis for an audit\n\nThe measures that could be used in an audit of adefovir dipivoxil and peginterferon alfa-2a for chronic hepatitis B are as follows.\n\nCriterion\n\nStandard\n\nException\n\nDefinition of terms\n\nA. For an adult with chronic hepatitis B (HBeAg-positive or -negative), peginterferon alfa-2a is considered as an option for initial treatment in accordance with its licensed indications\n\n% of adults with chronic hepatitis B (HBeAg-positive or -negative)\n\nA. The person has a contra-indication to peginter-feron alfa-2a\n\nClinicians will need to agree locally on how consideration of the options for treatment is documented for audit purposes.\n\nA contraindication is decompensated cirrhosis of the liver. See the 'Summary of product characteristics' for details of contraindications.\n\n. For an adult with chronic hepatitis B (HBeAg-positive or -negative), adefovir dipivoxil is considered as an option for treatment, in accordance with its licensed indications, if:\n\na. treatment with interferon alfa or peginterferon alfa-2a has been unsuccessful or\n\nb. a relapse occurs after successful initial treatment or\n\nc. interferon alfa or peginterferon alfa-2a is poorly tolerated or contraindicated\n\n% of adults with chronic hepatitis B (HBeAg-positive or -negative) who meet any of 2a–2c\n\nB. The person has a contra-indication to adefovir dipivoxil\n\nClinicians will need to agree locally on the sources of evidence for 2a–c and how consideration of the options for treatment is documented for audit purposes.\n\n'Interferon alfa' includes interferon alfa-2a or -2b.\n\n'Successful' treatment is considered to be treatment that leads to HBeAG seroconversion (in the case of HBeAg-positive disease) or an adequate reduction in viral load (in the case of HBeAg-negative disease). Clinicians will need to agree locally on how success of treatment is assessed, and how relapse after initial treatment and tolerance to adverse effects are documented for audit purposes.\n\nSee the 'Summary of product characteristics' for details of contraindications.\n\n. Adefovir dipivoxil is given before treatment with lamivudine\n\n% of people with chronic hepatitis B for whom initial treatment options are being considered\n\nC. There is a clinical justification for treating with adefovir dipivoxil before lamivudine\n\nClinicians will need to agree locally on clinical justifications for treating people with chronic hepatitis B with adefovir dipivoxil before lamivudine.\n\n. Adefovir dipivoxil is used either alone or in combination with lamivudine in either of the following circumstances:\n\na. treatment with lamivudine has resulted in viral resistance or\n\nb. lamivudine resistance is likely to occur rapidly and development of lamivudine resistance is likely to have an adverse outcome\n\n% of the people with chronic hepatitis B for whom adefovir dipivoxil is being prescribed\n\nNone\n\nClinicians will need to agree locally on how treatment with lamivudine resulting in viral resistance and adverse outcomes are documented for audit purposes.\n\nAn example of lamivudine resistance being likely to occur rapidly is the presence of highly replicative hepatitis B disease.\n\nAn example of an adverse outcome is a flare of the infection that is likely to precipitate decompensated liver disease.\n\n. Drug treatment with peginterferon alfa-2a and adefovir dipivoxil is initiated by an appropriately qualified healthcare professional with expertise in the management of viral hepatitis\n\n% of people with chronic hepatitis B for whom peginterferon alfa-2a or adefovir dipivoxil is prescribed\n\nNone\n\nClinicians will need to agree locally on the definition of an appropriately qualified healthcare professional with expertise in the management of viral hepatitis, for audit purposes.\n\n# Calculation of compliance\n\nCompliance (%) with each measure described in the table above is calculated as follows.\n\nNumber of patients whose care is consistent with the criterion plus number of patients who meet any exception listed\n\n\n\nx 100\n\nNumber of patients to whom the measure applies\n\nClinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.", 'Changes after publication': 'March 2014: implementation section updated to clarify that adefovir dipivoxil and peginterferon alfa-2a are recommended as options for treating chronic hepatitis B. Additional minor maintenance update also carried out.\n\nJune 2013: Recommendations 1.2–1.4 replaced by recommendations 1.5.13–1.5.15 in Hepatitis B (chronic): diagnosis and management of chronic hepatitis B in children, young people and adults (NICE clinical guideline 165).\n\nMarch 2012: minor maintenance', 'About this guidance': 'NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales.\n\nThis guidance was developed using the NICE multiple technology appraisal process.\n\nIt has been updated by NICE clinical guideline 165 (published June 2013) and incorporated into the NICE pathway on hepatitis B (chronic) in the antiviral treatment in adults with chronic hepatitis B path along with other related guidance and products.\n\nWe have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.'}	https://www.nice.org.uk/guidance/ta96	Evidence-based recommendations on adefovir dipivoxil (Hepsera) and peginterferon alfa-2a (Pegasys) for treating chronic hepatitis B in adults.
4e6018592acb9d59d54d9df340529b1a10dd70c8	nice	Image-guided vacuum-assisted excision biopsy of benign breast lesions	Image-guided vacuum-assisted excision biopsy of benign breast lesions # Guidance Current evidence on the safety and efficacy of image-guided vacuum-assisted excision biopsy of benign breast lesions appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. Clinicians wishing to perform this procedure should undergo training as recommended by the Royal College of Radiologists in 'Ultrasound training recommendations for medical and surgical specialties'.# The procedure # Indications Image-guided vacuum-assisted core biopsy has been regularly used for gathering samples of tissue in women with breast lesions suspicious of breast cancer, or when histological evidence of a benign lesion is required. This procedure can also be used to remove benign breast lesions such as fibroadenomas. This can reduce the need for open surgical biopsy or excision. Diagnosis of benign breast disease is usually done by clinical examination, imaging and fine needle biopsy; this is known as the triple test. Women who have negative results for malignancy in all three tests may choose to have benign lumps removed. # Outline of the procedure The procedure involves the use of a needle probe device with vacuum suction to remove breast tissue under imaging guidance (commonly ultrasound). The aim of the procedure is to continue using the biopsy device until the lesion visible on imaging has been removed. A small incision is made in the breast and an 8- or 11-gauge probe is inserted through the lesion. Small amounts of tissue are aspirated and the probe is withdrawn further into the lesion and the process repeated. When the device has been removed the site of incision is compressed for a short time. The procedure takes between 13 and 60 minutes, depending on the size of lesion being removed. The procedure can be performed on an outpatient basis under local anaesthesia. # Efficacy Complete removal was achieved in between 22% (21/95) and 98% (121/124) of lesions. The success rate may depend on the gauge of the probe used and the size of the lesion to be removed (these are often dependent variables). The accuracy of determining complete removal may depend on the quality of the imaging technique used. In one case series, 23% (3/13) of patients with incompletely excised lesions after vacuum-assisted biopsy had subsequent open surgery excision. For more details, refer to the Sources of evidence. # Safety The most frequent complication of this procedure was haematoma. This complication was recorded in 13% (24/186) of patients in one case series, but none of these haematomas were classified as serious. In another study of 20 patients, no clinically problematic haematomas were reported. In one large case series, 39% (73/186) of patients complained of mild postoperative pain, and 4% (8/186) of moderate pain. No patients reported severe pain. Bleeding during the procedure occurred in 4% (2/56) of patients in one case series, and in 2% (3/186) in another. However, all three latter cases resolved with little or no intervention. For more details, refer to the Sources of evidence. The Specialist Advisors noted that complications include haemorrhage, haematoma formation, vasovagal episodes and failure to excise the correct area. In addition, wound infection is a possible problem. # Other comments It was noted that, despite prior biopsy, patients may occasionally be found to have a malignant cancer. It was noted that benign lesions such as fibroadenomas may sometimes recur after this procedure.# Further information The NHS Breast Screening Programme has produced guidelines entitled 'Clinical guidelines for breast cancer screening assessment'. Andrew DillonChief ExecutiveFebruary 2006 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of image-guided vacuum-assisted excision biopsy of benign breast lesions', February 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of image-guided vacuum-assisted excision biopsy of benign breast lesions appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians wishing to perform this procedure should undergo training as recommended by the Royal College of Radiologists in 'Ultrasound training recommendations for medical and surgical specialties'.", 'The procedure': '# Indications\n\nImage-guided vacuum-assisted core biopsy has been regularly used for gathering samples of tissue in women with breast lesions suspicious of breast cancer, or when histological evidence of a benign lesion is required. This procedure can also be used to remove benign breast lesions such as fibroadenomas. This can reduce the need for open surgical biopsy or excision.\n\nDiagnosis of benign breast disease is usually done by clinical examination, imaging and fine needle biopsy; this is known as the triple test. Women who have negative results for malignancy in all three tests may choose to have benign lumps removed.\n\n# Outline of the procedure\n\nThe procedure involves the use of a needle probe device with vacuum suction to remove breast tissue under imaging guidance (commonly ultrasound). The aim of the procedure is to continue using the biopsy device until the lesion visible on imaging has been removed. A small incision is made in the breast and an 8- or 11-gauge probe is inserted through the lesion. Small amounts of tissue are aspirated and the probe is withdrawn further into the lesion and the process repeated. When the device has been removed the site of incision is compressed for a short time. The procedure takes between 13 and 60 minutes, depending on the size of lesion being removed. The procedure can be performed on an outpatient basis under local anaesthesia.\n\n# Efficacy\n\nComplete removal was achieved in between 22% (21/95) and 98% (121/124) of lesions. The success rate may depend on the gauge of the probe used and the size of the lesion to be removed (these are often dependent variables). The accuracy of determining complete removal may depend on the quality of the imaging technique used.\n\nIn one case series, 23% (3/13) of patients with incompletely excised lesions after vacuum-assisted biopsy had subsequent open surgery excision. For more details, refer to the Sources of evidence.\n\n# Safety\n\nThe most frequent complication of this procedure was haematoma. This complication was recorded in 13% (24/186) of patients in one case series, but none of these haematomas were classified as serious. In another study of 20 patients, no clinically problematic haematomas were reported.\n\nIn one large case series, 39% (73/186) of patients complained of mild postoperative pain, and 4% (8/186) of moderate pain. No patients reported severe pain.\n\nBleeding during the procedure occurred in 4% (2/56) of patients in one case series, and in 2% (3/186) in another. However, all three latter cases resolved with little or no intervention. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that complications include haemorrhage, haematoma formation, vasovagal episodes and failure to excise the correct area. In addition, wound infection is a possible problem.\n\n# Other comments\n\nIt was noted that, despite prior biopsy, patients may occasionally be found to have a malignant cancer.\n\nIt was noted that benign lesions such as fibroadenomas may sometimes recur after this procedure.', 'Further information': "The NHS Breast Screening Programme has produced guidelines entitled 'Clinical guidelines for breast cancer screening assessment'.\n\nAndrew DillonChief ExecutiveFebruary 2006\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of image-guided vacuum-assisted excision biopsy of benign breast lesions', February 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg156
dd28e012b5486b629b2bdd52493fc0ee8f5cb2f4	nice	Photodynamic therapy for non-melanoma skin tumours (including premalignant and primary non-metastatic skin lesions)	Photodynamic therapy for non-melanoma skin tumours (including premalignant and primary non-metastatic skin lesions) # Guidance Current evidence suggests that there are no major safety concerns associated with photodynamic therapy for non-melanoma skin tumours (including premalignant and primary non-metastatic skin lesions). Evidence of efficacy of this procedure for the treatment of basal cell carcinoma, Bowen's disease and actinic (solar) keratosis is adequate to support its use for these conditions, provided that the normal arrangements are in place for consent, audit and clinical governance. Evidence is limited on the efficacy of this procedure for the treatment of invasive squamous cell carcinoma. Recurrence rates are high and there is a risk of metastasis. Clinicians should ensure that patients understand these risks and that retreatment may be necessary. In addition, use of the Institute's information for the public is recommended.# The procedure # Indications Non-melanoma skin tumours include basal cell carcinoma, squamous cell carcinoma, Bowen's disease and actinic (or solar) keratosis. Basal cell carcinoma is the most common form of skin cancer. It is generally a slow-growing, locally invasive epidermal skin tumour that rarely spreads to other distant parts of the body. Although it is not usually life threatening, the tumour can cause extensive tissue destruction if it is not treated adequately. Squamous cell carcinoma is the second most common type of skin cancer in the UK. It arises from cells in the epidermis and spreads into the surrounding skin. It can also spread to nearby lymph nodes and may be life threatening in rare cases. Bowen's disease is an early form of non-melanoma skin cancer. If untreated, it can progress to invasive squamous cell carcinoma. Actinic keratoses are small lumps of hard skin that are usually harmless but have the potential to develop into squamous cell carcinoma. Current treatments for basal cell carcinoma include topical chemotherapy, curettage, surgical excision, cryotherapy and radiotherapy. Squamous cell carcinoma is usually removed surgically. Bowen's disease and actinic keratoses are usually treated with curettage, cryotherapy or topical chemotherapy. # Outline of the procedure In photodynamic therapy (PDT), the lesion is prepared by removing overlying crust and scale. A photosensitising agent is applied to the lesion and a margin of surrounding skin. The lesion is illuminated by light of an appropriate wavelength to activate the photosensitiser, producing targeted tumour destruction. Occasionally, the photosensitising agent may be given intravenously. More than one lesion may be treated in a session and the treatment can be repeated. # Efficacy One randomised controlled trial (RCT) of patients with basal cell carcinoma reported that there was no statistically significant difference in lesion clearance between PDT and surgery (91% and 98% of patients, respectively). Another RCT reported that 25% (11/44) of patients had a positive biopsy at 12 months after PDT compared with 15% (6/39) of patients after cryotherapy (p > 0.05). Both of these studies reported statistically significantly better cosmetic outcomes after PDT than after the comparator. Two RCTs compared PDT and cryotherapy in patients with actinic keratosis. One reported a similar lesion clearance rate for PDT and cryotherapy (69% and 75% , respectively) whereas the other reported a clearance rate of 91% (267/295) for lesions treated with PDT at 3 months, compared with 68% (278/407) of lesions treated with cryotherapy (p < 0.001). Both studies reported that cosmetic outcomes were good or excellent in a significantly higher proportion of patients after PDT. A case series of 59 patients with basal cell carcinoma reported that the overall cure rate was 79% (277/350) of lesions after a mean follow-up of 35 months. For more details refer to the Sources of evidence. The Specialist Advisors stated that there were some concerns about recurrence rates and that the treatment may be more appropriate for large, superficial lesions of Bowen's disease, actinic keratosis and basal cell carcinoma, especially where there are multiple lesions and where repair would otherwise require extensive surgery. # Safety Adverse events were mainly transient local reactions. Three studies reported that the total rate of adverse events ranged from 43% (44/102) to 90% (38/42) of patients. The most common complication was a burning sensation of the skin, and this affected between 31% (16/52) and 64% (27/42) of patients. Two studies reported ulceration rates of 0% (0/20) and 12% (5/42), respectively. One large case series reported minor pigmentary changes and superficial scarring each in 2% (10/483) of lesions. Other adverse events included pain, erythema, crusting, itching, oedema and blisters. For more details refer to the sources of evidence. The Specialist Advisors stated that the procedure is generally safe and well tolerated. It is theoretically possible that the treatment could induce carcinogenicity but this is likely to be a low risk. # Other comments It was noted that there is a large variety of benign skin tumours and the guidance refers only to those mentioned in section 2.1.1. It was noted that a variety of agents and treatments are used. It was also noted that results may vary depending on the conditions being treated, and that a Cochrane review is being developed on photodynamic therapy for localised squamous cell carcinoma of the skin and its precursors. Andrew DillonChief ExecutiveFebruary 2006# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of photodynamic therapy for non-melanoma skin tumours (including premalignant and primary non-metastatic skin lesions', April 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence suggests that there are no major safety concerns associated with photodynamic therapy for non-melanoma skin tumours (including premalignant and primary non-metastatic skin lesions).\n\nEvidence of efficacy of this procedure for the treatment of basal cell carcinoma, Bowen's disease and actinic (solar) keratosis is adequate to support its use for these conditions, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nEvidence is limited on the efficacy of this procedure for the treatment of invasive squamous cell carcinoma. Recurrence rates are high and there is a risk of metastasis. Clinicians should ensure that patients understand these risks and that retreatment may be necessary. In addition, use of the Institute's information for the public is recommended.", 'The procedure': "# Indications\n\nNon-melanoma skin tumours include basal cell carcinoma, squamous cell carcinoma, Bowen's disease and actinic (or solar) keratosis.\n\nBasal cell carcinoma is the most common form of skin cancer. It is generally a slow-growing, locally invasive epidermal skin tumour that rarely spreads to other distant parts of the body. Although it is not usually life threatening, the tumour can cause extensive tissue destruction if it is not treated adequately. Squamous cell carcinoma is the second most common type of skin cancer in the UK. It arises from cells in the epidermis and spreads into the surrounding skin. It can also spread to nearby lymph nodes and may be life threatening in rare cases. Bowen's disease is an early form of non-melanoma skin cancer. If untreated, it can progress to invasive squamous cell carcinoma. Actinic keratoses are small lumps of hard skin that are usually harmless but have the potential to develop into squamous cell carcinoma.\n\nCurrent treatments for basal cell carcinoma include topical chemotherapy, curettage, surgical excision, cryotherapy and radiotherapy. Squamous cell carcinoma is usually removed surgically. Bowen's disease and actinic keratoses are usually treated with curettage, cryotherapy or topical chemotherapy.\n\n# Outline of the procedure\n\nIn photodynamic therapy (PDT), the lesion is prepared by removing overlying crust and scale. A photosensitising agent is applied to the lesion and a margin of surrounding skin. The lesion is illuminated by light of an appropriate wavelength to activate the photosensitiser, producing targeted tumour destruction. Occasionally, the photosensitising agent may be given intravenously. More than one lesion may be treated in a session and the treatment can be repeated.\n\n# Efficacy\n\nOne randomised controlled trial (RCT) of patients with basal cell carcinoma reported that there was no statistically significant difference in lesion clearance between PDT and surgery (91% [48/53] and 98% [51/52] of patients, respectively). Another RCT reported that 25% (11/44) of patients had a positive biopsy at 12 months after PDT compared with 15% (6/39) of patients after cryotherapy (p > 0.05). Both of these studies reported statistically significantly better cosmetic outcomes after PDT than after the comparator.\n\nTwo RCTs compared PDT and cryotherapy in patients with actinic keratosis. One reported a similar lesion clearance rate for PDT and cryotherapy (69% [252/367] and 75% [250/332], respectively) whereas the other reported a clearance rate of 91% (267/295) for lesions treated with PDT at 3 months, compared with 68% (278/407) of lesions treated with cryotherapy (p < 0.001). Both studies reported that cosmetic outcomes were good or excellent in a significantly higher proportion of patients after PDT.\n\nA case series of 59 patients with basal cell carcinoma reported that the overall cure rate was 79% (277/350) of lesions after a mean follow-up of 35 months. For more details refer to the Sources of evidence.\n\nThe Specialist Advisors stated that there were some concerns about recurrence rates and that the treatment may be more appropriate for large, superficial lesions of Bowen's disease, actinic keratosis and basal cell carcinoma, especially where there are multiple lesions and where repair would otherwise require extensive surgery.\n\n# Safety\n\nAdverse events were mainly transient local reactions. Three studies reported that the total rate of adverse events ranged from 43% (44/102) to 90% (38/42) of patients. The most common complication was a burning sensation of the skin, and this affected between 31% (16/52) and 64% (27/42) of patients. Two studies reported ulceration rates of 0% (0/20) and 12% (5/42), respectively. One large case series reported minor pigmentary changes and superficial scarring each in 2% (10/483) of lesions. Other adverse events included pain, erythema, crusting, itching, oedema and blisters. For more details refer to the sources of evidence.\n\nThe Specialist Advisors stated that the procedure is generally safe and well tolerated. It is theoretically possible that the treatment could induce carcinogenicity but this is likely to be a low risk.\n\n# Other comments\n\nIt was noted that there is a large variety of benign skin tumours and the guidance refers only to those mentioned in section 2.1.1.\n\nIt was noted that a variety of agents and treatments are used.\n\nIt was also noted that results may vary depending on the conditions being treated, and that a Cochrane review is being developed on photodynamic therapy for localised squamous cell carcinoma of the skin and its precursors.\n\nAndrew DillonChief ExecutiveFebruary 2006", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of photodynamic therapy for non-melanoma skin tumours (including premalignant and primary non-metastatic skin lesions', April 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg155
016154a045328bd7b1fbe3bf7ef4150360519858	nice	Laparoscopic partial nephrectomy	Laparoscopic partial nephrectomy # Guidance Current evidence on laparoscopic partial nephrectomy suggests that it is safe and efficacious when undertaken by surgeons with special expertise in this technique. Surgeons undertaking laparoscopic partial nephrectomy should have specific training and regular experience in laparoscopic renal surgery. Clinicians wishing to undertake this procedure should ensure that patients fully understand the risks, including that of serious haemorrhage. In addition, use of the Institute's information for the public is recommended. Clinicians should audit and review their results. The British Association of Urological Surgeons runs a cancer registry, and clinicians are encouraged to enter all patients undergoing laparoscopic partial nephrectomy onto this database.# The procedure # Indications Indications for laparoscopic partial nephrectomy include: a solid renal tumour in a patient with a solitary kidney or compromised contralateral kidney; bilateral renal tumours; and small localised renal tumours in patients with a normal contralateral kidney. Most solid renal tumours are renal cell carcinomas but a small proportion of them are benign tumours, such as oncocytomas. The standard treatment for renal tumours is open partial nephrectomy. Some small tumours may not be suitable for laparoscopic partial nephrectomy because of their position (centrally located lesions are more difficult to remove than peripheral lesions). # Outline of the procedure A laparoscopic partial nephrectomy is performed under general anaesthetic, using a transperitoneal or retroperitoneal approach. In the transperitoneal approach, the abdomen is insufflated with carbon dioxide and three or four small abdominal incisions are made. In the retroperitoneal approach, a small incision is made in the back and a dissecting balloon is inserted to create a retroperitoneal space. After insufflation with carbon dioxide, two or three additional small incisions are made in the back. The renal vessels are identified and either controlled using vessel loops or clamped, and the kidney is mobilised to allow exposure of the lesion. A laparoscopic ultrasound probe may be used to determine the line of incision and depth of tumour involvement. The specimen is enclosed in a bag and retrieved through an expanded port. Hand-assisted laparoscopic partial nephrectomy allows the surgeon to place one hand in the abdomen while maintaining the pneumoperitoneum required for laparoscopy. An additional small incision is made that is just large enough for the surgeon's hand, and an airtight 'sleeve' device is used to form a seal around the incision. # Efficacy One non-randomised comparative study of 200 patients reported a median hospital stay of 2 days for laparoscopic partial nephrectomy compared with 5 days for open partial nephrectomy (p < 0.001). A second non-randomised comparative study, which involved 49 patients, reported a mean hospital stay of 3 days for the laparoscopic procedure compared with 6 days for open surgery (p < 0.0002). The first of these studies also reported a significantly shorter median convalescence time for laparoscopic partial nephrectomy compared with open partial nephrectomy (4 weeks versus 6 weeks, p < 0.001). In one non-randomised comparative study, positive surgical margins (with tumour involvement) were reported after 3% (3/100) of laparoscopic partial nephrectomies compared with 0% (0/100) of open partial nephrectomies. In a second non-randomised comparative study, positive surgical margins were reported in 0% (0/27) of laparoscopic procedures and 5% (1/22) of open procedures. Two case series reported positive surgical margins in 3% (1/37 and 3/100) of cases. Three studies reported tumour recurrence rates of 0% (0/100), 0% (0/79) and 4% (2/48) after mean follow-up periods of 15 months, 20 months and 38 months, respectively. For more details, refer to the Sources of evidence. The Specialist Advisors noted concern about the possibility of incomplete cancer clearance. # Safety Six studies reported urine leakage as a complication, affecting between 2% (2/100) and 9% (5/53) of patients. In three studies, the rate of postoperative haemorrhage was 2% (4/200, 2/100 and 1/53 of patients), and the rate of intraoperative haemorrhage ranged from 3% (3/100) to 8% (4/53). Other complications included renal failure; damage to the ureter, bowel and blood vessels; and urinary tract infection. For more details, refer to the sources of evidence. The main safety concerns listed by the Specialist Advisors were intraoperative and postoperative bleeding, and urine leak. # Other comments It was noted that the published evidence came from highly specialised units experienced in laparoscopic renal surgery, where clinicians have undertaken a large number of laparoscopic partial nephrectomies. Andrew DillonChief ExecutiveJanuary 2006# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of laparoscopic partial nephrectomy', April 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on laparoscopic partial nephrectomy suggests that it is safe and efficacious when undertaken by surgeons with special expertise in this technique. Surgeons undertaking laparoscopic partial nephrectomy should have specific training and regular experience in laparoscopic renal surgery.\n\nClinicians wishing to undertake this procedure should ensure that patients fully understand the risks, including that of serious haemorrhage. In addition, use of the Institute's information for the public is recommended.\n\nClinicians should audit and review their results. The British Association of Urological Surgeons runs a cancer registry, and clinicians are encouraged to enter all patients undergoing laparoscopic partial nephrectomy onto this database.", 'The procedure': "# Indications\n\nIndications for laparoscopic partial nephrectomy include: a solid renal tumour in a patient with a solitary kidney or compromised contralateral kidney; bilateral renal tumours; and small localised renal tumours in patients with a normal contralateral kidney. Most solid renal tumours are renal cell carcinomas but a small proportion of them are benign tumours, such as oncocytomas. The standard treatment for renal tumours is open partial nephrectomy.\n\nSome small tumours may not be suitable for laparoscopic partial nephrectomy because of their position (centrally located lesions are more difficult to remove than peripheral lesions).\n\n# Outline of the procedure\n\nA laparoscopic partial nephrectomy is performed under general anaesthetic, using a transperitoneal or retroperitoneal approach. In the transperitoneal approach, the abdomen is insufflated with carbon dioxide and three or four small abdominal incisions are made. In the retroperitoneal approach, a small incision is made in the back and a dissecting balloon is inserted to create a retroperitoneal space. After insufflation with carbon dioxide, two or three additional small incisions are made in the back. The renal vessels are identified and either controlled using vessel loops or clamped, and the kidney is mobilised to allow exposure of the lesion. A laparoscopic ultrasound probe may be used to determine the line of incision and depth of tumour involvement. The specimen is enclosed in a bag and retrieved through an expanded port.\n\nHand-assisted laparoscopic partial nephrectomy allows the surgeon to place one hand in the abdomen while maintaining the pneumoperitoneum required for laparoscopy. An additional small incision is made that is just large enough for the surgeon's hand, and an airtight 'sleeve' device is used to form a seal around the incision.\n\n# Efficacy\n\nOne non-randomised comparative study of 200 patients reported a median hospital stay of 2 days for laparoscopic partial nephrectomy compared with 5 days for open partial nephrectomy (p < 0.001). A second non-randomised comparative study, which involved 49 patients, reported a mean hospital stay of 3 days for the laparoscopic procedure compared with 6 days for open surgery (p < 0.0002). The first of these studies also reported a significantly shorter median convalescence time for laparoscopic partial nephrectomy compared with open partial nephrectomy (4 weeks versus 6 weeks, p < 0.001).\n\nIn one non-randomised comparative study, positive surgical margins (with tumour involvement) were reported after 3% (3/100) of laparoscopic partial nephrectomies compared with 0% (0/100) of open partial nephrectomies. In a second non-randomised comparative study, positive surgical margins were reported in 0% (0/27) of laparoscopic procedures and 5% (1/22) of open procedures. Two case series reported positive surgical margins in 3% (1/37 and 3/100) of cases.\n\nThree studies reported tumour recurrence rates of 0% (0/100), 0% (0/79) and 4% (2/48) after mean follow-up periods of 15 months, 20 months and 38 months, respectively. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted concern about the possibility of incomplete cancer clearance.\n\n# Safety\n\nSix studies reported urine leakage as a complication, affecting between 2% (2/100) and 9% (5/53) of patients. In three studies, the rate of postoperative haemorrhage was 2% (4/200, 2/100 and 1/53 of patients), and the rate of intraoperative haemorrhage ranged from 3% (3/100) to 8% (4/53). Other complications included renal failure; damage to the ureter, bowel and blood vessels; and urinary tract infection. For more details, refer to the sources of evidence.\n\nThe main safety concerns listed by the Specialist Advisors were intraoperative and postoperative bleeding, and urine leak.\n\n# Other comments\n\nIt was noted that the published evidence came from highly specialised units experienced in laparoscopic renal surgery, where clinicians have undertaken a large number of laparoscopic partial nephrectomies.\n\nAndrew DillonChief ExecutiveJanuary 2006", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of laparoscopic partial nephrectomy', April 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg151
4f5d3b1653c98579b6b0890030ca96914b6824f5	nice	Foker technique for long-gap oesophageal atresia	Foker technique for long-gap oesophageal atresia # Guidance Current evidence on the safety and efficacy of the Foker technique for long-gap oesophageal atresia is limited but appears adequate to support the use of the procedure in the context of this rare and serious condition, provided that normal arrangements are in place for consent, audit and clinical governance. Clinicians wishing to undertake the Foker technique should ensure that parents understand the implications of the condition and know that secondary interventions may be necessary. In addition, use of the Institute's information for the public is recommended. This procedure should be undertaken only in specialist paediatric surgical units by surgeons specifically trained in this technique. Clinicians should audit and review their results. Publication of further information about the Foker technique and its outcomes may be useful.# The procedure # Indications Oesophageal atresia is a congenital condition in which there is a break in the continuity of the oesophagus between the mouth and stomach. In some patients, both the proximal and the distal ends of the oesophagus end in blind pouches; more commonly, one or both ends of the oesophagus are attached to the trachea, forming tracheo-oesophageal fistulae. Saliva and milk enter the lungs after pooling in the upper oesophagus or passing though a tracheo-oesophageal fistula, resulting in episodes of choking, coughing and cyanosis. If untreated, oesophageal atresia leads to death from aspiration pneumonia or malnutrition. The vast majority of patients are treated by surgical division of the fistula and primary anastomosis of the oesophagus, to allow normal swallowing. The definition of long-gap atresia varies, but generally it means the gap is greater than 3–3.5 cm. With long-gap atresia, any direct anastomosis is placed under significant tension. Therefore, any fistula is divided, and a gastrostomy is sited to enable enteral feeding. Repair is delayed for up to 3 months to allow the upper and lower pouches to elongate and hypertrophy, with the intention that anastomosis will then be possible. If it is not possible, alternative surgical approaches include pulling the stomach partially up into the thorax, or using a length of colon to join the oesophageal ends. # Outline of the procedure Using a transthoracic extrapleural approach, the fistula or fistulae are divided and oversewn. The oesophageal pouches are exposed and traction sutures are placed in the ends, brought out through the skin and fixed with silastic buttons. Traction is applied to the sutures, which stimulates elongation of the oesophagus by 1–2 mm per day. Once the ends of the oesophagus have come together, or are in close proximity, a primary anastomosis is performed. After the repair, the patient may be kept sedated and ventilated for a number of days to allow the anastomosis to heal. Oesophageal balloon dilatation may be performed if required. # Efficacy Reported clinical outcomes varied considerably between studies, and were often qualitative only. One case series reported 70 infants with oesophageal atresia treated by primary repair: 10 of the patients had long-gap atresia and four of these were treated with the Foker technique. All four patients were eating excellently or satisfactorily at a mean follow-up of 8.8 years. After treatment, all 10 of the infants with long-gap atresia had gastro-oesophageal reflux requiring fundoplication. A second case series described 23 cases in which the babies were treated with external traction (atresia length ranged from 3.7 to 10 cm). A primary anastomosis was achieved in all cases. Another case series reported that 67% (2/3) of patients achieved full oral feeding at up to 4 months after treatment with the Foker technique. Another found that 50% (1/2) of patients were eating solids normally at 1 year, and 50% (1/2) still required a gastric tube for feeding. The rate of successful anastomosis varied between studies from 100% (4/4 and 2/2) to 33% (1/3). For more details, refer to the Sources of evidence. # Safety Disruption of sutures during the traction stage of the procedure occurred in 25% (3/12) of patients with long-gap atresia across all the studies identified, usually requiring the anastomosis to be performed under greater tension than intended. No deaths were reported that were directly related to repair of the oesophageal atresia. The Specialist Advisors noted adverse events including stricture formation and gastro-oesophageal reflux. They also noted other possible adverse events including anastomotic leak, suture disruption during the period of traction, fistulae, gastric emptying problems and difficulties in swallowing. # Other comments Long-gap oesophageal atresia is often associated with multiple abnormalities, and mortality after the Foker technique is often related to these conditions rather than to the operation. Andrew DillonChief ExecutiveJanuary 2006# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of the Foker technique for long-gap oesophageal atresia', May 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of the Foker technique for long-gap oesophageal atresia is limited but appears adequate to support the use of the procedure in the context of this rare and serious condition, provided that normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians wishing to undertake the Foker technique should ensure that parents understand the implications of the condition and know that secondary interventions may be necessary. In addition, use of the Institute's information for the public is recommended.\n\nThis procedure should be undertaken only in specialist paediatric surgical units by surgeons specifically trained in this technique.\n\nClinicians should audit and review their results. Publication of further information about the Foker technique and its outcomes may be useful.", 'The procedure': '# Indications\n\nOesophageal atresia is a congenital condition in which there is a break in the continuity of the oesophagus between the mouth and stomach. In some patients, both the proximal and the distal ends of the oesophagus end in blind pouches; more commonly, one or both ends of the oesophagus are attached to the trachea, forming tracheo-oesophageal fistulae. Saliva and milk enter the lungs after pooling in the upper oesophagus or passing though a tracheo-oesophageal fistula, resulting in episodes of choking, coughing and cyanosis. If untreated, oesophageal atresia leads to death from aspiration pneumonia or malnutrition.\n\nThe vast majority of patients are treated by surgical division of the fistula and primary anastomosis of the oesophagus, to allow normal swallowing.\n\nThe definition of long-gap atresia varies, but generally it means the gap is greater than 3–3.5 cm. With long-gap atresia, any direct anastomosis is placed under significant tension. Therefore, any fistula is divided, and a gastrostomy is sited to enable enteral feeding. Repair is delayed for up to 3 months to allow the upper and lower pouches to elongate and hypertrophy, with the intention that anastomosis will then be possible. If it is not possible, alternative surgical approaches include pulling the stomach partially up into the thorax, or using a length of colon to join the oesophageal ends.\n\n# Outline of the procedure\n\nUsing a transthoracic extrapleural approach, the fistula or fistulae are divided and oversewn. The oesophageal pouches are exposed and traction sutures are placed in the ends, brought out through the skin and fixed with silastic buttons. Traction is applied to the sutures, which stimulates elongation of the oesophagus by 1–2 mm per day. Once the ends of the oesophagus have come together, or are in close proximity, a primary anastomosis is performed. After the repair, the patient may be kept sedated and ventilated for a number of days to allow the anastomosis to heal. Oesophageal balloon dilatation may be performed if required.\n\n# Efficacy\n\nReported clinical outcomes varied considerably between studies, and were often qualitative only. One case series reported 70 infants with oesophageal atresia treated by primary repair: 10 of the patients had long-gap atresia and four of these were treated with the Foker technique. All four patients were eating excellently or satisfactorily at a mean follow-up of 8.8 years. After treatment, all 10 of the infants with long-gap atresia had gastro-oesophageal reflux requiring fundoplication. A second case series described 23 cases in which the babies were treated with external traction (atresia length ranged from 3.7 to 10 cm). A primary anastomosis was achieved in all cases.\n\nAnother case series reported that 67% (2/3) of patients achieved full oral feeding at up to 4 months after treatment with the Foker technique. Another found that 50% (1/2) of patients were eating solids normally at 1 year, and 50% (1/2) still required a gastric tube for feeding. The rate of successful anastomosis varied between studies from 100% (4/4 and 2/2) to 33% (1/3). For more details, refer to the Sources of evidence.\n\n# Safety\n\nDisruption of sutures during the traction stage of the procedure occurred in 25% (3/12) of patients with long-gap atresia across all the studies identified, usually requiring the anastomosis to be performed under greater tension than intended. No deaths were reported that were directly related to repair of the oesophageal atresia.\n\nThe Specialist Advisors noted adverse events including stricture formation and gastro-oesophageal reflux. They also noted other possible adverse events including anastomotic leak, suture disruption during the period of traction, fistulae, gastric emptying problems and difficulties in swallowing.\n\n# Other comments\n\nLong-gap oesophageal atresia is often associated with multiple abnormalities, and mortality after the Foker technique is often related to these conditions rather than to the operation.\n\nAndrew DillonChief ExecutiveJanuary 2006', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of the Foker technique for long-gap oesophageal atresia', May 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2006. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg153
b4e7625aecf6522c7f0d4090b1c48dde9fab276b	nice	Endoscopic axillary lymph node retrieval for breast cancer	Endoscopic axillary lymph node retrieval for breast cancer # Guidance Current evidence on the safety and efficacy of endoscopic axillary lymph node retrieval for breast cancer does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake endoscopic axillary lymph node retrieval should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. In addition, use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having endoscopic axillary lymph node retrieval for breast cancer. This procedure should only be undertaken by surgeons skilled in endoscopic techniques.# The procedure # Indications Axillary clearance has been used as part of surgery for breast cancer. Biopsy of lymph node tissue helps in the staging of breast cancer, providing prognostic information and identifying patients who will benefit from systemic therapy. Traditionally, surgeons remove lymph nodes for staging through an incision in the axillary skin under direct vision. However, this procedure may have side effects, including wound infection and lymphoedema. There are two surgical alternatives that are standard practice. The first involves clearance to level one, two or three of the axilla, taking up to 20 lymph nodes, which provides very accurate diagnostic information. The second requires sampling of a minimum of four lymph nodes, which causes less morbidity but provides only qualitative rather than quantitative information about the status of the axillary basin of lymph nodes. A new procedure is sentinel node mapping, which requires specific training in the use of imaging. Endoscopic techniques, sometimes combined with liposuction, have been developed as a less invasive approach to removing lymph nodes for diagnosis. # Outline of the procedure In endoscopic axillary lymph node retrieval, very small incisions are made in the axillary skin and nodes are removed using an endoscope and special instruments. The patient is placed in a supine position under general anaesthesia. Liposuction is used to remove excess axillary fat. An endoscope is inserted through the incision used for liposuction, and trocars are introduced through two additional small incisions. Fibrous tracts and small lymph and blood vessels are coagulated and cut, and lymph nodes are freed and removed. Following a saline rinse of the surgical field, the incisions are sutured. Drains are not normally required. # Efficacy Conversion to open surgery was reported in 8% (4/53) of operations in a historically controlled study. In a large case series, only 2% (2/100) of operations were converted to open surgery. In one randomised controlled trial, the operative time for endoscopic axillary lymph node retrieval was found to be significantly longer than for open surgery (mean time 61 and 33 minutes, respectively). One quasi-randomised study found good shoulder–arm mobility at 7 days postoperatively, with more than 90% mobility being achieved after either endoscopic axillary lymph node retrieval or open surgery. Only 18% (7/40) of patients who had endoscopic axillary lymph node retrieval reported pain on the first postoperative day, compared with 33% (13/40) of patients who had open surgery. One small randomised controlled trial found that all ten patients reported no pain at 3 days after endoscopic axillary lymph node retrieval. Length of hospital stay after endoscopic axillary lymph node retrieval varied from 2.5 days to 9 days, although one study reported that most of the later patients in the series were discharged within 24 hours. Two case series reported no axillary recurrence among 100 patients followed up to 14 months, and 103 patients followed up to 18 months. For more details, refer to the Sources of evidence. # Safety Data on the safety of the procedure were not reported consistently in the studies. The incidence of seroma reported after endoscopic axillary lymph node retrieval varied from 90% (36/40) to 4% (4/100). Similarly, rates of haematoma formation ranged from 16% (16/100) in one case series to 1% (1/103) in a second case series. Other reported adverse events after endoscopic axillary lymph node retrieval included lymphocoele in 25% (5/20) of patients and wound infection in 5% (2/40) of patients. For more details, refer to the Sources of evidence. The Specialist Advisors noted that theoretical adverse effects include bleeding, damage to nerves or the axillary artery, pneumothorax, lymphoedema and pain or sensory disturbance in the arm and shoulder. # Other comments These recommendations refer to the use of endoscopy rather than open surgery for the retrieval of selected axillary lymph nodes. They do not address clinical decisions about the number of lymph nodes that should be removed. The Committee noted that this procedure is seldom carried out in the UK, and that sentinel node retrieval has become common practice. Andrew DillonChief ExecutiveDecember 2005# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedures overview of endoscopic axillary node retrieval for breast cancer', March 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication The guidance was considered for reassessment in December 2008 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It has been incorporated into the NICE pathway on early and locally advanced breast cancer, along with other related guidance and products. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of endoscopic axillary lymph node retrieval for breast cancer does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake endoscopic axillary lymph node retrieval should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. In addition, use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having endoscopic axillary lymph node retrieval for breast cancer.\n\nThis procedure should only be undertaken by surgeons skilled in endoscopic techniques.", 'The procedure': '# Indications\n\nAxillary clearance has been used as part of surgery for breast cancer. Biopsy of lymph node tissue helps in the staging of breast cancer, providing prognostic information and identifying patients who will benefit from systemic therapy.\n\nTraditionally, surgeons remove lymph nodes for staging through an incision in the axillary skin under direct vision. However, this procedure may have side effects, including wound infection and lymphoedema. There are two surgical alternatives that are standard practice. The first involves clearance to level one, two or three of the axilla, taking up to 20 lymph nodes, which provides very accurate diagnostic information. The second requires sampling of a minimum of four lymph nodes, which causes less morbidity but provides only qualitative rather than quantitative information about the status of the axillary basin of lymph nodes. A new procedure is sentinel node mapping, which requires specific training in the use of imaging. Endoscopic techniques, sometimes combined with liposuction, have been developed as a less invasive approach to removing lymph nodes for diagnosis.\n\n# Outline of the procedure\n\nIn endoscopic axillary lymph node retrieval, very small incisions are made in the axillary skin and nodes are removed using an endoscope and special instruments. The patient is placed in a supine position under general anaesthesia. Liposuction is used to remove excess axillary fat. An endoscope is inserted through the incision used for liposuction, and trocars are introduced through two additional small incisions. Fibrous tracts and small lymph and blood vessels are coagulated and cut, and lymph nodes are freed and removed. Following a saline rinse of the surgical field, the incisions are sutured. Drains are not normally required.\n\n# Efficacy\n\nConversion to open surgery was reported in 8% (4/53) of operations in a historically controlled study. In a large case series, only 2% (2/100) of operations were converted to open surgery.\n\nIn one randomised controlled trial, the operative time for endoscopic axillary lymph node retrieval was found to be significantly longer than for open surgery (mean time 61 and 33 minutes, respectively).\n\nOne quasi-randomised study found good shoulder–arm mobility at 7 days postoperatively, with more than 90% mobility being achieved after either endoscopic axillary lymph node retrieval or open surgery. Only 18% (7/40) of patients who had endoscopic axillary lymph node retrieval reported pain on the first postoperative day, compared with 33% (13/40) of patients who had open surgery. One small randomised controlled trial found that all ten patients reported no pain at 3 days after endoscopic axillary lymph node retrieval.\n\nLength of hospital stay after endoscopic axillary lymph node retrieval varied from 2.5 days to 9 days, although one study reported that most of the later patients in the series were discharged within 24 hours.\n\nTwo case series reported no axillary recurrence among 100 patients followed up to 14 months, and 103 patients followed up to 18 months. For more details, refer to the Sources of evidence.\n\n# Safety\n\nData on the safety of the procedure were not reported consistently in the studies. The incidence of seroma reported after endoscopic axillary lymph node retrieval varied from 90% (36/40) to 4% (4/100). Similarly, rates of haematoma formation ranged from 16% (16/100) in one case series to 1% (1/103) in a second case series.\n\nOther reported adverse events after endoscopic axillary lymph node retrieval included lymphocoele in 25% (5/20) of patients and wound infection in 5% (2/40) of patients. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that theoretical adverse effects include bleeding, damage to nerves or the axillary artery, pneumothorax, lymphoedema and pain or sensory disturbance in the arm and shoulder.\n\n# Other comments\n\nThese recommendations refer to the use of endoscopy rather than open surgery for the retrieval of selected axillary lymph nodes. They do not address clinical decisions about the number of lymph nodes that should be removed.\n\nThe Committee noted that this procedure is seldom carried out in the UK, and that sentinel node retrieval has become common practice.\n\nAndrew DillonChief ExecutiveDecember 2005', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedures overview of endoscopic axillary node retrieval for breast cancer', March 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': 'The guidance was considered for reassessment in December 2008 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt has been incorporated into the NICE pathway on early and locally advanced breast cancer, along with other related guidance and products.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg147
71ce5bf0cdabb8bf5d89b18c96bc2363ce31d561	nice	Retrobulbar irradiation for thyroid eye disease	Retrobulbar irradiation for thyroid eye disease # Guidance Current evidence on the safety and efficacy of retrobulbar irradiation for thyroid eye disease appears adequate to support the use of this procedure in patients for whom other treatments are inadequate or associated with significant side effects. Normal arrangements should be in place for consent, audit and clinical governance. Patient selection should be made with the involvement of a multidisciplinary team that includes an ophthalmologist, a clinical oncologist and an endocrinologist.# The procedure # Indications Thyroid eye disease (also known as dysthyroid eye disease, Graves' eye disease, Graves' ophthalmopathy and thyroid orbitopathy) affects the extraocular muscles and other orbital tissues. It is the most common cause of unilateral or bilateral proptosis in adults, due to enlarged eye muscles and an increase in the fatty tissue behind the eyes. Other symptoms include diplopia, soreness and grittiness of the eyes, with increased watering and photophobia. Most patients have mild symptoms that are controlled by conservative means. In patients with more severe disease, the eyelids may not close properly and this can result in corneal exposure and ulceration. In addition, the increased orbital tissue may cause optic nerve compression with resultant damage to sight. Steroid medication is the most commonly used treatment for thyroid eye disease. This decreases inflammation in the eye muscles and orbital tissue. Often, high-dose systemic corticosteroids are required, but these have significant side effects. If active eye disease recurs after treatment, other therapeutic options may need to be considered. Surgical orbital decompression aims to relieve severe pressure on the optic nerve. Various surgical procedures may be used to make room in the eye socket for the swollen and thickened orbital tissue. This allows the bulging eyeball to return to its normal position. Radiation therapy targeted at the tissue behind the eyeball aims to decrease orbital inflammation. It may be used alone or in combination with steroids. # Outline of the procedure Patients are commonly treated on an outpatient basis. The patient is placed in a supine position, and the head fixed with a full head shell. Irradiation is targeted at the retrobulbar contents of the orbit, delivered in about 10 sessions over a 2-week period. # Efficacy A randomised controlled trial of irradiation versus sham therapy in 88 patients with mild, untreated thyroid eye disease found a greater response rate with irradiation, using a composite outcome measure of eye function and physical properties (p = 0.02, 52% versus 27%). In a randomised controlled trial of 60 patients, improvement in eye motility was achieved in 82% (14/17) of patients following irradiation, and in 27% (4/15) of patients following sham therapy (p = 0.004). At 24 weeks, mean eye elevation was improved by 4.9° more in the patients treated with irradiation (p = 0.01). There were no significant differences in proptosis or eyelid swelling between the study arms. When irradiation was compared with prednisolone in a randomised controlled trial, there were no significant differences in eye function between the treatment arms, as measured by proptosis, visual acuity or eyelid aperture size. Self-reported eye-evaluation scores were also similar at 24 weeks. A randomised cross-over trial of 42 patients, with either the left or the right eye treated first, found no significant differences between eyes treated with irradiation and those receiving sham treatment in the outcomes of muscle volume and proptosis at 3 months following treatment. For more details, refer to the Sources of evidence. The Specialist Advisors noted that efficacy was hard to assess because of the natural history of the condition. # Safety Two case series with long-term follow-up of 7.2 and 11 years recorded the incidence of cataracts to be 10 and 11% (22/197 and 21/204), and reported retinopathy in 1% (2/197 and 2/204) of patients. One series found tumours in 5% (10/197) of patients treated with irradiation but none of these were in the area treated. Another case series found no malignant tumours in the head or neck in 157 patients followed up for a median 11 years. Mucosal thickening or polyps in the paranasal tissue were recorded in 34% (53/157) of patients followed up by CT scans. For more details, refer to the Sources of evidence. The Specialist Advisors noted that theoretical adverse events include short-term exacerbation of thyroid eye disease, dry eye, cataract, retinopathy (particularly in diabetic patients) and carcinogenesis. Andrew DillonChief ExecutiveDecember 2005# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of retrobulbar irradiation for thyroid eye disease', April 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of retrobulbar irradiation for thyroid eye disease appears adequate to support the use of this procedure in patients for whom other treatments are inadequate or associated with significant side effects. Normal arrangements should be in place for consent, audit and clinical governance.\n\nPatient selection should be made with the involvement of a multidisciplinary team that includes an ophthalmologist, a clinical oncologist and an endocrinologist.', 'The procedure': "# Indications\n\nThyroid eye disease (also known as dysthyroid eye disease, Graves' eye disease, Graves' ophthalmopathy and thyroid orbitopathy) affects the extraocular muscles and other orbital tissues. It is the most common cause of unilateral or bilateral proptosis in adults, due to enlarged eye muscles and an increase in the fatty tissue behind the eyes.\n\nOther symptoms include diplopia, soreness and grittiness of the eyes, with increased watering and photophobia. Most patients have mild symptoms that are controlled by conservative means. In patients with more severe disease, the eyelids may not close properly and this can result in corneal exposure and ulceration. In addition, the increased orbital tissue may cause optic nerve compression with resultant damage to sight.\n\nSteroid medication is the most commonly used treatment for thyroid eye disease. This decreases inflammation in the eye muscles and orbital tissue. Often, high-dose systemic corticosteroids are required, but these have significant side effects. If active eye disease recurs after treatment, other therapeutic options may need to be considered.\n\nSurgical orbital decompression aims to relieve severe pressure on the optic nerve. Various surgical procedures may be used to make room in the eye socket for the swollen and thickened orbital tissue. This allows the bulging eyeball to return to its normal position.\n\nRadiation therapy targeted at the tissue behind the eyeball aims to decrease orbital inflammation. It may be used alone or in combination with steroids.\n\n# Outline of the procedure\n\nPatients are commonly treated on an outpatient basis. The patient is placed in a supine position, and the head fixed with a full head shell. Irradiation is targeted at the retrobulbar contents of the orbit, delivered in about 10 sessions over a 2-week period.\n\n# Efficacy\n\nA randomised controlled trial of irradiation versus sham therapy in 88 patients with mild, untreated thyroid eye disease found a greater response rate with irradiation, using a composite outcome measure of eye function and physical properties (p = 0.02, 52% versus 27%).\n\nIn a randomised controlled trial of 60 patients, improvement in eye motility was achieved in 82% (14/17) of patients following irradiation, and in 27% (4/15) of patients following sham therapy (p = 0.004). At 24 weeks, mean eye elevation was improved by 4.9° more in the patients treated with irradiation (p = 0.01). There were no significant differences in proptosis or eyelid swelling between the study arms.\n\nWhen irradiation was compared with prednisolone in a randomised controlled trial, there were no significant differences in eye function between the treatment arms, as measured by proptosis, visual acuity or eyelid aperture size. Self-reported eye-evaluation scores were also similar at 24 weeks.\n\nA randomised cross-over trial of 42 patients, with either the left or the right eye treated first, found no significant differences between eyes treated with irradiation and those receiving sham treatment in the outcomes of muscle volume and proptosis at 3 months following treatment. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that efficacy was hard to assess because of the natural history of the condition.\n\n# Safety\n\nTwo case series with long-term follow-up of 7.2 and 11 years recorded the incidence of cataracts to be 10 and 11% (22/197 and 21/204), and reported retinopathy in 1% (2/197 and 2/204) of patients. One series found tumours in 5% (10/197) of patients treated with irradiation but none of these were in the area treated. Another case series found no malignant tumours in the head or neck in 157 patients followed up for a median 11 years. Mucosal thickening or polyps in the paranasal tissue were recorded in 34% (53/157) of patients followed up by CT scans. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that theoretical adverse events include short-term exacerbation of thyroid eye disease, dry eye, cataract, retinopathy (particularly in diabetic patients) and carcinogenesis.\n\nAndrew DillonChief ExecutiveDecember 2005", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of retrobulbar irradiation for thyroid eye disease', April 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg148
5c79dab37339ad665bb59290b2551b32f36d19cd	nice	Division of ankyloglossia (tongue-tie) for breastfeeding	Division of ankyloglossia (tongue-tie) for breastfeeding # Guidance Current evidence suggests that there are no major safety concerns about division of ankyloglossia (tongue-tie) and limited evidence suggests that this procedure can improve breastfeeding. This evidence is adequate to support the use of the procedure provided that normal arrangements are in place for consent, audit and clinical governance. Division of ankyloglossia (tongue-tie) for breastfeeding should only be performed by registered healthcare professionals who are properly trained. Publication of further controlled trials on the effect of the procedure on successful long-term breastfeeding will be useful.# The procedure # Indications Ankyloglossia, also known as tongue-tie, is a congenital anomaly characterised by an abnormally short lingual frenulum, which may restrict mobility of the tongue. It varies from a mild form in which the tongue is bound only by a thin mucous membrane, to a severe form in which the tongue is completely fused to the floor of the mouth. Breastfeeding difficulties may arise, such as problems with latching (getting the mother and baby appropriately positioned to breastfeed successfully), sore nipples and poor infant weight gain. Many tongue-ties are asymptomatic and cause no problems. Some babies with tongue-tie have breastfeeding difficulties. Conservative management includes breastfeeding advice, and careful assessment is important to determine whether the frenulum is interfering with feeding and whether its division is appropriate. Some practitioners believe that if division is required, this should be undertaken as early as possible. This may enable the mother to continue to breastfeed, rather than having to feed artificially. # Outline of the procedure In early infancy, division of the tongue-tie is usually performed without anaesthesia, although local anaesthetic is sometimes used. The baby's head is stabilised, and sharp, blunt-ended scissors are used to divide the lingual frenulum. There should be little or no blood loss and feeding may be resumed immediately. After the early months of life, general anaesthesia is usually required. # Efficacy One randomised controlled trial compared division of tongue-tie with 48 hours of intensive support from a lactation consultant. Mothers reported that 95% (19/20) of babies had improved breastfeeding 48 hours after tongue-tie division, compared with 5% (1/20) of babies in the control group (p < 0.001). In one case series of 215 babies, 80% (173/215) of mothers reported improved breastfeeding 24 hours after the procedure. In another case series of 123 babies, 100% (70/70) of mothers reported improved latch after the procedure, and the 53 mothers with nipple pain noted significant improvement immediately after the procedure. In a third case series, 100% (36/36) of babies were reported to have normal tongue motion at 3 months. For more details, refer to the Sources of evidence. There were conflicting opinions among the Specialist Advisors and some stated that it is difficult to be certain whether any perceived improvement in breastfeeding is due to division of the tongue-tie. # Safety Few adverse effects were reported. One case series reported that, after the procedure, 2% (4/215) of babies had an ulcer under the tongue for more than 48 hours. Two studies, including a total of 159 babies, stated that there were no complications. Two studies reported that 8% (3/36) and 18% (39/215) of babies slept through the procedure. For more details, refer to the Sources of evidence. The Specialist Advisors stated that adverse effects were likely to be rare. Potential adverse events include bleeding, infection, ulceration, pain, damage to the tongue and submandibular ducts, and recurrence of the tongue-tie. # Other comments It was recognised that breastfeeding is a complex interaction between mother and child, and that many factors can affect the ability to feed. Skilled breastfeeding support is an integral part of the management of breastfeeding difficulties. Public consultation highlighted that this procedure may also be relevant for bottle feeding, but it was noted that this was not included in the scope or in the literature search for this guidance.# Further information The Institute has developed a clinical guideline on postnatal care. The Health Development Agency has also published a systematic review on breastfeeding. Andrew DillonChief ExecutiveDecember 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of division of ankyloglossia (tongue-tie) for breastfeeding', February 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It has been incorporated into the NICE pathway on postnatal care, along with other related guidance and products. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence suggests that there are no major safety concerns about division of ankyloglossia (tongue-tie) and limited evidence suggests that this procedure can improve breastfeeding. This evidence is adequate to support the use of the procedure provided that normal arrangements are in place for consent, audit and clinical governance.\n\nDivision of ankyloglossia (tongue-tie) for breastfeeding should only be performed by registered healthcare professionals who are properly trained.\n\nPublication of further controlled trials on the effect of the procedure on successful long-term breastfeeding will be useful.', 'The procedure': "# Indications\n\nAnkyloglossia, also known as tongue-tie, is a congenital anomaly characterised by an abnormally short lingual frenulum, which may restrict mobility of the tongue. It varies from a mild form in which the tongue is bound only by a thin mucous membrane, to a severe form in which the tongue is completely fused to the floor of the mouth. Breastfeeding difficulties may arise, such as problems with latching (getting the mother and baby appropriately positioned to breastfeed successfully), sore nipples and poor infant weight gain.\n\nMany tongue-ties are asymptomatic and cause no problems. Some babies with tongue-tie have breastfeeding difficulties. Conservative management includes breastfeeding advice, and careful assessment is important to determine whether the frenulum is interfering with feeding and whether its division is appropriate. Some practitioners believe that if division is required, this should be undertaken as early as possible. This may enable the mother to continue to breastfeed, rather than having to feed artificially.\n\n# Outline of the procedure\n\nIn early infancy, division of the tongue-tie is usually performed without anaesthesia, although local anaesthetic is sometimes used. The baby's head is stabilised, and sharp, blunt-ended scissors are used to divide the lingual frenulum. There should be little or no blood loss and feeding may be resumed immediately. After the early months of life, general anaesthesia is usually required.\n\n# Efficacy\n\nOne randomised controlled trial compared division of tongue-tie with 48 hours of intensive support from a lactation consultant. Mothers reported that 95% (19/20) of babies had improved breastfeeding 48 hours after tongue-tie division, compared with 5% (1/20) of babies in the control group (p < 0.001).\n\nIn one case series of 215 babies, 80% (173/215) of mothers reported improved breastfeeding 24 hours after the procedure. In another case series of 123 babies, 100% (70/70) of mothers reported improved latch after the procedure, and the 53 mothers with nipple pain noted significant improvement immediately after the procedure. In a third case series, 100% (36/36) of babies were reported to have normal tongue motion at 3 months. For more details, refer to the Sources of evidence.\n\nThere were conflicting opinions among the Specialist Advisors and some stated that it is difficult to be certain whether any perceived improvement in breastfeeding is due to division of the tongue-tie.\n\n# Safety\n\nFew adverse effects were reported. One case series reported that, after the procedure, 2% (4/215) of babies had an ulcer under the tongue for more than 48 hours. Two studies, including a total of 159 babies, stated that there were no complications.\n\nTwo studies reported that 8% (3/36) and 18% (39/215) of babies slept through the procedure. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that adverse effects were likely to be rare. Potential adverse events include bleeding, infection, ulceration, pain, damage to the tongue and submandibular ducts, and recurrence of the tongue-tie.\n\n# Other comments\n\nIt was recognised that breastfeeding is a complex interaction between mother and child, and that many factors can affect the ability to feed. Skilled breastfeeding support is an integral part of the management of breastfeeding difficulties.\n\nPublic consultation highlighted that this procedure may also be relevant for bottle feeding, but it was noted that this was not included in the scope or in the literature search for this guidance.", 'Further information': "The Institute has developed a clinical guideline on postnatal care. The Health Development Agency has also published a systematic review on breastfeeding.\n\nAndrew DillonChief ExecutiveDecember 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of division of ankyloglossia (tongue-tie) for breastfeeding', February 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt has been incorporated into the NICE pathway on postnatal care, along with other related guidance and products.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg149
c1c1c3c46bf1c0d36a158caa435bf3a960a89d74	nice	Electrosurgery (diathermy and coblation) for tonsillectomy	Electrosurgery (diathermy and coblation) for tonsillectomy # Guidance This document replaces previous guidance on coblation tonsillectomy (NICE interventional procedures guidance 9) and interim guidance on diathermy for tonsillectomy that was issued jointly with the British Association of Otorhinolaryngologists – Head and Neck Surgeons. Current evidence on the safety and efficacy of electrosurgery (diathermy and coblation) for tonsillectomy appears adequate to support the use of these techniques, provided that normal arrangements are in place for consent, audit and clinical governance. Surgeons should avoid excessive use of diathermy during tonsillectomy. Surgeons using diathermy in tonsillectomy for dissection and/or haemostasis should be fully trained in its use and should understand the potential complications. Use of coblation for tonsillectomy can result in higher rates of haemorrhage than other techniques and clinicians wishing to use coblation should be specifically trained. The British Association of Otorhinolaryngologists – Head and Neck Surgeons has agreed to produce standards for training. Surgeons should ensure that patients or their parents/carers understand the risk of haemorrhage after tonsillectomy using these techniques. In addition, use of the Institute's information for the public is recommended. Surgeons should audit and review the rates of haemorrhage complicating tonsillectomy in their own practices and in the context of the techniques they use. Publication of further information about the influence of different techniques and other factors (such as age) on the incidence of haemorrhage after tonsillectomy would be useful in guiding future practice.# The procedure # Indications Indications for tonsillectomy include recurrent acute or chronic tonsillitis, peritonsillar abscess and pharyngeal obstruction/obstructive sleep apnoea. Life-threatening complications of these conditions are rare and the main aim of surgery is to relieve symptoms. Traditional 'cold steel' tonsillectomy consists of two stages: removal of the tonsil followed by haemostasis. Bleeding is controlled by pressure, followed by ligatures. Ligatures may be supplemented by diathermy and the use of packs. # Outline of the procedure Diathermy uses radiofrequency energy applied directly to the tissue, and can be bipolar (current passes between the two tips of the forceps) or monopolar (current passes between the forceps tips and a plate attached to the patient's skin). The heat generated may be used in dissection to incise the mucosa and divide the strands of tissue that bind the tonsil to the pharyngeal wall. It may also be used for haemostasis, by coagulating the vessels that run in these strands and any other bleeding vessels. Coblation involves passing a radiofrequency bipolar electrical current through a medium of normal saline, producing a plasma field of sodium ions that dissects the tissue by disrupting intercellular bonds leading to tissue vaporisation. Coblation heats surrounding tissue less than diathermy. # Efficacy A systematic review of the published evidence on electrosurgery (diathermy and coblation) for tonsillectomy was commissioned by the Institute and completed in June 2005. The mean operating time across the 18 studies that reported this outcome was shortest for diathermy (mean 16.6 minutes), followed by cold steel with ligatures and/or diathermy haemostasis (mean 18.2 minutes). The longest time taken was with coblation (mean 24.5 minutes). No test of statistical significance between lengths of operating times was undertaken in analysis. Four studies looked at the time taken to return to a normal diet after tonsillectomy using diathermy versus cold steel for dissection. Three of the studies favoured cold steel (range 5–9 days for cold steel compared with 7–11 days for diathermy) while the fourth study favoured diathermy. Of two studies investigating the time taken to return to a normal diet after tonsillectomy using diathermy versus coblation, one study favoured diathermy (mean 6.7 days after diathermy compared with 7.4 days after coblation, p = 0.4) and the other favoured coblation (mean 2.4 days after coblation versus 7.6 days after diathermy, p < 0.0001). For more details refer to Sources of evidence. # Safety Bleeding is an important complication of tonsillectomy. It can occur intraoperatively, during the first 24 hours after the operation (defined in most studies as primary haemorrhage), or after 24 hours (secondary haemorrhage). Postoperative haemorrhage may require the patient to be readmitted to hospital and possibly undergo further surgery. ## Primary haemorrhage Data from the systematic review and from the Wales Single-use Instrument Surveillance Programme (SISP; 3690 patients) indicated that the highest rates of primary haemorrhage requiring return to theatre were associated with cold steel dissection with ligature haemostasis (1.1% and 0.9%, respectively). By contrast, data from the National Prospective Tonsillectomy Audit (which covered England and Northern Ireland; 33,921 patients) indicated that the lowest rates of primary haemorrhage requiring return to theatre were associated with cold steel dissection with bipolar diathermy haemostasis; and with bipolar diathermy dissection and haemostasis (both 0.3%, 95% confidence interval 0.2–0.4%). The highest rates were associated with monopolar diathermy dissection and haemostasis (0.9%, 95% CI 0.3–2.3%), and with coblation (1.1%, 95% CI 0.7–1.7%). Data from the National Prospective Tonsillectomy Audit final report on rates for all primary haemorrhage indicated that the lowest rates were associated with bipolar diathermy dissection and haemostasis, and with cold steel dissection combined with diathermy haemostasis. The highest rates were associated with coblation, and with monopolar diathermy dissection and haemostasis. ## Secondary haemorrhage Crude overall data from the studies included in the systematic review and data from the Wales SISP suggested that cold steel dissection with ligature haemostasis was associated with lower rates of secondary haemorrhage requiring return to theatre, while use of diathermy for dissection and haemostasis was associated with higher rates. In the National Prospective Tonsillectomy Audit final report, the lowest rate of secondary haemorrhage requiring return to theatre was associated with cold steel dissection with ligature haemostasis (0.2%, 95% CI 0.1–0.4%). Higher rates were associated with cold steel dissection with diathermy haemostasis (0.3%, 95% CI 0.1–0.7% with monopolar diathermy; and 0.4%, 95% CI 0.3–0.5% with bipolar). The highest rates of secondary haemorrhage requiring return to theatre were associated with coblation (0.7%, 95% CI 0.4–1.3%), and with diathermy dissection and haemostasis (0.7%, 95% CI 0.2–1.9% with monopolar diathermy; and 0.8%, 95% CI 0.6–0.9% with bipolar). A similar pattern was observed for all secondary haemorrhages (both those requiring and those not requiring further operation). The lowest rates were associated with cold steel dissection with ligature haemostasis, higher rates with cold steel dissection and diathermy haemostasis, and the highest rates with coblation and with diathermy for both dissection and haemostasis. For more details, refer to the Sources of evidence. # Other comments It was noted that the recommendations of the National Prospective Tonsillectomy Audit were that all surgeons undertaking tonsillectomy should be trained in the use of cold steel dissection and ligature haemostasis, as well as the use of any electrosurgical techniques. It was noted that it would be helpful for all diathermy equipment to record the total amount of energy used during each operation. The Medicines and Healthcare products Regulatory Agency is addressing this issue.# Further information The National Prospective Tonsillectomy Audit was published in May 2005, and contains recommendations for tonsillectomy. Andrew DillonChief ExecutiveDecember 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Systematic review of the safety and efficacy of electrosurgery for tonsillectomy', May 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It updates and replaces NICE interventional procedure guidance 9. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "This document replaces previous guidance on coblation tonsillectomy (NICE interventional procedures guidance 9) and interim guidance on diathermy for tonsillectomy that was issued jointly with the British Association of Otorhinolaryngologists – Head and Neck Surgeons.\n\nCurrent evidence on the safety and efficacy of electrosurgery (diathermy and coblation) for tonsillectomy appears adequate to support the use of these techniques, provided that normal arrangements are in place for consent, audit and clinical governance.\n\nSurgeons should avoid excessive use of diathermy during tonsillectomy. Surgeons using diathermy in tonsillectomy for dissection and/or haemostasis should be fully trained in its use and should understand the potential complications.\n\nUse of coblation for tonsillectomy can result in higher rates of haemorrhage than other techniques and clinicians wishing to use coblation should be specifically trained. The British Association of Otorhinolaryngologists – Head and Neck Surgeons has agreed to produce standards for training.\n\nSurgeons should ensure that patients or their parents/carers understand the risk of haemorrhage after tonsillectomy using these techniques. In addition, use of the Institute's information for the public is recommended.\n\nSurgeons should audit and review the rates of haemorrhage complicating tonsillectomy in their own practices and in the context of the techniques they use. Publication of further information about the influence of different techniques and other factors (such as age) on the incidence of haemorrhage after tonsillectomy would be useful in guiding future practice.", 'The procedure': "# Indications\n\nIndications for tonsillectomy include recurrent acute or chronic tonsillitis, peritonsillar abscess and pharyngeal obstruction/obstructive sleep apnoea. Life-threatening complications of these conditions are rare and the main aim of surgery is to relieve symptoms.\n\nTraditional 'cold steel' tonsillectomy consists of two stages: removal of the tonsil followed by haemostasis. Bleeding is controlled by pressure, followed by ligatures. Ligatures may be supplemented by diathermy and the use of packs.\n\n# Outline of the procedure\n\nDiathermy uses radiofrequency energy applied directly to the tissue, and can be bipolar (current passes between the two tips of the forceps) or monopolar (current passes between the forceps tips and a plate attached to the patient's skin). The heat generated may be used in dissection to incise the mucosa and divide the strands of tissue that bind the tonsil to the pharyngeal wall. It may also be used for haemostasis, by coagulating the vessels that run in these strands and any other bleeding vessels.\n\nCoblation involves passing a radiofrequency bipolar electrical current through a medium of normal saline, producing a plasma field of sodium ions that dissects the tissue by disrupting intercellular bonds leading to tissue vaporisation. Coblation heats surrounding tissue less than diathermy.\n\n# Efficacy\n\nA systematic review of the published evidence on electrosurgery (diathermy and coblation) for tonsillectomy was commissioned by the Institute and completed in June 2005.\n\nThe mean operating time across the 18 studies that reported this outcome was shortest for diathermy (mean 16.6 minutes), followed by cold steel with ligatures and/or diathermy haemostasis (mean 18.2 minutes). The longest time taken was with coblation (mean 24.5 minutes). No test of statistical significance between lengths of operating times was undertaken in analysis.\n\nFour studies looked at the time taken to return to a normal diet after tonsillectomy using diathermy versus cold steel for dissection. Three of the studies favoured cold steel (range 5–9 days for cold steel compared with 7–11 days for diathermy) while the fourth study favoured diathermy. Of two studies investigating the time taken to return to a normal diet after tonsillectomy using diathermy versus coblation, one study favoured diathermy (mean 6.7 days after diathermy compared with 7.4 days after coblation, p = 0.4) and the other favoured coblation (mean 2.4 days after coblation versus 7.6 days after diathermy, p < 0.0001). For more details refer to Sources of evidence.\n\n# Safety\n\nBleeding is an important complication of tonsillectomy. It can occur intraoperatively, during the first 24 hours after the operation (defined in most studies as primary haemorrhage), or after 24 hours (secondary haemorrhage). Postoperative haemorrhage may require the patient to be readmitted to hospital and possibly undergo further surgery.\n\n## Primary haemorrhage\n\nData from the systematic review and from the Wales Single-use Instrument Surveillance Programme (SISP; 3690 patients) indicated that the highest rates of primary haemorrhage requiring return to theatre were associated with cold steel dissection with ligature haemostasis (1.1% and 0.9%, respectively). By contrast, data from the National Prospective Tonsillectomy Audit (which covered England and Northern Ireland; 33,921 patients) indicated that the lowest rates of primary haemorrhage requiring return to theatre were associated with cold steel dissection with bipolar diathermy haemostasis; and with bipolar diathermy dissection and haemostasis (both 0.3%, 95% confidence interval [CI] 0.2–0.4%). The highest rates were associated with monopolar diathermy dissection and haemostasis (0.9%, 95% CI 0.3–2.3%), and with coblation (1.1%, 95% CI 0.7–1.7%).\n\nData from the National Prospective Tonsillectomy Audit final report on rates for all primary haemorrhage indicated that the lowest rates were associated with bipolar diathermy dissection and haemostasis, and with cold steel dissection combined with diathermy haemostasis. The highest rates were associated with coblation, and with monopolar diathermy dissection and haemostasis.\n\n## Secondary haemorrhage\n\nCrude overall data from the studies included in the systematic review and data from the Wales SISP suggested that cold steel dissection with ligature haemostasis was associated with lower rates of secondary haemorrhage requiring return to theatre, while use of diathermy for dissection and haemostasis was associated with higher rates. In the National Prospective Tonsillectomy Audit final report, the lowest rate of secondary haemorrhage requiring return to theatre was associated with cold steel dissection with ligature haemostasis (0.2%, 95% CI 0.1–0.4%). Higher rates were associated with cold steel dissection with diathermy haemostasis (0.3%, 95% CI 0.1–0.7% with monopolar diathermy; and 0.4%, 95% CI 0.3–0.5% with bipolar). The highest rates of secondary haemorrhage requiring return to theatre were associated with coblation (0.7%, 95% CI 0.4–1.3%), and with diathermy dissection and haemostasis (0.7%, 95% CI 0.2–1.9% with monopolar diathermy; and 0.8%, 95% CI 0.6–0.9% with bipolar).\n\nA similar pattern was observed for all secondary haemorrhages (both those requiring and those not requiring further operation). The lowest rates were associated with cold steel dissection with ligature haemostasis, higher rates with cold steel dissection and diathermy haemostasis, and the highest rates with coblation and with diathermy for both dissection and haemostasis. For more details, refer to the Sources of evidence.\n\n# Other comments\n\nIt was noted that the recommendations of the National Prospective Tonsillectomy Audit were that all surgeons undertaking tonsillectomy should be trained in the use of cold steel dissection and ligature haemostasis, as well as the use of any electrosurgical techniques.\n\nIt was noted that it would be helpful for all diathermy equipment to record the total amount of energy used during each operation. The Medicines and Healthcare products Regulatory Agency is addressing this issue.", 'Further information': "The National Prospective Tonsillectomy Audit was published in May 2005, and contains recommendations for tonsillectomy.\n\nAndrew DillonChief ExecutiveDecember 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Systematic review of the safety and efficacy of electrosurgery for tonsillectomy', May 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt updates and replaces NICE interventional procedure guidance 9.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg150
a3223d51fe5e9799ebd92a6183abeb74a30d0a6f	nice	Direct C1 lateral mass screw for cervical spine stabilisation	Direct C1 lateral mass screw for cervical spine stabilisation # Guidance Current evidence on the safety and efficacy of direct C1 lateral mass screw for cervical spine stabilisation appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. This procedure should be performed only in specialist units where surgery of the cervical spine is routinely undertaken.# The procedure # Indications Atlantoaxial instability (excessive movement between the first and second cervical vertebrae) can be caused by trauma, malignancy and inflammatory or congenital defects. It can present with local pain, but if the spinal cord is compressed it can cause clumsiness, lack of coordination, difficulty walking and, rarely, paralysis or death. Treatment is by stabilisation of the C1 (atlas) on to the C2 (axial) vertebra. Traditional methods of atlantoaxial fusion involve using wires and bone grafts, but these require external support in the postoperative period, including halo devices. Methods of rigid fixation with transarticular screws between C1 and C2 have been described. These do not require external fixation, but are not appropriate for every patient. # Outline of the procedure Under general anaesthesia, the patient is placed in the prone position and standard posterior exposure of the cervical spine is performed. Screws are inserted into the lateral masses of C1 and fixed by rods corresponding to screws in the lateral masses or pedicles of C2. The posterior arch of bone compressing the spinal cord may be removed. An onlay graft of bone permits a permanent fusion between C1 and C2. # Efficacy The primary endpoint in the literature was successful fusion. In two case series of 37 and 160 patients and one case report, immobilisation of C1 on C2 was achieved in 196 patients (in the remaining two patients the intent was not to procure fusion, see Sources of evidence for more information). In a case series of 157 patients, clinical and neurological recovery was documented in 100% but assessment measures were not described. A case series investigating a lateral mass and plate system reported that 6% (9/157) of procedures could not be completed because of inadequate exposure of the atlantoaxial region. For more details refer to the Sources of evidence. The Specialist Advisors considered this to be a variation on existing fusion techniques. # Safety In two case series of 157 and 37 patients, there were no reports of implant failure. No vertebral artery injuries occurred in the three case series (n = 212) or in the one case report where safety outcomes were reported. In a case series, sensory loss in the distribution of the C2 nerve root was reported by 11% (18/157) of patients undergoing screw and plate fixation. In the same series, six screws were found to be penetrating more than 4 mm from the anterior cortex of C1 but with no clinical complications. One screw was found to be broken at 18 months' follow-up. In another case series, deep wound infection was reported in 3% (1/37) of patients. For more details refer to the Sources of evidence. The Specialist Advisors stated that potential adverse events include haemorrhage from the vertebral venous plexus and screw failure or loosening. Less common but more serious complications may include injury to the vertebral artery, and spinal cord injury caused by screw misplacement. # Other comments It was recognised that the evidence on this procedure was limited, but it was considered sufficient in the context of the conditions requiring treatment. These recommendations are based on evidence from studies using two different techniques – the plate system and the more recent polyaxial screw and rod systems. Andrew DillonChief ExecutiveDecember 2005# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of direct C1 lateral screw procedure for cervical spine stabilisation', February 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of direct C1 lateral mass screw for cervical spine stabilisation appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThis procedure should be performed only in specialist units where surgery of the cervical spine is routinely undertaken.', 'The procedure': "# Indications\n\nAtlantoaxial instability (excessive movement between the first and second cervical vertebrae) can be caused by trauma, malignancy and inflammatory or congenital defects. It can present with local pain, but if the spinal cord is compressed it can cause clumsiness, lack of coordination, difficulty walking and, rarely, paralysis or death. Treatment is by stabilisation of the C1 (atlas) on to the C2 (axial) vertebra.\n\nTraditional methods of atlantoaxial fusion involve using wires and bone grafts, but these require external support in the postoperative period, including halo devices. Methods of rigid fixation with transarticular screws between C1 and C2 have been described. These do not require external fixation, but are not appropriate for every patient.\n\n# Outline of the procedure\n\nUnder general anaesthesia, the patient is placed in the prone position and standard posterior exposure of the cervical spine is performed. Screws are inserted into the lateral masses of C1 and fixed by rods corresponding to screws in the lateral masses or pedicles of C2. The posterior arch of bone compressing the spinal cord may be removed. An onlay graft of bone permits a permanent fusion between C1 and C2.\n\n# Efficacy\n\nThe primary endpoint in the literature was successful fusion. In two case series of 37 and 160 patients and one case report, immobilisation of C1 on C2 was achieved in 196 patients (in the remaining two patients the intent was not to procure fusion, see Sources of evidence for more information).\n\nIn a case series of 157 patients, clinical and neurological recovery was documented in 100% but assessment measures were not described.\n\nA case series investigating a lateral mass and plate system reported that 6% (9/157) of procedures could not be completed because of inadequate exposure of the atlantoaxial region. For more details refer to the Sources of evidence.\n\nThe Specialist Advisors considered this to be a variation on existing fusion techniques.\n\n# Safety\n\nIn two case series of 157 and 37 patients, there were no reports of implant failure. No vertebral artery injuries occurred in the three case series (n = 212) or in the one case report where safety outcomes were reported.\n\nIn a case series, sensory loss in the distribution of the C2 nerve root was reported by 11% (18/157) of patients undergoing screw and plate fixation. In the same series, six screws were found to be penetrating more than 4 mm from the anterior cortex of C1 but with no clinical complications. One screw was found to be broken at 18 months' follow-up. In another case series, deep wound infection was reported in 3% (1/37) of patients. For more details refer to the Sources of evidence.\n\nThe Specialist Advisors stated that potential adverse events include haemorrhage from the vertebral venous plexus and screw failure or loosening. Less common but more serious complications may include injury to the vertebral artery, and spinal cord injury caused by screw misplacement.\n\n# Other comments\n\nIt was recognised that the evidence on this procedure was limited, but it was considered sufficient in the context of the conditions requiring treatment.\n\nThese recommendations are based on evidence from studies using two different techniques – the plate system and the more recent polyaxial screw and rod systems.\n\nAndrew DillonChief ExecutiveDecember 2005", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of direct C1 lateral screw procedure for cervical spine stabilisation', February 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg146
05e8179ba3835b9296bb4bde8691862764499175	nice	Obsessive-compulsive disorder and body dysmorphic disorder: treatment	Obsessive-compulsive disorder and body dysmorphic disorder: treatment This guideline covers recognising, assessing, diagnosing and treating obsessive-compulsive disorder and body dysmorphic disorder in adults, young people and children (aged 8 years and older). It aims to improve the diagnosis and treatment of obsessive-compulsive disorder and body dysmorphic disorder. It includes recommendations on how families and carers may be able to support people with either of these conditions, and how they can get support for themselves. # Introduction Obsessive‑compulsive disorder (OCD) is characterised by the presence of either obsessions or compulsions, but commonly both. The symptoms can cause significant functional impairment and/or distress. An obsession is defined as an unwanted intrusive thought, image or urge that repeatedly enters the person's mind. Compulsions are repetitive behaviours or mental acts that the person feels driven to perform. A compulsion can either be overt and observable by others, such as checking that a door is locked, or a covert mental act that cannot be observed, such as repeating a certain phrase in one's mind. It is thought that 1% to 2% of the population have OCD, although some studies have estimated 2% to 3%. Body dysmorphic disorder (BDD) is characterised by a preoccupation with an imagined defect in one's appearance, or in the case of a slight physical anomaly, the person's concern is markedly excessive. BDD is characterised by time‑consuming behaviours such as mirror gazing, comparing particular features to those of others, excessive camouflaging tactics to hide the defect, skin picking and reassurance seeking. It is thought that 0.5% to 0.7% of the population have BDD. The recommendations in this guideline were graded according to the quality of the evidence they were based on. The gradings are available in the full guideline and are not shown in this web version.# Recommendations People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care. Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding. # Principles of care for all people with OCD or BDD and their families or carers ## Understanding People with obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) are often ashamed and embarrassed by their condition and may find it very difficult to discuss their symptoms with healthcare professionals, friends, family or carers. Healthcare professionals should help patients, and their families or carers where appropriate, to understand the involuntary nature of the symptoms by providing accurate information in an appropriate format on current understanding of the disorders from psychological and/or biological perspectives. When assessing people with OCD or BDD, healthcare professionals should sensitively explore the hidden distress and disability commonly associated with the disorders, providing explanation and information wherever necessary. In particular, people with OCD who are distressed by their obsessive thoughts should be informed that such thoughts are occasionally experienced by almost everybody, and when frequent and distressing are a typical feature of OCD. ## Continuity of care OCD and BDD are frequently recurring or chronic conditions that often affect some of the most intimate aspects of a person's life. Healthcare professionals should therefore ensure continuity of care and minimise the need for multiple assessments by different healthcare professionals. Because OCD and BDD may occur across a person's lifespan, particular care should be given to the provision of appropriate care at all ages and a seamless transition between services aimed at specific ages, such as the transition from services for young people to services for adults. Careful consideration should be given to the effective integration and coordination of care of people with OCD and BDD across both primary and secondary care. There should be clear, written agreement among individual healthcare professionals about the responsibility for monitoring and treating people with OCD and BDD. A written copy of this agreement should be given to the patient. This should be in collaboration with the patient, and where appropriate: the Care Programme Approach (CPA) should be used the patient's family or carers should be involved healthcare professionals should liaise with other professionals involved in providing care and support to the patient. ## Information and support Treatment and care should take into account the individual needs and preferences of people with OCD or BDD. Patients should have the opportunity to make informed decisions about their care and treatment. Where patients do not have the capacity to make decisions, or children or young people are not old enough to do so, healthcare professionals should follow the Department of Health's Reference guide to consent for examination or treatment. Good communication between healthcare professionals and people with OCD or BDD is essential. Provision of information, treatment and care should be tailored to the needs of the individual, culturally appropriate, and provided in a form that is accessible to people who have additional needs, such as learning difficulties, physical or sensory disabilities, or limited competence in speaking or reading English. Healthcare professionals should consider informing people with OCD or BDD and their family or carers about local self‑help and support groups, and encourage them to participate in such groups where appropriate. ## Religion and culture Obsessive‑compulsive symptoms may sometimes involve a person's religion, such as religious obsessions and scrupulosity, or cultural practices. When the boundary between religious or cultural practice and obsessive‑compulsive symptoms is unclear, healthcare professionals should, with the patient's consent, consider seeking the advice and support of an appropriate religious or community leader to support the therapeutic process. ## Families and carers Because OCD and BDD often have an impact on families and carers, healthcare professionals should promote a collaborative approach with people with OCD or BDD and their family or carers, wherever this is appropriate and possible. In the treatment and care of people with OCD or BDD, family members or carers should be provided with good information (both verbal and written) about the disorder, its likely causes, its course and its treatment. Assessment and treatment plans for people with OCD or BDD should, where appropriate, involve relevant family members or carers. In some cases, particularly with children and young people, when the symptoms of OCD or BDD interfere with academic or workplace performance, it may be appropriate to liaise with professionals from these organisations. Assessment should include the impact of rituals and compulsions on others (in particular on dependent children) and the degree to which carers are involved in supporting or carrying out behaviours related to the disorder. If dependent children are considered to be at risk of emotional, social or mental health problems as a result of the behaviour of a parent with OCD or BDD and/or the child's involvement in related activity, independent assessment of the child should be requested. If this is carried out, the parent should be kept informed at every stage of the assessment. In the treatment of people with OCD or BDD, especially when the disorder is moderate to severe or chronic, an assessment of their carer's social, occupational and mental health needs should be offered. See NICE's guideline on supporting adult carers. # Stepped care for adults, young people and children with OCD or BDD The stepped‑care model draws attention to the different needs of people with OCD and BDD, depending on the characteristics of their disorder, their personal and social circumstances, their age, and the responses that are required from services. It provides a framework in which to organise the provision of services in order to identify and access the most effective interventions (see figure 1). ## Figure 1 The stepped-care model The full guideline contains figure 1. Stepped care attempts to provide the most effective but least intrusive treatments appropriate to a person's needs. It assumes that the course of the disorder is monitored and referral to the appropriate level of care is made depending on the person's difficulties. Each step introduces additional interventions; the higher steps normally assume interventions in the previous step have been offered and/or attempted, but there are situations where an individual may be referred to any appropriate level. The guidance follows the steps in the figure. At all stages of assessment and treatment, families or carers should be involved as appropriate. This is particularly important in the treatment of children and young people with OCD or BDD where it may also be helpful to involve others in their network, for example teachers, school health advisors, educational psychologists, and educational social workers. # Step 1: awareness and recognition Although the more common forms of OCD are likely to be recognised when people report symptoms, less common forms of OCD and many cases of BDD may remain unrecognised, sometimes for many years. Relatively few mental health professionals or GPs have expertise in the recognition, assessment, diagnosis and treatment of the less common forms of OCD and BDD. Each primary care trust, mental healthcare trust and children's trust that provides mental health services should have access to a specialist OCD/BDD multidisciplinary team offering age‑appropriate care. This team would perform the following functions: increase the skills of mental health professionals in the assessment and evidence‑based treatment of people with OCD or BDD, provide high‑quality advice, understand family and developmental needs, and, when appropriate, conduct expert assessment and specialist cognitive‑behavioural and pharmacological treatment. Specialist mental healthcare professionals in OCD or BDD should collaborate with local and national voluntary organisations to increase awareness and understanding of the disorders and improve access to high‑quality information about them. Such information should also be made available to primary and secondary healthcare professionals, and to professionals from other public services who may come into contact with people of any age with OCD or BDD. Specialist OCD/BDD teams should collaborate with people with OCD or BDD and their families or carers to provide training for all mental health professionals, cosmetic surgeons and dermatology professionals. # Step 2: recognition and assessment ## OCD For people known to be at higher risk of OCD (such as individuals with symptoms of depression, anxiety, alcohol or substance misuse, BDD or an eating disorder), or for people attending dermatology clinics, healthcare professionals should routinely consider and explore the possibility of comorbid OCD by asking direct questions about possible symptoms such as the following. Do you wash or clean a lot? Do you check things a lot? Is there any thought that keeps bothering you that you would like to get rid of but cannot? Do your daily activities take a long time to finish? Are you concerned about putting things in a special order or are you very upset by mess? Do these problems trouble you? In people who have been diagnosed with OCD, healthcare professionals should assess the risk of self‑harm and suicide, especially if they have also been diagnosed with depression. Part of the risk assessment should include the impact of their compulsive behaviours on themselves or others. Other comorbid conditions and psychosocial factors that may contribute to risk should also be considered. If healthcare professionals are uncertain about the risks associated with intrusive sexual, aggressive or death‑related thoughts reported by people with OCD, they should consult mental health professionals with specific expertise in the assessment and management of OCD. These themes are common in people with OCD at any age, and are often misinterpreted as indicating risk. ## BDD For people known to be at higher risk of BDD (such as individuals with symptoms of depression, social phobia, alcohol or substance misuse, OCD or an eating disorder), or for people with mild disfigurements or blemishes who are seeking a cosmetic or dermatological procedure, healthcare professionals should routinely consider and explore the possibility of BDD. In the assessment of people at higher risk of BDD, the following 5 questions should be asked to help identify individuals with BDD. Do you worry a lot about the way you look and wish you could think about it less? What specific concerns do you have about your appearance? On a typical day, how many hours a day is your appearance on your mind? (More than 1 hour a day is considered excessive.) What effect does it have on your life? Does it make it hard to do your work or be with friends? People with suspected or diagnosed BDD seeking cosmetic surgery or dermatological treatment should be assessed by a mental health professional with specific expertise in the management of BDD. In people who have been diagnosed with BDD, healthcare professionals should assess the risk of self‑harm and suicide, especially if they have also been diagnosed with depression. Other comorbid conditions and psychosocial factors that may contribute to risk should also be considered. All children and young people who have been diagnosed with BDD should be assessed for suicidal ideation and a full risk assessment should be carried out before treatment is undertaken. If risks are identified, all professionals involved in primary and secondary care should be informed and appropriate risk management strategies put into place. Specialist mental health professionals in BDD should work in partnership with cosmetic surgeons and dermatologists to ensure that an agreed screening system is in place to accurately identify people with BDD and that agreed referral criteria have been established. They should help provide training opportunities for cosmetic surgeons and dermatologists to aid in the recognition of BDD. # Steps 3 to 5: treatment options for people with OCD or BDD Effective treatments for OCD and BDD should be offered at all levels of the healthcare system. The difference in the treatments at the higher levels will reflect increasing experience and expertise in the implementation of a limited range of therapeutic options. For many people, initial treatment may be best provided in primary care settings. However, people with more impaired functioning, higher levels of comorbidity, or poor response to initial treatment will require care from teams with greater levels of expertise and experience in the management of OCD/BDD. Irrespective of the level of care, the following recommendations should be taken into account when selecting initial treatments for people with OCD or BDD. The specific recommendations on how to provide these treatments follow in the subsequent sections. Regulatory authorities have identified that the use of selective serotonin reuptake inhibitors (SSRIs) to treat depression in children and young people may be associated with the appearance of suicidal behaviour, self‑harm or hostility, particularly at the beginning of treatment. There is no clear evidence of an increased risk of self‑harm and suicidal thoughts in young adults aged 18 years or older. But individuals mature at different rates and young adults are at a higher background risk of suicidal behaviour than older adults. Hence, young adults treated with SSRIs should be closely monitored as a precautionary measure. The Committee on Safety of Medicine's Expert Working Group on SSRIs, at a meeting in February 2005, advised that it could not be ruled out that the risk of suicidal behaviour, hostility and other adverse reactions seen in the paediatric depression trials applies to use in children or young people in all indications. Consequently, the recommendations about the use of SSRIs for people of any age with OCD or BDD have taken account of the position of regulatory authorities. ## Initial treatment options The intensity of psychological treatment has been defined as the hours of therapist input per patient. By this definition, most group treatments are defined as low intensity treatment (less than 10 hours of therapist input per patient), although each patient may receive a much greater number of hours of therapy. For guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms. In the initial treatment of adults with OCD, low intensity psychological treatments (including exposure and response prevention ; up to 10 therapist hours per patient) should be offered if the patient's degree of functional impairment is mild and/or the patient expresses a preference for a low intensity approach. Low intensity treatments include: brief individual cognitive behavioural therapy (CBT; including ERP) using structured self‑help materials brief individual CBT (including ERP) by telephone group CBT (including ERP; note, the patient may be receiving more than 10 hours of therapy in this format). Adults with OCD with mild functional impairment who are unable to engage in low intensity CBT (including ERP), or for whom low intensity treatment has proved to be inadequate, should be offered the choice of either a course of an SSRI or more intensive CBT (including ERP; more than 10 therapist hours per patient), because these treatments appear to be comparably efficacious. Adults with OCD with moderate functional impairment should be offered the choice of either a course of an SSRI or more intensive CBT (including ERP; more than 10 therapist hours per patient), because these treatments appear to be comparably efficacious. Adults with OCD with severe functional impairment should be offered combined treatment with an SSRI and CBT (including ERP). Adults with BDD with mild functional impairment should be offered a course of CBT (including ERP) that addresses key features of BDD in individual or group formats. The most appropriate format should be jointly decided by the patient and the healthcare professional. Adults with BDD with moderate functional impairment should be offered the choice of either a course of an SSRI or more intensive individual CBT (including ERP) that addresses key features of BDD. Adults with BDD with severe functional impairment should be offered combined treatment with an SSRI and CBT (including ERP) that addresses key features of BDD. For children and young people with OCD with mild functional impairment, guided self‑help may be considered in conjunction with support and information for the family or carers. Children and young people with OCD with moderate to severe functional impairment, and those with OCD with mild functional impairment for whom guided self‑help has been ineffective or refused, should be offered CBT (including ERP) that involves the family or carers and is adapted to suit the developmental age of the child as the treatment of choice. Group or individual formats should be offered depending upon the preference of the child or young person and their family or carers. All children and young people with BDD should be offered CBT (including ERP) that involves the family or carers and is adapted to suit the developmental age of the child or young person as first‑line treatment. If psychological treatment is declined by children or young people with OCD or BDD and their families or carers, or they are unable to engage in treatment, an SSRI may be considered with specific arrangements for careful monitoring for adverse events. The co‑existence of comorbid conditions, learning disorders, persisting psychosocial risk factors such as family discord, or the presence of parental mental health problems, may be factors if the child or young person's OCD or BDD is not responding to any treatment. Additional or alternative interventions for these aspects should be considered. The child or young person will still require evidence‑based treatments for his or her OCD or BDD. ## How to use psychological interventions All healthcare professionals offering psychological treatments to people of all ages with OCD or BDD should receive appropriate training in the interventions they are offering and receive ongoing clinical supervision in line with the recommendations in the Department of Health's Organising and delivering psychological therapies. For adults with obsessive thoughts who do not have overt compulsions, CBT (including exposure to obsessive thoughts and response prevention of mental rituals and neutralising strategies) should be considered. For adults with OCD, cognitive therapy adapted for OCD may be considered as an addition to ERP to enhance long‑term symptom reduction. For adults with OCD living with their family or carers, involving a family member or carer as a co‑therapist in ERP should be considered where this is appropriate and acceptable to those involved. For adults with OCD with more severe functional impairment who are housebound, unable or reluctant to attend a clinic, or have significant problems with hoarding, a period of home‑based treatment may be considered. For adults with OCD with more severe functional impairment who are housebound and unable to undertake home‑based treatment because of the nature of their symptoms (such as contamination concerns or hoarding that prevents therapists' access to the patient's home), a period of CBT by telephone may be considered. For adults with OCD who refuse or cannot engage with treatments that include ERP, individual cognitive therapy specifically adapted for OCD may be considered. When adults with OCD request forms of psychological therapy other than cognitive and/or behavioural therapies as a specific treatment for OCD (such as psychoanalysis, transactional analysis, hypnosis, marital or couple therapy) they should be informed that there is as yet no convincing evidence for a clinically important effect of these treatments. When family members or carers of people with OCD or BDD have become involved in compulsive behaviours, avoidance or reassurance seeking, treatment plans should help them reduce their involvement in these behaviours in a sensitive and supportive manner. Adults with OCD or BDD with significant functional impairment may need access to appropriate support for travel and transport to allow them to attend for their treatment. Towards the end of treatment, healthcare professionals should inform adults with OCD or BDD about how the principles learned can be applied to the same or other symptoms if they occur in the future. Psychological treatments for children and young people should be collaborative and engage the family or carers. When using psychological treatments for children or young people, healthcare professionals should consider the wider context and other professionals involved with the individual. The recommendations on the use of psychological interventions for adults may also be considered, where appropriate. In the cognitive‑behavioural treatment of children and young people with OCD or BDD, particular attention should be given to: developing and maintaining a good therapeutic alliance with the child or young person, as well as their family or carers maintaining optimism in both the child or young person and their family or carers collaboratively identifying initial and subsequent treatment targets with the child or young person actively engaging the family or carers in planning treatment and in the treatment process, especially in ERP where, if appropriate and acceptable, they may be asked to assist the child or young person encouraging the use of ERP if new or different symptoms emerge after successful treatment liaising with other professionals involved in the child or young person's life, including teachers, social workers and other healthcare professionals, especially when compulsive activity interferes with the ordinary functioning of the child or young person -ffering 1 or more additional sessions if needed at review appointments after completion of CBT. In the psychological treatment of children and young people with OCD or BDD, healthcare professionals should consider including rewards in order to enhance their motivation and reinforce desired behaviour changes. ## How to use pharmacological interventions in adults Current published evidence suggests that SSRIs are effective in treating adults with OCD or BDD, although evidence for the latter is limited and less certain. However, SSRIs may increase the risk of suicidal thoughts and self‑harm in people with depression and in younger people. It is currently unclear whether there is an increased risk for people with OCD or BDD. Regulatory authorities recommend caution in the use of SSRIs until evidence for differential safety has been demonstrated. For guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms. Starting the treatment Common concerns about taking medication for OCD or BDD should be addressed. Patients should be advised, both verbally and with written material, that: craving and tolerance do not occur there is a risk of discontinuation or withdrawal symptoms on stopping the drug, missing doses, or reducing the dose there is a range of potential side effects, including worsening anxiety, suicidal thoughts and self‑harm, which need to be carefully monitored, especially in the first few weeks of treatment there is commonly a delay in the onset of effect of up to 12 weeks, although depressive symptoms improve more quickly taking medication should not be seen as a weakness. Monitoring risk Adults with OCD or BDD started on SSRIs who are not considered to be at increased risk of suicide or self‑harm should be monitored closely and seen on an appropriate and regular basis. The arrangements for monitoring should be agreed by the patient and the healthcare professional, and recorded in the notes. Because of the potential increased risk of suicidal thoughts and self‑harm associated with the early stages of SSRI treatment, younger adults (younger than age 30 years) with OCD or BDD, or people with OCD or BDD with comorbid depression, or who are considered to be at an increased risk of suicide, should be carefully and frequently monitored by healthcare professionals. Where appropriate, other carers – as agreed by the patient and the healthcare professional – may also contribute to the monitoring until the risk is no longer considered significant. The arrangements for monitoring should be agreed by the patient and the healthcare professional, and recorded in the notes. For adults with OCD or BDD at a high risk of suicide, a limited quantity of medication should be prescribed. When adults with OCD or BDD, especially those with comorbid depression, are assessed to be at a high risk of suicide, the use of additional support such as more frequent direct contacts with primary care staff or telephone contacts should be considered, particularly during the first weeks of treatment. For adults with OCD or BDD, particularly in the initial stages of SSRI treatment, healthcare professionals should actively seek out signs of akathisia or restlessness, suicidal ideation and increased anxiety and agitation. They should also advise patients to seek help promptly if symptoms are at all distressing. Adults with OCD or BDD should be monitored around the time of dose changes for any new symptoms or worsening of their condition. For adults with OCD, the initial pharmacological treatment should be 1 of the following SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline or citalopram.Note that this is an off-label use of citalopram. See NICE's information on prescribing medicines.For guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms. For adults with BDD (including those with beliefs of delusional intensity), the initial pharmacological treatment should be fluoxetine because there is more evidence for its effectiveness in BDD than there is for other SSRIs.Note that this is an off-label use of fluoxetine. See NICE's information on prescribing medicines. In the event that an adult with OCD or BDD develops marked and/or prolonged akathisia, restlessness or agitation while taking an SSRI, the use of the drug should be reviewed. If the patient prefers, the drug should be changed to a different SSRI. Healthcare professionals should be aware of the increased risk of drug interactions when prescribing an SSRI to adults with OCD or BDD who are taking other medications. For adults with OCD or BDD, if there has been no response to a full course of treatment with an SSRI, healthcare professionals should check that the patient has taken the drug regularly and in the prescribed dose and that there is no interference from alcohol or substance use. For adults with OCD or BDD, if there has not been an adequate response to a standard dose of an SSRI, and there are no significant side effects after 4 to 6 weeks, a gradual increase in dose should be considered in line with the schedule suggested by the summary of product characteristics. For adults with OCD or BDD, the rate at which the dose of an SSRI should be increased should take into account therapeutic response, adverse effects and patient preference. Patients should be warned about, and monitored for, the emergence of side effects during dose increases. If treatment for OCD or BDD with an SSRI is effective, it should be continued for at least 12 months to prevent relapse and allow for further improvements. When an adult with OCD or BDD has taken an SSRI for 12 months after remission (symptoms are not clinically significant and the person is fully functioning for at least 12 weeks), healthcare professionals should review with the patient the need for continued treatment. This review should consider the severity and duration of the initial illness, the number of previous episodes, the presence of residual symptoms, and concurrent psychosocial difficulties. If treatment for OCD or BDD with an SSRI is continued for an extended period beyond 12 months after remission (symptoms are not clinically significant and the person is fully functioning for at least 12 weeks), the need for continuation should be reviewed at regular intervals, agreed between the patient and the prescriber, and written in the notes. For adults with OCD or BDD, to minimise discontinuation or withdrawal symptoms when reducing or stopping SSRIs, the dose should be tapered gradually over several weeks according to the person's need. The rate of reduction should take into account the starting dose, the drug half‑life and particular profiles of adverse effects. Healthcare professionals should encourage adults with OCD or BDD who are discontinuing SSRI treatment to seek advice if they experience significant discontinuation or withdrawal symptoms. The following drugs should not normally be used to treat OCD or BDD without comorbidity: tricyclic antidepressants other than clomipramine tricyclic‑related antidepressants serotonin and noradrenaline reuptake inhibitors (SNRIs), including venlafaxine monoamine oxidase inhibitors (MAOIs) anxiolytics (except cautiously for short periods to counter the early activation of SSRIs). Antipsychotics as a monotherapy should not normally be used for treating OCD. Antipsychotics as a monotherapy should not normally be used for treating BDD (including beliefs of delusional intensity). ## Poor response to initial treatment in adults If initial treatment does not result in a clinically significant improvement in both symptoms and functioning, other treatment options should be considered. When additional treatment options also fail to produce an adequate response, multidisciplinary teams with specific expertise in OCD/BDD should become involved. Their role should include supporting and collaborating with those professionals already involved in an individual's care. For guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms. For adults with OCD or BDD, if there has not been an adequate response to treatment with an SSRI alone (within 12 weeks) or CBT (including ERP) alone (more than 10 therapist hours per patient), a multidisciplinary review should be carried out. Following multidisciplinary review, for adults with OCD or BDD, if there has not been an adequate response to treatment with an SSRI alone (within 12 weeks) or CBT (including ERP) alone (more than 10 therapist hours per patient), combined treatment with CBT (including ERP) and an SSRI should be offered. For adults with OCD or BDD, if there has not been an adequate response after 12 weeks of combined treatment with CBT (including ERP) and an SSRI, or there has been no response to an SSRI alone, or the patient has not engaged with CBT, a different SSRI or clomipramine should be offered. Clomipramine should be considered in the treatment of adults with OCD or BDD after an adequate trial of at least 1 SSRI has been ineffective or poorly tolerated, if the patient prefers clomipramine or has had a previous good response to it. For adults with OCD or BDD, if there has been no response to a full trial of at least 1 SSRI alone, a full trial of combined treatment with CBT (including ERP) and an SSRI, and a full trial of clomipramine alone, the patient should be referred to a multidisciplinary team with specific expertise in the treatment of OCD/BDD for assessment and further treatment planning. The assessment of adults with OCD or BDD referred to multidisciplinary teams with specific expertise in OCD/BDD should include a comprehensive assessment of their symptom profile, previous pharmacological and psychological treatment history, adherence to prescribed medication, history of side effects, comorbid conditions such as depression, suicide risk, psychosocial stressors, relationship with family and/or carers and personality factors. Following multidisciplinary review, for adults with OCD if there has been no response to a full trial of at least 1 SSRI alone, a full trial of combined treatment with CBT (including ERP) and an SSRI, and a full trial of clomipramine alone, the following treatment options should also be considered (note, there is no evidence of the optimal sequence of the options listed below): additional CBT (including ERP) or cognitive therapy adding an antipsychotic to an SSRI or clomipramine combining clomipramine and citalopram. Note that this is an off-label use of citalopram. See NICE's information on prescribing medicines. Following multidisciplinary review, for adults with BDD, if there has been no response to a full trial of at least 1 SSRI alone, a full trial of combined treatment with CBT (including ERP) and an SSRI, and a full trial of clomipramine alone, the following treatment options should also be considered (note, there is no evidence of the optimal sequence of the options listed below): additional CBT or cognitive therapy by a different multidisciplinary team with expertise in BDD adding buspirone to an SSRI.Note that this is an off-label use of buspirone. See NICE's information on prescribing medicines. For adults with BDD, if there has been no response to treatment, or the patient is not receiving appropriate treatment, more intensive monitoring is needed because the risk of suicide is high in people with BDD. Treatments such as combined antidepressants and antipsychotic augmentation should not be routinely initiated in primary care. For guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms. For adults with OCD or BDD who are at a significant risk of suicide, healthcare professionals should only prescribe small amounts of clomipramine at a time because of its toxicity in overdose (see the summary of product characteristics for details of dosage). The patient should be monitored regularly until the risk of suicide has subsided. An electrocardiogram (ECG) should be carried out and a blood pressure measurement taken before prescribing clomipramine for adults with OCD or BDD at significant risk of cardiovascular disease. For adults with OCD or BDD, if there has not been an adequate response to the standard dose of clomipramine, and there are no significant side effects, a gradual increase in dose should be considered in line with the schedule suggested by the summary of product characteristics. For adults with OCD or BDD, treatment with clomipramine should be continued for at least 12 months if it appears to be effective and because there may be further improvement. For adults with OCD or BDD, when discontinuing clomipramine, doses should be reduced gradually in order to minimise potential discontinuation or withdrawal symptoms. ## Poor response to initial treatment in children and young people Current published evidence suggests that SSRIs are effective in treating children and young people with OCD. The only SSRIs licensed for use in children and young people with OCD are fluvoxamine and sertraline. When used as a treatment for depression, SSRIs can cause significant adverse reactions, including increased suicidal thoughts and risk of self‑harm, but it is not known whether this same risk occurs with their use in OCD. SSRIs may be safer in depression when combined with psychological treatments (see NICE's guideline on depression in children and young people). Given that the UK regulatory authority has advised that similar adverse reactions cannot be ruled out in OCD, appropriate caution should be observed, especially in the presence of comorbid depression. For a child or young person with OCD or BDD, if there has not been an adequate response within 12 weeks to a full trial of CBT (including ERP) involving the family or carers, a multidisciplinary review should be carried out. Following multidisciplinary review, for a child (aged 8 to 11 years) with OCD or BDD with moderate to severe functional impairment, if there has not been an adequate response to CBT (including ERP) involving the family or carers, the addition of an SSRI to ongoing psychological treatment may be considered. Careful monitoring should be undertaken, particularly at the beginning of treatment. Following multidisciplinary review, for a young person (aged 12 to 18 years) with OCD or BDD with moderate to severe functional impairment, if there has not been an adequate response to CBT (including ERP) involving the family or carers, the addition of an SSRI to ongoing psychological treatment should be offered. Careful monitoring should be undertaken, particularly at the beginning of treatment. For a child or a young person with OCD or BDD, if treatment with an SSRI in combination with CBT (including ERP) involving the family or carers is unsuccessful or is not tolerated because of side effects, the use of another SSRI or clomipramine with careful monitoring may be considered, especially if the child or young person has had a positive response to these alternatives in the past. This should also be in combination with CBT (including ERP). Note that this is an off-label use of clomipramine. See NICE's information on prescribing medicines. ## How to use pharmacological treatments in children and young people In adults with OCD treated by medication, there is some clinical trial evidence regarding the onset of therapeutic response, the dose needed, the rate of increase of dose, the duration of treatment and the likelihood of relapse on discontinuation. Trials of these aspects have not been done in children and/or young people, but the following good practice for prescribing SSRIs or clomipramine is based on adult trials and clinical experience. How to use SSRIs in children and young people An SSRI should only be prescribed to children and young people with OCD or BDD following assessment and diagnosis by a child and adolescent psychiatrist who should also be involved in decisions about dose changes and discontinuation. When an SSRI is prescribed to children and young people with OCD or BDD, it should be in combination with concurrent CBT (including ERP). If children and young people are unable to engage with concurrent CBT, specific arrangements should be made for careful monitoring of adverse events and these arrangements should be recorded in the notes. Children and young people with OCD or BDD starting treatment with SSRIs should be carefully and frequently monitored and seen on an appropriate and regular basis. This should be agreed by the patient, his or her family or carers and the healthcare professional, and recorded in the notes. A licensed medication (sertraline or fluvoxamine) should be used when an SSRI is prescribed to children and young people with OCD, except in patients with significant comorbid depression when fluoxetine should be used, because of current regulatory requirements. Note the uses of sertraline for under 6s, fluvoxamine for under 8s, and fluoxetine for children and young people are off-label. See NICE's information on prescribing medicines. Fluoxetine should be used when an SSRI is prescribed to children and young people with BDD. Note that this is an off-label use. See NICE's information on prescribing medicines. For children and young people with OCD or BDD who also have significant depression, the NICE recommendations for the treatment of childhood depression should be followed and there should be specific monitoring for suicidal thoughts or behaviours. See NICE's guideline on depression in children and young people. Children and young people with OCD or BDD starting treatment with SSRIs should be informed about the rationale for the drug treatment, the delay in onset of therapeutic response (up to 12 weeks), the time course of treatment, the possible side effects and the need to take the medication as prescribed. Discussion of these issues should be supplemented by written information appropriate to the needs of the child or young person and their family or carers. The starting dose of medication for children and young people with OCD or BDD should be low, especially in younger children. A half or quarter of the normal starting dose may be considered for the first week. If a lower dose of medication for children and young people with OCD or BDD is ineffective, the dose should be increased until a therapeutic response is obtained, with careful and close monitoring for adverse events. The rate of increase should be gradual and should take into account the delay in therapeutic response (up to 12 weeks) and the age of the patient. Maximum recommended doses for children and young people should not be exceeded. Children and young people prescribed an SSRI, and their families or carers, should be informed by the prescribing doctor about the possible appearance of suicidal behaviour, self‑harm or hostility, particularly at the beginning of treatment. They should be advised that if there is any sign of new symptoms of these kinds, they should make urgent contact with their medical practitioner. Where children or young people with OCD or BDD respond to treatment with an SSRI, medication should be continued for at least 6 months post‑remission (that is, symptoms are not clinically significant and the child or young person is fully functioning for at least 12 weeks). Children and young people with OCD or BDD and their families or carers should be advised about the possible side effects of clomipramine, including toxicity in overdose. Before starting treatment with clomipramine in children and young people with OCD or BDD, an ECG should be carried out to exclude cardiac conduction abnormalities. For a child or young person with OCD or BDD, if there has not been an adequate response to the standard dose of clomipramine, and there are no significant side effects, a gradual increase in dose may be cautiously considered. Treatment of a child or young person with OCD or BDD with clomipramine should be continued for at least 6 months if the treatment appears to be effective, because there may be further improvement in symptoms. In children and young people with OCD or BDD, an attempt should be made to withdraw medication if remission has been achieved (that is, symptoms are no longer clinically significant and the child or young person is fully functioning) and maintained for at least 6 months, and if that is their wish. Patients and their family or carers should be warned that relapse and/or discontinuation or withdrawal symptoms may occur. They should be advised to contact their medical practitioner should symptoms of discontinuation or withdrawal arise. For children and young people with OCD or BDD, to minimise discontinuation or withdrawal symptoms on reducing or stopping antidepressants, particularly SSRIs, the dose should be tapered gradually over several weeks according to the individual's need. The rate of reduction should take into account the starting dose, the drug half‑life and particular profiles of adverse effects. Children and young people with OCD or BDD should continue with psychological treatment throughout the period of drug discontinuation because this may reduce the risk of relapse. Tricyclic antidepressants other than clomipramine should not be used to treat OCD or BDD in children and young people. Other antidepressants (MAOIs, SNRIs) should not be used to treat OCD or BDD in children and young people. Antipsychotics should not be used alone in the routine treatment of OCD or BDD in children or young people, but may be considered as an augmentation strategy. # Step 6: intensive treatment and inpatient services for people with OCD or BDD People with severe, chronic, treatment‑refractory OCD or BDD should have continuing access to specialist treatment services staffed by multidisciplinary teams of healthcare professionals with expertise in the management of the disorders. Inpatient services, with specific expertise in OCD and BDD, are appropriate for a small proportion of people with these disorders, and may be considered when: there is risk to life there is severe self‑neglect there is extreme distress or functional impairment there has been no response to adequate trials of pharmacological, psychological or combined treatments over long periods of time in other settings a person has additional diagnoses, such as severe depression, anorexia nervosa or schizophrenia, that make outpatient treatment more complex a person has a reversal of normal night or day patterns that make attendance at any daytime therapy impossible the compulsions and avoidance behaviour are so severe or habitual that they cannot undertake normal activities of daily living. A small minority of adults with long‑standing and disabling obsessive‑compulsive symptoms that interfere with daily living and have prevented them from developing a normal level of autonomy may, in addition to treatment, need suitable accommodation in a supportive environment that will enable them to develop life skills for independent living. Neurosurgery is not recommended in the treatment of OCD. However, if a patient requests neurosurgery because they have severe OCD that is refractory to other forms of treatment, the following should be taken into consideration. Existing published criteria (such as Matthews and Eljamel's Status of neurosurgery for mental disorder in Scotland) should be used to guide decisions about suitability. Multidisciplinary teams with a high degree of expertise in the pharmacological and psychological treatment of OCD should have been recently involved in the patient's care. All pharmacological options should have been considered and every attempt should have been made to engage the individual in CBT (including ERP) and cognitive therapy, including very intensive and/or inpatient treatments. Standardised assessment protocols should be used pre‑ and post‑operation and at medium‑ and long‑term follow‑ups in order to audit the interventions. These assessment protocols should include standardised measures of symptoms, quality of life, social and personality function, as well as comprehensive neuropsychological tests. Services offering assessment for neurosurgical treatments should have access to independent advice on issues such as adequacy of previous treatment and consent and should be subject to appropriate oversight. Post‑operative care should be carefully considered, including pharmacological and psychological therapies. Services offering assessment for neurosurgical treatments should be committed to sharing and publishing audit information. For children and young people with severe OCD or BDD with high levels of distress and/or functional impairment, if there has been no response to adequate treatment in outpatient settings, or there is significant self‑neglect or risk of suicide, assessment for intensive inpatient treatment in units where specialist treatment for children or young people with OCD or BDD is available should be offered. # Discharge after recovery When a person of any age with OCD or BDD is in remission (symptoms are not clinically significant and the person is fully functioning for 12 weeks), he or she should be reviewed regularly for 12 months by a mental health professional. The exact frequency of contact should be agreed between the professional and the person with OCD or BDD and/or the family and/or carer and recorded in the notes. At the end of the 12‑month period if recovery is maintained the person can be discharged to primary care. OCD and BDD can have a fluctuating or episodic course, or relapse may occur after successful treatment. Therefore, people who have been successfully treated and discharged should be seen as soon as possible if re‑referred with further occurrences of OCD or BDD, rather than placed on a routine waiting list. For those in whom there has been no response to treatment, care coordination (or other suitable processes) should be used at the end of any specific treatment programme to identify any need for continuing support and appropriate services to address it.# Recommendations for research The Guideline Development Group has made the following recommendations for research, on the basis of its review of the evidence. The Group regards these recommendations as the most important research areas to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of recommendations for research is detailed in the full guideline. # Treatment of OCD and BDD among young people and young adults Appropriately blinded randomised controlled trials (RCTs) should be conducted to assess the acute and long‑term efficacy (including measures of social function and quality of life), acceptability and the cost effectiveness of cognitive behavioural therapy (CBT) and selective serotonin re uptake inhibitors (SSRIs), alone and in combination, compared with each other and with appropriate control treatments for both the psychological and pharmacological arms. These should be carried out in a broadly based sample of young people and young adults (for example, aged 12 to 25 years) diagnosed with obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) across a range of functional impairment (using minimal exclusion criteria). The trials should be powered to examine the effect of treatment for combined versus single‑strand treatments and involve a follow‑up of 1, 2 and 5 years. Any treatment received in the follow‑up period should also be recorded. # CBT treatment intensity formats among adults with OCD Appropriately blinded RCTs should be conducted to assess the efficacy (including measures of social function and quality of life), acceptability and the cost effectiveness of different delivery formats of CBT that include exposure and response prevention (ERP) for adults with OCD, including brief individual CBT using structured self‑help materials, brief individual CBT by telephone, group CBT and standard individual CBT compared with each other and with credible psychological treatment that is not specific to OCD and BDD (such as anxiety management training) in a broadly based sample of people diagnosed with OCD across a range of functional impairment (using minimal exclusion criteria). The trials should be powered to examine the effect of treatment in different bands of severity or functional impairment and involve a follow‑up of 1 and 2 years. Any treatment received in the follow‑up period should also be recorded. # CBT for adults with OCD who have not responded to treatment An appropriately blinded RCT should be conducted to assess the efficacy (including measures of social functioning and quality of life as well as OCD) of intensive versus spaced individual treatments (that include both ERP and cognitive therapy elements) compared with a treatment‑as‑usual control in a broadly based sample of adults diagnosed with OCD who have not responded to 1 or more adequate trials of an SSRI or clomipramine and 1 or more trials of CBT (that included ERP). The trial should be powered to examine the relative efficacy of intensive versus spaced treatment and involve a follow‑up of 1 and 2 years. Any treatment received in the follow‑up period should also be recorded. # Screening for OCD and BDD Appropriately designed studies should be conducted to compare validated screening instruments for the detection of OCD and BDD in children, young people and adults. An emphasis should be placed on examining those that use computer technology and more age‑appropriate methods of assessing both symptoms and functioning, taking into account cultural and ethnic variations in communication, and family values. For BDD, specific populations would include young people or adults who consult in dermatology or plastic surgery and those with other psychiatric disorders. # CBT for children and young people with OCD and BDD An appropriately blinded RCT should be conducted to assess the efficacy (including measures of social functioning and quality of life) and the cost effectiveness of individual CBT and CBT involving the family or carers compared with each other and with a credible psychological treatment that is not specific to OCD and BDD (such as anxiety management training) in a broadly based sample of children and young people diagnosed with OCD and BDD (using minimal exclusion criteria). The trial should be powered to examine the effect of treatment in children and young people separately and involve a follow‑up of at least 1 year.# Appendix A: Grading scheme All evidence was classified according to an accepted hierarchy of evidence that was originally adapted from the US Agency for Healthcare Policy and Research Classification (see table 1). Recommendations were then graded A to C based on the level of associated evidence. This grading scheme is based on a scheme formulated by the Clinical Outcomes Group of the NHS Executive (1996). Level Type of evidence Grade Evidence Evidence obtained from a single randomised controlled trial or a meta‑analysis of randomised controlled trials A At least 1 randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation (evidence level 1) without extrapolation a Evidence obtained from at least 1 well‑designed controlled study without randomisation B Well‑conducted clinical studies but no randomised clinical trials on the topic of recommendation (evidence levels 2 or 3); or extrapolated from level 1 evidence b Evidence obtained from at least 1 other well‑designed quasi-experimental study Evidence obtained from well‑designed non‑experimental descriptive studies, such as comparative studies, correlation studies and case studies Evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities C Expert committee reports or opinions and/or clinical experiences of respected authorities (evidence level 4) or extrapolated from level 1 or 2 evidence. This grading indicates that directly applicable clinical studies of good quality are absent or not readily available Evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities GPP Recommended good practice based on the clinical experience of the GDG. Adapted from Eccles M, Mason J (2001) How to develop cost‑conscious guidelines. Health Technology Assessment 5:16 and Mann T (1996) Clinical Guidelines: Using Clinical Guidelines to Improve Patient Care Within the NHS. London: Department of Health.# Appendix D: Technical detail on the criteria for audit # Possible objectives for an audit One or more audits could be carried out in different care settings to ensure that: individuals with obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) are involved in their care treatment options are appropriately offered and provided for individuals with OCD or BDD. # People that could be included in an audit and time period for selection A single audit could include all individuals with OCD or BDD. Alternatively, individual audits could be undertaken on specific groups of individuals such as: people with OCD or BDD at a particular stage (for example, to study assessment) a sample of people with OCD or BDD from particular populations in primary care. # Measures that could be used as a basis for an audit Please see tables below. Criterion Exception Definition of terms Each primary care trust, mental healthcare trust, and children's trust that provides mental health services has access to a specialist multidisciplinary obsessive-compulsive disorder (OCD)/body dysmorphic disorder (BDD) team. a) Operational policies in each primary care trust, mental healthcare trust and children's trust that provides mental health services specify procedure for accessing specialist OCD/BDD team b) Specialist teams offer a liaison function to other mental health professionals None A specialist OCD/BDD team is able to conduct expert assessment, specialist cognitive‑behavioural and pharmacological treatment and provide age‑appropriate care A liaison function will aim to: increase skills in the assessment and evidence‑based treatment of people with OCD or BDD; provide high‑quality advice; aid understanding of the needs of family or carers and developmental needs Criterion Exception Definition of terms People with obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) who have relapsed following successful treatment are seen by a healthcare professional as soon as possible if re‑referred, and where there has been no response to treatment are appropriately supported. a) Operational policies indicate the re‑referral pathway b) Operational policies indicate that care coordination or other suitable process is followed for people where there has been no response to treatment Person with OCD or BDD refuses re‑referral None Criterion Exception Definition of terms In their initial treatment, adults who have mild obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD), or those who express a preference, are offered a low intensity psychological treatment. a) Clinical notes indicate that people are informed of low intensity treatment options b) Clinical notes indicate the clinical outcome of low intensity interventions Adults with moderate to severe OCD or BDD Children and young people Adults who refuse this treatment Low intensity treatments (less than 10 therapist hours) include: brief individual cognitive behavioural therapy (CBT; including ERP ) using structured self‑help materials brief individual CBT (including ERP) by telephone group CBT (including ERP) – note the patient may be receiving more than 10 hours of therapy in this format Criterion Exception Definition of terms Where adults have been unable to engage with low intensity treatment, or there has been no response to low intensity treatment, adults with mild obsessive-compulsive disorder (OCD) are offered more intensive treatment interventions. a) Clinical notes indicate that people have been informed of the possibility of intensive cognitive behavioural therapy (CBT; including ERP ) or a selective serotonin reuptake inhibitor (SSRI) b) Clinical notes indicate the clinical outcome of the intervention offered Adults where there is improvement with low intensity interventions Children and young people Adults who refuse these treatments More intensive treatment interventions include: a choice of either a course of an SSRI, or more intensive CBT (including ERP; of more than 10 therapist hours per patient) Criterion Exception Definition of terms Adults who have obsessive-compulsive disorder (OCD) with moderate functional impairment are offered the choice of either a course of a selective serotonin reuptake inhibitor (SSRI) or more intensive cognitive behavioural therapy (CBT; including ERP ). a) Clinical notes indicate that people have been informed of the possibility of more intensive CBT (including ERP) or an SSRI b) Clinical notes indicate the clinical outcome of the intervention offered Children and young people More intensive CBT (including ERP) means: more than 10 therapist hours per patient Criterion Exception Definition of terms Adults who have moderate body dysmorphic disorder (BDD) are offered the choice of a selective serotonin reuptake inhibitor (SSRI) or more intensive individual cognitive behavioural therapy (CBT; including ERP) or an SSRI. a) Clinical notes indicate that people have been informed of the possibility of intensive individual CBT (including ERP ) or an SSRI b) Clinical notes indicate the clinical outcome of the intervention offered Children and young people CBT (including ERP) means: ERP that addresses key features of BDD. Criterion Exception Definition of terms Children and young people who have obsessive-compulsive disorder (OCD) with moderate or severe impairment or those with mild impairment where there is no response to guided self‑help, or where guided self‑help has been refused, will be offered cognitive behavioural therapy (CBT; including ERP ) as the treatment of choice. a) Clinical notes indicate that the child or young person and the family or carer were informed of possibility of CBT b) Clinical notes identify the clinical outcome of CBT Children and young people who refuse CBT (including ERP) CBT (including ERP) means: treatment involving the family or carers and adapted to suit the developmental age of the child. Group or individual formats should be offered depending upon the preference of the child or young person and their family or carers Criterion Exception Definition of terms Children who have obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) where there has not been an adequate response to cognitive behavioural therapy (CBT; including ERP ) attend a multidisciplinary review (with family or carers) where the use of a selective serotonin reuptake inhibitor (SSRI) is considered in addition to ongoing psychological treatment. a) Clinical notes indicate a multidisciplinary review occurred and identified that the use of an SSRI in addition to ongoing psychological treatment was explored in detail b) Clinical notes indicate that careful monitoring was carried out c) Clinical notes indicate the clinical outcome of the intervention offered Children who respond to CBT (including ERP) Children: aged 8 to 11 years Careful monitoring: being seen frequently on an appropriate and regular basis agreed by the patient, his or her family or carers and the healthcare professional, and recorded in the notes Criterion Exception Definition of terms Young people who have obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) where there has not been an adequate response to cognitive behavioural therapy (CBT; including ERP ) attend a multidisciplinary review (with family or carers) where the use of a selective serotonin reuptake inhibitor (SSRI) is considered in addition to ongoing psychological treatment a) Clinical notes indicate a multidisciplinary review occurred and identified that the use of an SSRI in addition to ongoing psychological treatment was explored in detail b) Clinical notes indicate that careful monitoring was carried out c) Clinical notes indicate the clinical outcome of the intervention offered Young people who respond to CBT (including ERP) Young people: aged 12 to 18 years Careful monitoring: being seen frequently on an appropriate and regular basis agreed by the patient, his or her family or carers and the healthcare professional, and recorded in the notes Criterion Exception Definition of terms Children and young people with body dysmorphic disorder (BDD) are considered for cognitive behavioural therapy (CBT; including ERP ) as first‑line treatment. a) Clinical notes indicate that the healthcare professional responsible has discussed the need for CBT (including ERP) and an arrangement has been made b) Clinical notes indicate the clinical outcome of the intervention offered Children or young people who refuse treatment Children: aged 8 to 11 years. Young people: aged 12 to 18 years. CBT (including ERP) means: involving the family or carers and adapted to the developmental age of the child or young person	{'Introduction': "Obsessive‑compulsive disorder (OCD) is characterised by the presence of either obsessions or compulsions, but commonly both. The symptoms can cause significant functional impairment and/or distress. An obsession is defined as an unwanted intrusive thought, image or urge that repeatedly enters the person's mind. Compulsions are repetitive behaviours or mental acts that the person feels driven to perform. A compulsion can either be overt and observable by others, such as checking that a door is locked, or a covert mental act that cannot be observed, such as repeating a certain phrase in one's mind.\n\nIt is thought that 1% to 2% of the population have OCD, although some studies have estimated 2% to 3%.\n\nBody dysmorphic disorder (BDD) is characterised by a preoccupation with an imagined defect in one's appearance, or in the case of a slight physical anomaly, the person's concern is markedly excessive. BDD is characterised by time‑consuming behaviours such as mirror gazing, comparing particular features to those of others, excessive camouflaging tactics to hide the defect, skin picking and reassurance seeking.\n\nIt is thought that 0.5% to 0.7% of the population have BDD.\n\nThe recommendations in this guideline were graded according to the quality of the evidence they were based on. The gradings are available in the full guideline and are not shown in this web version.", 'Recommendations': "People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care.\n\nMaking decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.\n\n# Principles of care for all people with OCD or BDD and their families or carers\n\n## Understanding\n\nPeople with obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) are often ashamed and embarrassed by their condition and may find it very difficult to discuss their symptoms with healthcare professionals, friends, family or carers. Healthcare professionals should help patients, and their families or carers where appropriate, to understand the involuntary nature of the symptoms by providing accurate information in an appropriate format on current understanding of the disorders from psychological and/or biological perspectives.\n\nWhen assessing people with OCD or BDD, healthcare professionals should sensitively explore the hidden distress and disability commonly associated with the disorders, providing explanation and information wherever necessary. In particular, people with OCD who are distressed by their obsessive thoughts should be informed that such thoughts are occasionally experienced by almost everybody, and when frequent and distressing are a typical feature of OCD.\n\n## Continuity of care\n\nOCD and BDD are frequently recurring or chronic conditions that often affect some of the most intimate aspects of a person's life. Healthcare professionals should therefore ensure continuity of care and minimise the need for multiple assessments by different healthcare professionals.\n\nBecause OCD and BDD may occur across a person's lifespan, particular care should be given to the provision of appropriate care at all ages and a seamless transition between services aimed at specific ages, such as the transition from services for young people to services for adults.\n\nCareful consideration should be given to the effective integration and coordination of care of people with OCD and BDD across both primary and secondary care. There should be clear, written agreement among individual healthcare professionals about the responsibility for monitoring and treating people with OCD and BDD. A written copy of this agreement should be given to the patient. This should be in collaboration with the patient, and where appropriate:\n\nthe Care Programme Approach (CPA) should be used\n\nthe patient's family or carers should be involved\n\nhealthcare professionals should liaise with other professionals involved in providing care and support to the patient.\n\n## Information and support\n\nTreatment and care should take into account the individual needs and preferences of people with OCD or BDD. Patients should have the opportunity to make informed decisions about their care and treatment. Where patients do not have the capacity to make decisions, or children or young people are not old enough to do so, healthcare professionals should follow the\xa0Department of Health's Reference guide to consent for examination or treatment.\n\nGood communication between healthcare professionals and people with OCD or BDD is essential. Provision of information, treatment and care should be tailored to the needs of the individual, culturally appropriate, and provided in a form that is accessible to people who have additional needs, such as learning difficulties, physical or sensory disabilities, or limited competence in speaking or reading English.\n\nHealthcare professionals should consider informing people with OCD or BDD and their family or carers about local self‑help and support groups, and encourage them to participate in such groups where appropriate.\n\n## Religion and culture\n\nObsessive‑compulsive symptoms may sometimes involve a person's religion, such as religious obsessions and scrupulosity, or cultural practices. When the boundary between religious or cultural practice and obsessive‑compulsive symptoms is unclear, healthcare professionals should, with the patient's consent, consider seeking the advice and support of an appropriate religious or community leader to support the therapeutic process.\n\n## Families and carers\n\nBecause OCD and BDD often have an impact on families and carers, healthcare professionals should promote a collaborative approach with people with OCD or BDD and their family or carers, wherever this is appropriate and possible.\n\nIn the treatment and care of people with OCD or BDD, family members or carers should be provided with good information (both verbal and written) about the disorder, its likely causes, its course and its treatment.\n\nAssessment and treatment plans for people with OCD or BDD should, where appropriate, involve relevant family members or carers. In some cases, particularly with children and young people, when the symptoms of OCD or BDD interfere with academic or workplace performance, it may be appropriate to liaise with professionals from these organisations. Assessment should include the impact of rituals and compulsions on others (in particular on dependent children) and the degree to which carers are involved in supporting or carrying out behaviours related to the disorder.\n\nIf dependent children are considered to be at risk of emotional, social or mental health problems as a result of the behaviour of a parent with OCD or BDD and/or the child's involvement in related activity, independent assessment of the child should be requested. If this is carried out, the parent should be kept informed at every stage of the assessment.\n\nIn the treatment of people with OCD or BDD, especially when the disorder is moderate to severe or chronic, an assessment of their carer's social, occupational and mental health needs should be offered. See NICE's guideline on supporting adult carers.\n\n# Stepped care for adults, young people and children with OCD or BDD\n\nThe stepped‑care model draws attention to the different needs of people with OCD and BDD, depending on the characteristics of their disorder, their personal and social circumstances, their age, and the responses that are required from services. It provides a framework in which to organise the provision of services in order to identify and access the most effective interventions (see figure 1).\n\n## Figure 1 The stepped-care model\n\nThe full guideline contains figure 1.\n\nStepped care attempts to provide the most effective but least intrusive treatments appropriate to a person's needs. It assumes that the course of the disorder is monitored and referral to the appropriate level of care is made depending on the person's difficulties. Each step introduces additional interventions; the higher steps normally assume interventions in the previous step have been offered and/or attempted, but there are situations where an individual may be referred to any appropriate level. The guidance follows the steps in the figure.\n\nAt all stages of assessment and treatment, families or carers should be involved as appropriate. This is particularly important in the treatment of children and young people with OCD or BDD where it may also be helpful to involve others in their network, for example teachers, school health advisors, educational psychologists, and educational social workers.\n\n# Step 1: awareness and recognition\n\nAlthough the more common forms of OCD are likely to be recognised when people report symptoms, less common forms of OCD and many cases of BDD may remain unrecognised, sometimes for many years. Relatively few mental health professionals or GPs have expertise in the recognition, assessment, diagnosis and treatment of the less common forms of OCD and BDD.\n\nEach primary care trust, mental healthcare trust and children's trust that provides mental health services should have access to a specialist OCD/BDD multidisciplinary team offering age‑appropriate care. This team would perform the following functions: increase the skills of mental health professionals in the assessment and evidence‑based treatment of people with OCD or BDD, provide high‑quality advice, understand family and developmental needs, and, when appropriate, conduct expert assessment and specialist cognitive‑behavioural and pharmacological treatment.\n\nSpecialist mental healthcare professionals in OCD or BDD should collaborate with local and national voluntary organisations to increase awareness and understanding of the disorders and improve access to high‑quality information about them. Such information should also be made available to primary and secondary healthcare professionals, and to professionals from other public services who may come into contact with people of any age with OCD or\xa0BDD.\n\nSpecialist OCD/BDD teams should collaborate with people with OCD or BDD and their families or carers to provide training for all mental health professionals, cosmetic surgeons and dermatology professionals.\n\n# Step 2: recognition and assessment\n\n## OCD\n\nFor people known to be at higher risk of OCD (such as individuals with symptoms of depression, anxiety, alcohol or substance misuse, BDD or an eating disorder), or for people attending dermatology clinics, healthcare professionals should routinely consider and explore the possibility of comorbid OCD by asking direct questions about possible symptoms such as the following.\n\nDo you wash or clean a lot?\n\nDo you check things a lot?\n\nIs there any thought that keeps bothering you that you would like to get rid of but cannot?\n\nDo your daily activities take a long time to finish?\n\nAre you concerned about putting things in a special order or are you very upset by mess?\n\nDo these problems trouble you?\n\nIn people who have been diagnosed with OCD, healthcare professionals should assess the risk of self‑harm and suicide, especially if they have also been diagnosed with depression. Part of the risk assessment should include the impact of their compulsive behaviours on themselves or others. Other comorbid conditions and psychosocial factors that may contribute to risk should also be considered.\n\nIf healthcare professionals are uncertain about the risks associated with intrusive sexual, aggressive or death‑related thoughts reported by people with OCD, they should consult mental health professionals with specific expertise in the assessment and management of OCD. These themes are common in people with OCD at any age, and are often misinterpreted as indicating risk.\n\n## BDD\n\nFor people known to be at higher risk of BDD (such as individuals with symptoms of depression, social phobia, alcohol or substance misuse, OCD or an eating disorder), or for people with mild disfigurements or blemishes who are seeking a cosmetic or dermatological procedure, healthcare professionals should routinely consider and explore the possibility of BDD.\n\nIn the assessment of people at higher risk of BDD, the following 5\xa0questions should be asked to help identify individuals with BDD.\n\nDo you worry a lot about the way you look and wish you could think about it less?\n\nWhat specific concerns do you have about your appearance?\n\nOn a typical day, how many hours a day is your appearance on your mind? (More than 1\xa0hour a day is considered excessive.)\n\nWhat effect does it have on your life?\n\nDoes it make it hard to do your work or be with friends?\n\nPeople with suspected or diagnosed BDD seeking cosmetic surgery or dermatological treatment should be assessed by a mental health professional with specific expertise in the management of BDD.\n\nIn people who have been diagnosed with BDD, healthcare professionals should assess the risk of self‑harm and suicide, especially if they have also been diagnosed with depression. Other comorbid conditions and psychosocial factors that may contribute to risk should also be considered.\n\nAll children and young people who have been diagnosed with BDD should be assessed for suicidal ideation and a full risk assessment should be carried out before treatment is undertaken. If risks are identified, all professionals involved in primary and secondary care should be informed and appropriate risk management strategies put into place.\n\nSpecialist mental health professionals in BDD should work in partnership with cosmetic surgeons and dermatologists to ensure that an agreed screening system is in place to accurately identify people with BDD and that agreed referral criteria have been established. They should help provide training opportunities for cosmetic surgeons and dermatologists to aid in the recognition of BDD.\n\n# Steps 3 to 5: treatment options for people with OCD or BDD\n\nEffective treatments for OCD and BDD should be offered at all levels of the healthcare system. The difference in the treatments at the higher levels will reflect increasing experience and expertise in the implementation of a limited range of therapeutic options. For many people, initial treatment may be best provided in primary care settings. However, people with more impaired functioning, higher levels of comorbidity, or poor response to initial treatment will require care from teams with greater levels of expertise and experience in the management of OCD/BDD.\n\nIrrespective of the level of care, the following recommendations should be taken into account when selecting initial treatments for people with OCD or BDD. The specific recommendations on how to provide these treatments follow in the subsequent sections.\n\nRegulatory authorities have identified that the use of selective serotonin reuptake inhibitors (SSRIs) to treat depression in children and young people may be associated with the appearance of suicidal behaviour, self‑harm or hostility, particularly at the beginning of treatment. There is no clear evidence of an increased risk of self‑harm and suicidal thoughts in young adults aged 18\xa0years or older. But individuals mature at different rates and young adults are at a higher background risk of suicidal behaviour than older adults. Hence, young adults treated with SSRIs should be closely monitored as a precautionary measure. The Committee on Safety of Medicine's Expert Working Group on SSRIs, at a meeting in February 2005, advised that it could not be ruled out that the risk of suicidal behaviour, hostility and other adverse reactions seen in the paediatric depression trials applies to use in children or young people in all indications. Consequently, the recommendations about the use of SSRIs for people of any age with OCD or BDD have taken account of the position of regulatory authorities.\n\n## Initial treatment options\n\nThe intensity of psychological treatment has been defined as the hours of therapist input per patient. By this definition, most group treatments are defined as low intensity treatment (less than 10\xa0hours of therapist input per patient), although each patient may receive a much greater number of hours of therapy.\n\nFor guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.\n\nIn the initial treatment of adults with OCD, low intensity psychological treatments (including exposure and response prevention [ERP]; up to 10 therapist hours per patient) should be offered if the patient's degree of functional impairment is mild and/or the patient expresses a preference for a low intensity approach. Low intensity treatments include:\n\nbrief individual cognitive behavioural therapy (CBT; including ERP) using structured self‑help materials\n\nbrief individual CBT (including ERP) by telephone\n\ngroup CBT (including ERP; note, the patient may be receiving more than 10\xa0hours of therapy in this format).\n\nAdults with OCD with mild functional impairment who are unable to engage in low intensity CBT (including ERP), or for whom low intensity treatment has proved to be inadequate, should be offered the choice of either a course of an SSRI or more intensive CBT (including ERP; more than 10 therapist hours per patient), because these treatments appear to be comparably efficacious.\n\nAdults with OCD with moderate functional impairment should be offered the choice of either a course of an SSRI or more intensive CBT (including ERP; more than 10 therapist hours per patient), because these treatments appear to be comparably efficacious.\n\nAdults with OCD with severe functional impairment should be offered combined treatment with an SSRI and CBT (including ERP).\n\nAdults with BDD with mild functional impairment should be offered a course of CBT (including ERP) that addresses key features of BDD in individual or group formats. The most appropriate format should be jointly decided by the patient and the healthcare professional.\n\nAdults with BDD with moderate functional impairment should be offered the choice of either a course of an SSRI or more intensive individual CBT (including ERP) that addresses key features of BDD.\n\nAdults with BDD with severe functional impairment should be offered combined treatment with an SSRI and CBT (including ERP) that addresses key features of BDD.\n\nFor children and young people with OCD with mild functional impairment, guided self‑help may be considered in conjunction with support and information for the family or carers.\n\nChildren and young people with OCD with moderate to severe functional impairment, and those with OCD with mild functional impairment for whom guided self‑help has been ineffective or refused, should be offered CBT (including ERP) that involves the family or carers and is adapted to suit the developmental age of the child as the treatment of choice. Group or individual formats should be offered depending upon the preference of the child or young person and their family or carers.\n\nAll children and young people with BDD should be offered CBT (including ERP) that involves the family or carers and is adapted to suit the developmental age of the child or young person as first‑line treatment.\n\nIf psychological treatment is declined by children or young people with OCD or BDD and their families or carers, or they are unable to engage in treatment, an SSRI may be considered with specific arrangements for careful monitoring for adverse events.\n\nThe co‑existence of comorbid conditions, learning disorders, persisting psychosocial risk factors such as family discord, or the presence of parental mental health problems, may be factors if the child or young person's OCD or BDD is not responding to any treatment. Additional or alternative interventions for these aspects should be considered. The child or young person will still require evidence‑based treatments for his or her OCD or BDD.\n\n## How to use psychological interventions\n\nAll healthcare professionals offering psychological treatments to people of all ages with OCD or BDD should receive appropriate training in the interventions they are offering and receive ongoing clinical supervision in line with the recommendations in the Department of Health's Organising and delivering psychological therapies.\n\nFor adults with obsessive thoughts who do not have overt compulsions, CBT (including exposure to obsessive thoughts and response prevention of mental rituals and neutralising strategies) should be considered.\n\nFor adults with OCD, cognitive therapy adapted for OCD may be considered as an addition to ERP to enhance long‑term symptom reduction.\n\nFor adults with OCD living with their family or carers, involving a family member or carer as a co‑therapist in ERP should be considered where this is appropriate and acceptable to those involved.\n\nFor adults with OCD with more severe functional impairment who are housebound, unable or reluctant to attend a clinic, or have significant problems with hoarding, a period of home‑based treatment may be considered.\n\nFor adults with OCD with more severe functional impairment who are housebound and unable to undertake home‑based treatment because of the nature of their symptoms (such as contamination concerns or hoarding that prevents therapists' access to the patient's home), a period of CBT by telephone may be considered.\n\nFor adults with OCD who refuse or cannot engage with treatments that include ERP, individual cognitive therapy specifically adapted for OCD may be considered.\n\nWhen adults with OCD request forms of psychological therapy other than cognitive and/or behavioural therapies as a specific treatment for OCD (such as psychoanalysis, transactional analysis, hypnosis, marital or couple therapy) they should be informed that there is as yet no convincing evidence for a clinically important effect of these treatments.\n\nWhen family members or carers of people with OCD or BDD have become involved in compulsive behaviours, avoidance or reassurance seeking, treatment plans should help them reduce their involvement in these behaviours in a sensitive and supportive manner.\n\nAdults with OCD or BDD with significant functional impairment may need access to appropriate support for travel and transport to allow them to attend for their treatment.\n\nTowards the end of treatment, healthcare professionals should inform adults with OCD or BDD about how the principles learned can be applied to the same or other symptoms if they occur in the future.\n\nPsychological treatments for children and young people should be collaborative and engage the family or carers. When using psychological treatments for children or young people, healthcare professionals should consider the wider context and other professionals involved with the individual. The recommendations on the use of psychological interventions for adults may also be considered, where appropriate.\n\nIn the cognitive‑behavioural treatment of children and young people with OCD or BDD, particular attention should be given to:\n\ndeveloping and maintaining a good therapeutic alliance with the child or young person, as well as their family or carers\n\nmaintaining optimism in both the child or young person and their family or carers\n\ncollaboratively identifying initial and subsequent treatment targets with the child or young person\n\nactively engaging the family or carers in planning treatment and in the treatment process, especially in ERP where, if appropriate and acceptable, they may be asked to assist the child or young person\n\nencouraging the use of ERP if new or different symptoms emerge after successful treatment\n\nliaising with other professionals involved in the child or young person's life, including teachers, social workers and other healthcare professionals, especially when compulsive activity interferes with the ordinary functioning of the child or young person\n\noffering 1\xa0or more additional sessions if needed at review appointments after completion of CBT.\n\nIn the psychological treatment of children and young people with OCD or BDD, healthcare professionals should consider including rewards in order to enhance their motivation and reinforce desired behaviour changes.\n\n## How to use pharmacological interventions in adults\n\nCurrent published evidence suggests that SSRIs are effective in treating adults with OCD or BDD, although evidence for the latter is limited and less certain. However, SSRIs may increase the risk of suicidal thoughts and self‑harm in people with depression and in younger people. It is currently unclear whether there is an increased risk for people with OCD or BDD. Regulatory authorities recommend caution in the use of SSRIs until evidence for differential safety has been demonstrated.\n\nFor guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.\n\nStarting the treatment\n\nCommon concerns about taking medication for OCD or BDD should be addressed. Patients should be advised, both verbally and with written material, that:\n\ncraving and tolerance do not occur\n\nthere is a risk of discontinuation or withdrawal symptoms on stopping the drug, missing doses, or reducing the dose\n\nthere is a range of potential side effects, including worsening anxiety, suicidal thoughts and self‑harm, which need to be carefully monitored, especially in the first few weeks of treatment\n\nthere is commonly a delay in the onset of effect of up to 12\xa0weeks, although depressive symptoms improve more quickly\n\ntaking medication should not be seen as a weakness.\n\nMonitoring risk\n\nAdults with OCD or BDD started on SSRIs who are not considered to be at increased risk of suicide or self‑harm should be monitored closely and seen on an appropriate and regular basis. The arrangements for monitoring should be agreed by the patient and the healthcare professional, and recorded in the notes.\n\nBecause of the potential increased risk of suicidal thoughts and self‑harm associated with the early stages of SSRI treatment, younger adults (younger than age 30\xa0years) with OCD or BDD, or people with OCD or BDD with comorbid depression, or who are considered to be at an increased risk of suicide, should be carefully and frequently monitored by healthcare professionals. Where appropriate, other carers – as agreed by the patient and the healthcare professional – may also contribute to the monitoring until the risk is no longer considered significant. The arrangements for monitoring should be agreed by the patient and the healthcare professional, and recorded in the notes.\n\nFor adults with OCD or BDD at a high risk of suicide, a limited quantity of medication should be prescribed.\n\nWhen adults with OCD or BDD, especially those with comorbid depression, are assessed to be at a high risk of suicide, the use of additional support such as more frequent direct contacts with primary care staff or telephone contacts should be considered, particularly during the first weeks of treatment.\n\nFor adults with OCD or BDD, particularly in the initial stages of SSRI treatment, healthcare professionals should actively seek out signs of akathisia or restlessness, suicidal ideation and increased anxiety and agitation. They should also advise patients to seek help promptly if symptoms are at all distressing.\n\nAdults with OCD or BDD should be monitored around the time of dose changes for any new symptoms or worsening of their condition.\n\nFor adults with OCD, the initial pharmacological treatment should be 1\xa0of the following SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline or citalopram.Note that this is an off-label use of citalopram. See NICE's information on prescribing medicines.For guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.\n\nFor adults with BDD (including those with beliefs of delusional intensity), the initial pharmacological treatment should be fluoxetine because there is more evidence for its effectiveness in BDD than there is for other SSRIs.Note that this is an off-label use of fluoxetine. See NICE's information on prescribing medicines.\n\nIn the event that an adult with OCD or BDD develops marked and/or prolonged akathisia, restlessness or agitation while taking an SSRI, the use of the drug should be reviewed. If the patient prefers, the drug should be changed to a different SSRI.\n\nHealthcare professionals should be aware of the increased risk of drug interactions when prescribing an SSRI to adults with OCD or BDD who are taking other medications.\n\nFor adults with OCD or BDD, if there has been no response to a full course of treatment with an SSRI, healthcare professionals should check that the patient has taken the drug regularly and in the prescribed dose and that there is no interference from alcohol or substance use.\n\nFor adults with OCD or BDD, if there has not been an adequate response to a standard dose of an SSRI, and there are no significant side effects after 4\xa0to 6\xa0weeks, a gradual increase in dose should be considered in line with the schedule suggested by the summary of product characteristics.\n\nFor adults with OCD or BDD, the rate at which the dose of an SSRI should be increased should take into account therapeutic response, adverse effects and patient preference. Patients should be warned about, and monitored for, the emergence of side effects during dose increases.\n\nIf treatment for OCD or BDD with an SSRI is effective, it should be continued for at least 12\xa0months to prevent relapse and allow for further improvements.\n\nWhen an adult with OCD or BDD has taken an SSRI for 12\xa0months after remission (symptoms are not clinically significant and the person is fully functioning for at least 12\xa0weeks), healthcare professionals should review with the patient the need for continued treatment. This review should consider the severity and duration of the initial illness, the number of previous episodes, the presence of residual symptoms, and concurrent psychosocial difficulties.\n\nIf treatment for OCD or BDD with an SSRI is continued for an extended period beyond 12\xa0months after remission (symptoms are not clinically significant and the person is fully functioning for at least 12\xa0weeks), the need for continuation should be reviewed at regular intervals, agreed between the patient and the prescriber, and written in the notes.\n\nFor adults with OCD or BDD, to minimise discontinuation or withdrawal symptoms when reducing or stopping SSRIs, the dose should be tapered gradually over several weeks according to the person's need. The rate of reduction should take into account the starting dose, the drug half‑life and particular profiles of adverse effects.\n\nHealthcare professionals should encourage adults with OCD or BDD who are discontinuing SSRI treatment to seek advice if they experience significant discontinuation or withdrawal symptoms.\n\nThe following drugs should not normally be used to treat OCD or BDD without comorbidity:\n\ntricyclic antidepressants other than clomipramine\n\ntricyclic‑related antidepressants\n\nserotonin and noradrenaline reuptake inhibitors (SNRIs), including venlafaxine\n\nmonoamine oxidase inhibitors (MAOIs)\n\nanxiolytics (except cautiously for short periods to counter the early activation of SSRIs).\n\nAntipsychotics as a monotherapy should not normally be used for treating OCD.\n\nAntipsychotics as a monotherapy should not normally be used for treating BDD (including beliefs of delusional intensity).\n\n## Poor response to initial treatment in adults\n\nIf initial treatment does not result in a clinically significant improvement in both symptoms and functioning, other treatment options should be considered. When additional treatment options also fail to produce an adequate response, multidisciplinary teams with specific expertise in OCD/BDD should become involved. Their role should include supporting and collaborating with those professionals already involved in an individual's care.\n\nFor guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.\n\nFor adults with OCD or BDD, if there has not been an adequate response to treatment with an SSRI alone (within 12\xa0weeks) or CBT (including ERP) alone (more than 10\xa0therapist hours per patient), a multidisciplinary review should be carried out.\n\nFollowing multidisciplinary review, for adults with OCD or BDD, if there has not been an adequate response to treatment with an SSRI alone (within 12\xa0weeks) or CBT (including ERP) alone (more than 10\xa0therapist hours per patient), combined treatment with CBT (including ERP) and an SSRI should be offered.\n\nFor adults with OCD or BDD, if there has not been an adequate response after 12\xa0weeks of combined treatment with CBT (including ERP) and an SSRI, or there has been no response to an SSRI alone, or the patient has not engaged with CBT, a different SSRI or clomipramine should be offered.\n\nClomipramine should be considered in the treatment of adults with OCD or BDD after an adequate trial of at least 1\xa0SSRI has been ineffective or poorly tolerated, if the patient prefers clomipramine or has had a previous good response to it.\n\nFor adults with OCD or BDD, if there has been no response to a full trial of at least 1\xa0SSRI alone, a full trial of combined treatment with CBT (including ERP) and an SSRI, and a full trial of clomipramine alone, the patient should be referred to a multidisciplinary team with specific expertise in the treatment of OCD/BDD for assessment and further treatment planning.\n\nThe assessment of adults with OCD or BDD referred to multidisciplinary teams with specific expertise in OCD/BDD should include a comprehensive assessment of their symptom profile, previous pharmacological and psychological treatment history, adherence to prescribed medication, history of side effects, comorbid conditions such as depression, suicide risk, psychosocial stressors, relationship with family and/or carers and personality factors.\n\nFollowing multidisciplinary review, for adults with OCD if there has been no response to a full trial of at least 1\xa0SSRI alone, a full trial of combined treatment with CBT (including ERP) and an SSRI, and a full trial of clomipramine alone, the following treatment options should also be considered (note, there is no evidence of the optimal sequence of the options listed below):\n\nadditional CBT (including ERP) or cognitive therapy\n\nadding an antipsychotic to an SSRI or clomipramine\n\ncombining clomipramine and citalopram. Note that this is an off-label use of citalopram. See NICE's information on prescribing medicines.\n\nFollowing multidisciplinary review, for adults with BDD, if there has been no response to a full trial of at least 1\xa0SSRI alone, a full trial of combined treatment with CBT (including ERP) and an SSRI, and a full trial of clomipramine alone, the following treatment options should also be considered (note, there is no evidence of the optimal sequence of the options listed below):\n\nadditional CBT or cognitive therapy by a different multidisciplinary team with expertise in BDD\n\nadding buspirone to an SSRI.Note that this is an off-label use of buspirone. See NICE's information on prescribing medicines.\n\nFor adults with BDD, if there has been no response to treatment, or the patient is not receiving appropriate treatment, more intensive monitoring is needed because the risk of suicide is high in people with BDD.\n\nTreatments such as combined antidepressants and antipsychotic augmentation should not be routinely initiated in primary care.\n\nFor guidance on safe prescribing and managing withdrawal of antidepressants in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.\n\nFor adults with OCD or BDD who are at a significant risk of suicide, healthcare professionals should only prescribe small amounts of clomipramine at a time because of its toxicity in overdose (see the summary of product characteristics for details of dosage). The patient should be monitored regularly until the risk of suicide has subsided.\n\nAn electrocardiogram (ECG) should be carried out and a blood pressure measurement taken before prescribing clomipramine for adults with OCD or BDD at significant risk of cardiovascular disease.\n\nFor adults with OCD or BDD, if there has not been an adequate response to the standard dose of clomipramine, and there are no significant side effects, a gradual increase in dose should be considered in line with the schedule suggested by the summary of product characteristics.\n\nFor adults with OCD or BDD, treatment with clomipramine should be continued for at least 12\xa0months if it appears to be effective and because there may be further improvement.\n\nFor adults with OCD or BDD, when discontinuing clomipramine, doses should be reduced gradually in order to minimise potential discontinuation or withdrawal symptoms.\n\n## Poor response to initial treatment in children and young people\n\nCurrent published evidence suggests that SSRIs are effective in treating children and young people with OCD. The only SSRIs licensed for use in children and young people with OCD are fluvoxamine and sertraline. When used as a treatment for depression, SSRIs can cause significant adverse reactions, including increased suicidal thoughts and risk of self‑harm, but it is not known whether this same risk occurs with their use in OCD. SSRIs may be safer in depression when combined with psychological treatments (see NICE's guideline on depression in children and young people). Given that the UK regulatory authority has advised that similar adverse reactions cannot be ruled out in OCD, appropriate caution should be observed, especially in the presence of comorbid depression.\n\nFor a child or young person with OCD or BDD, if there has not been an adequate response within 12\xa0weeks to a full trial of CBT (including ERP) involving the family or carers, a multidisciplinary review should be carried out.\n\nFollowing multidisciplinary review, for a child (aged 8\xa0to 11\xa0years) with OCD or BDD with moderate to severe functional impairment, if there has not been an adequate response to CBT (including ERP) involving the family or carers, the addition of an SSRI to ongoing psychological treatment may be considered. Careful monitoring should be undertaken, particularly at the beginning of treatment.\n\nFollowing multidisciplinary review, for a young person (aged 12\xa0to 18\xa0years) with OCD or BDD with moderate to severe functional impairment, if there has not been an adequate response to CBT (including ERP) involving the family or carers, the addition of an SSRI to ongoing psychological treatment should be offered. Careful monitoring should be undertaken, particularly at the beginning of treatment.\n\nFor a child or a young person with OCD or BDD, if treatment with an SSRI in combination with CBT (including ERP) involving the family or carers is unsuccessful or is not tolerated because of side effects, the use of another SSRI or clomipramine with careful monitoring may be considered, especially if the child or young person has had a positive response to these alternatives in the past. This should also be in combination with CBT (including ERP). Note that this is an off-label use of clomipramine. See NICE's information on prescribing medicines.\n\n## How to use pharmacological treatments in children and young people\n\nIn adults with OCD treated by medication, there is some clinical trial evidence regarding the onset of therapeutic response, the dose needed, the rate of increase of dose, the duration of treatment and the likelihood of relapse on discontinuation. Trials of these aspects have not been done in children and/or young people, but the following good practice for prescribing SSRIs or clomipramine is based on adult trials and clinical experience.\n\nHow to use SSRIs in children and young people\n\nAn SSRI should only be prescribed to children and young people with OCD or BDD following assessment and diagnosis by a child and adolescent psychiatrist who should also be involved in decisions about dose changes and discontinuation.\n\nWhen an SSRI is prescribed to children and young people with OCD or BDD, it should be in combination with concurrent CBT (including ERP). If children and young people are unable to engage with concurrent CBT, specific arrangements should be made for careful monitoring of adverse events and these arrangements should be recorded in the notes.\n\nChildren and young people with OCD or BDD starting treatment with SSRIs should be carefully and frequently monitored and seen on an appropriate and regular basis. This should be agreed by the patient, his or her family or carers and the healthcare professional, and recorded in the notes.\n\nA licensed medication (sertraline or fluvoxamine) should be used when an SSRI is prescribed to children and young people with OCD, except in patients with significant comorbid depression when fluoxetine should be used, because of current regulatory requirements. Note the uses of sertraline for under\xa06s, fluvoxamine for under\xa08s, and fluoxetine for children and young people are off-label. See NICE's information on prescribing medicines.\n\nFluoxetine should be used when an SSRI is prescribed to children and young people with BDD. Note that this is an off-label use. See NICE's information on prescribing medicines.\n\nFor children and young people with OCD or BDD who also have significant depression, the NICE recommendations for the treatment of childhood depression should be followed and there should be specific monitoring for suicidal thoughts or behaviours. See NICE's guideline on depression in children and young people.\n\nChildren and young people with OCD or BDD starting treatment with SSRIs should be informed about the rationale for the drug treatment, the delay in onset of therapeutic response (up to 12\xa0weeks), the time course of treatment, the possible side effects and the need to take the medication as prescribed. Discussion of these issues should be supplemented by written information appropriate to the needs of the child or young person and their family or carers.\n\nThe starting dose of medication for children and young people with OCD or BDD should be low, especially in younger children. A half or quarter of the normal starting dose may be considered for the first week.\n\nIf a lower dose of medication for children and young people with OCD or BDD is ineffective, the dose should be increased until a therapeutic response is obtained, with careful and close monitoring for adverse events. The rate of increase should be gradual and should take into account the delay in therapeutic response (up to 12\xa0weeks) and the age of the patient. Maximum recommended doses for children and young people should not be exceeded.\n\nChildren and young people prescribed an SSRI, and their families or carers, should be informed by the prescribing doctor about the possible appearance of suicidal behaviour, self‑harm or hostility, particularly at the beginning of treatment. They should be advised that if there is any sign of new symptoms of these kinds, they should make urgent contact with their medical practitioner.\n\nWhere children or young people with OCD or BDD respond to treatment with an SSRI, medication should be continued for at least 6\xa0months post‑remission (that is, symptoms are not clinically significant and the child or young person is fully functioning for at least 12\xa0weeks).\n\nChildren and young people with OCD or BDD and their families or carers should be advised about the possible side effects of clomipramine, including toxicity in overdose.\n\nBefore starting treatment with clomipramine in children and young people with OCD or BDD, an ECG should be carried out to exclude cardiac conduction abnormalities.\n\nFor a child or young person with OCD or BDD, if there has not been an adequate response to the standard dose of clomipramine, and there are no significant side effects, a gradual increase in dose may be cautiously considered.\n\nTreatment of a child or young person with OCD or BDD with clomipramine should be continued for at least 6\xa0months if the treatment appears to be effective, because there may be further improvement in symptoms.\n\nIn children and young people with OCD or BDD, an attempt should be made to withdraw medication if remission has been achieved (that is, symptoms are no longer clinically significant and the child or young person is fully functioning) and maintained for at least 6\xa0months, and if that is their wish. Patients and their family or carers should be warned that relapse and/or discontinuation or withdrawal symptoms may occur. They should be advised to contact their medical practitioner should symptoms of discontinuation or withdrawal arise.\n\nFor children and young people with OCD or BDD, to minimise discontinuation or withdrawal symptoms on reducing or stopping antidepressants, particularly SSRIs, the dose should be tapered gradually over several weeks according to the individual's need. The rate of reduction should take into account the starting dose, the drug half‑life and particular profiles of adverse effects.\n\nChildren and young people with OCD or BDD should continue with psychological treatment throughout the period of drug discontinuation because this may reduce the risk of relapse.\n\nTricyclic antidepressants other than clomipramine should not be used to treat OCD or BDD in children and young people.\n\nOther antidepressants (MAOIs, SNRIs) should not be used to treat OCD or BDD in children and young people.\n\nAntipsychotics should not be used alone in the routine treatment of OCD or BDD in children or young people, but may be considered as an augmentation strategy.\n\n# Step 6: intensive treatment and inpatient services for people with OCD or BDD\n\nPeople with severe, chronic, treatment‑refractory OCD or BDD should have continuing access to specialist treatment services staffed by multidisciplinary teams of healthcare professionals with expertise in the management of the disorders.\n\nInpatient services, with specific expertise in OCD and BDD, are appropriate for a small proportion of people with these disorders, and may be considered when:\n\nthere is risk to life\n\nthere is severe self‑neglect\n\nthere is extreme distress or functional impairment\n\nthere has been no response to adequate trials of pharmacological, psychological or combined treatments over long periods of time in other settings\n\na person has additional diagnoses, such as severe depression, anorexia nervosa or schizophrenia, that make outpatient treatment more complex\n\na person has a reversal of normal night or day patterns that make attendance at any daytime therapy impossible\n\nthe compulsions and avoidance behaviour are so severe or habitual that they cannot undertake normal activities of daily living.\n\nA small minority of adults with long‑standing and disabling obsessive‑compulsive symptoms that interfere with daily living and have prevented them from developing a normal level of autonomy may, in addition to treatment, need suitable accommodation in a supportive environment that will enable them to develop life skills for independent living.\n\nNeurosurgery is not recommended in the treatment of OCD. However, if a patient requests neurosurgery because they have severe OCD that is refractory to other forms of treatment, the following should be taken into consideration.\n\nExisting published criteria (such as Matthews and Eljamel's Status of neurosurgery for mental disorder in Scotland) should be used to guide decisions about suitability.\n\nMultidisciplinary teams with a high degree of expertise in the pharmacological and psychological treatment of OCD should have been recently involved in the patient's care. All pharmacological options should have been considered and every attempt should have been made to engage the individual in CBT (including ERP) and cognitive therapy, including very intensive and/or inpatient treatments.\n\nStandardised assessment protocols should be used pre‑ and post‑operation and at medium‑ and long‑term follow‑ups in order to audit the interventions. These assessment protocols should include standardised measures of symptoms, quality of life, social and personality function, as well as comprehensive neuropsychological tests.\n\nServices offering assessment for neurosurgical treatments should have access to independent advice on issues such as adequacy of previous treatment and consent and should be subject to appropriate oversight.\n\nPost‑operative care should be carefully considered, including pharmacological and psychological therapies.\n\nServices offering assessment for neurosurgical treatments should be committed to sharing and publishing audit information.\n\nFor children and young people with severe OCD or BDD with high levels of distress and/or functional impairment, if there has been no response to adequate treatment in outpatient settings, or there is significant self‑neglect or risk of suicide, assessment for intensive inpatient treatment in units where specialist treatment for children or young people with OCD or BDD is available should be offered.\n\n# Discharge after recovery\n\nWhen a person of any age with OCD or BDD is in remission (symptoms are not clinically significant and the person is fully functioning for 12\xa0weeks), he or she should be reviewed regularly for 12\xa0months by a mental health professional. The exact frequency of contact should be agreed between the professional and the person with OCD or BDD and/or the family and/or carer and recorded in the notes. At the end of the 12‑month period if recovery is maintained the person can be discharged to primary care.\n\nOCD and BDD can have a fluctuating or episodic course, or relapse may occur after successful treatment. Therefore, people who have been successfully treated and discharged should be seen as soon as possible if re‑referred with further occurrences of OCD or BDD, rather than placed on a routine waiting list. For those in whom there has been no response to treatment, care coordination (or other suitable processes) should be used at the end of any specific treatment programme to identify any need for continuing support and appropriate services to address it.", 'Recommendations for research': "The Guideline Development Group has made the following recommendations for research, on the basis of its review of the evidence. The Group regards these recommendations as the most important research areas to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of recommendations for research is detailed in the full guideline.\n\n# Treatment of OCD and BDD among young people and young adults\n\nAppropriately blinded randomised controlled trials (RCTs) should be conducted to assess the acute and long‑term efficacy (including measures of social function and quality of life), acceptability and the cost effectiveness of cognitive behavioural therapy (CBT) and selective serotonin re uptake inhibitors (SSRIs), alone and in combination, compared with each other and with appropriate control treatments for both the psychological and pharmacological arms. These should be carried out in a broadly based sample of young people and young adults (for example, aged 12 to 25\xa0years) diagnosed with obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) across a range of functional impairment (using minimal exclusion criteria). The trials should be powered to examine the effect of treatment for combined versus single‑strand treatments and involve a follow‑up of 1, 2 and 5\xa0years. Any treatment received in the follow‑up period should also be recorded.\n\n# CBT treatment intensity formats among adults with OCD\n\nAppropriately blinded RCTs should be conducted to assess the efficacy (including measures of social function and quality of life), acceptability and the cost effectiveness of different delivery formats of CBT that include exposure and response prevention (ERP) for adults with OCD, including brief individual CBT using structured self‑help materials, brief individual CBT by telephone, group CBT and standard individual CBT compared with each other and with credible psychological treatment that is not specific to OCD and BDD (such as anxiety management training) in a broadly based sample of people diagnosed with OCD across a range of functional impairment (using minimal exclusion criteria). The trials should be powered to examine the effect of treatment in different bands of severity or functional impairment and involve a follow‑up of 1 and 2\xa0years. Any treatment received in the follow‑up period should also be recorded.\n\n# CBT for adults with OCD who have not responded to treatment\n\nAn appropriately blinded RCT should be conducted to assess the efficacy (including measures of social functioning and quality of life as well as OCD) of intensive versus spaced individual treatments (that include both ERP and cognitive therapy elements) compared with a treatment‑as‑usual control in a broadly based sample of adults diagnosed with OCD who have not responded to 1\xa0or more adequate trials of an SSRI or clomipramine and 1\xa0or more trials of CBT (that included ERP). The trial should be powered to examine the relative efficacy of intensive versus spaced treatment and involve a follow‑up of 1\xa0and 2\xa0years. Any treatment received in the follow‑up period should also be recorded.\n\n# Screening for OCD and BDD\n\nAppropriately designed studies should be conducted to compare validated screening instruments for the detection of OCD and BDD in children, young people and adults. An emphasis should be placed on examining those that use computer technology and more age‑appropriate methods of assessing both symptoms and functioning, taking into account cultural and ethnic variations in communication, and family values. For BDD, specific populations would include young people or adults who consult in dermatology or plastic surgery and those with other psychiatric disorders.\n\n# CBT for children and young people with OCD and BDD\n\nAn appropriately blinded RCT should be conducted to assess the efficacy (including measures of social functioning and quality of life) and the cost effectiveness of individual CBT and CBT involving the family or carers compared with each other and with a credible psychological treatment that is not specific to OCD and BDD (such as anxiety management training) in a broadly based sample of children and young people diagnosed with OCD and BDD (using minimal exclusion criteria). The trial should be powered to examine the effect of treatment in children and young people separately and involve a follow‑up of at least 1\xa0year.", 'Appendix A: Grading scheme': 'All evidence was classified according to an accepted hierarchy of evidence that was originally adapted from the US Agency for Healthcare Policy and Research Classification (see table 1). Recommendations were then graded A to C based on the level of associated evidence. This grading scheme is based on a scheme formulated by the Clinical Outcomes Group of the NHS Executive (1996).\n\nLevel\n\nType of evidence\n\nGrade\n\nEvidence\n\n\n\nEvidence obtained from a single randomised controlled trial or a meta‑analysis of randomised controlled trials\n\nA\n\nAt least 1\xa0randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation (evidence level\xa01) without extrapolation\n\na\n\nEvidence obtained from at least 1\xa0well‑designed controlled study without randomisation\n\nB\n\nWell‑conducted clinical studies but no randomised clinical trials on the topic of recommendation (evidence levels 2 or 3); or extrapolated from level 1 evidence\n\nb\n\nEvidence obtained from at least 1\xa0other well‑designed quasi-experimental study\n\n–\n\n–\n\n\n\nEvidence obtained from well‑designed non‑experimental descriptive studies, such as comparative studies, correlation studies and case studies\n\n–\n\n–\n\n\n\nEvidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities\n\nC\n\nExpert committee reports or opinions and/or clinical experiences of respected authorities (evidence level 4) or extrapolated from level 1 or 2 evidence. This grading indicates that directly applicable clinical studies of good quality are absent or not readily available\n\n\n\nEvidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities\n\nGPP\n\nRecommended good practice based on the clinical experience of the GDG.\n\nAdapted from Eccles M, Mason J (2001) How to develop cost‑conscious guidelines. Health Technology Assessment 5:16 and Mann T (1996) Clinical Guidelines: Using Clinical Guidelines to Improve Patient Care Within the NHS. London: Department of Health.', 'Appendix D: Technical detail on the criteria for audit': "# Possible objectives for an audit\n\nOne or more audits could be carried out in different care settings to ensure that:\n\nindividuals with obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) are involved in their care\n\ntreatment options are appropriately offered and provided for individuals with OCD or BDD.\n\n# People that could be included in an audit and time period for selection\n\nA single audit could include all individuals with OCD or BDD. Alternatively, individual audits could be undertaken on specific groups of individuals such as:\n\npeople with OCD or BDD at a particular stage (for example, to study assessment)\n\na sample of people with OCD or BDD from particular populations in primary care.\n\n# Measures that could be used as a basis for an audit\n\nPlease see tables below.\n\nCriterion\n\nException\n\nDefinition of terms\n\nEach primary care trust, mental healthcare trust, and children's trust that provides mental health services has access to a specialist multidisciplinary obsessive-compulsive disorder (OCD)/body dysmorphic disorder (BDD) team.\n\na) Operational policies in each primary care trust, mental healthcare trust and children's trust that provides mental health services specify procedure for accessing specialist OCD/BDD team\n\nb) Specialist teams offer a liaison function to other mental health professionals\n\nNone\n\nA specialist OCD/BDD team is able to conduct expert assessment, specialist cognitive‑behavioural and pharmacological treatment and provide age‑appropriate care\n\nA liaison function will aim to: increase skills in the assessment and evidence‑based treatment of people with OCD or BDD; provide high‑quality advice; aid understanding of the needs of family or carers and developmental needs\n\nCriterion\n\nException\n\nDefinition of terms\n\nPeople with obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) who have relapsed following successful treatment are seen by a healthcare professional as soon as possible if re‑referred, and where there has been no response to treatment are appropriately supported.\n\na) Operational policies indicate the re‑referral pathway\n\nb) Operational policies indicate that care coordination or other suitable process is followed for people where there has been no response to treatment\n\nPerson with OCD or BDD refuses re‑referral\n\n\n\nNone\n\nCriterion\n\nException\n\nDefinition of terms\n\nIn their initial treatment, adults who have mild obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD), or those who express a preference, are offered a low intensity psychological treatment.\n\na) Clinical notes indicate that people are informed of low intensity treatment options\n\nb) Clinical notes indicate the clinical outcome of low intensity interventions\n\n\n\nAdults with moderate to severe OCD or BDD\n\nChildren and young people\n\nAdults who refuse this treatment\n\nLow intensity treatments (less than 10 therapist hours) include:\n\nbrief individual cognitive behavioural therapy (CBT; including ERP [exposure and response prevention]) using structured self‑help materials\n\nbrief individual CBT (including ERP) by telephone\n\ngroup CBT (including ERP) – note the patient may be receiving more than 10\xa0hours of therapy in this format\n\nCriterion\n\nException\n\nDefinition of terms\n\nWhere adults have been unable to engage with low intensity treatment, or there has been no response to low intensity treatment, adults with mild obsessive-compulsive disorder (OCD) are offered more intensive treatment interventions.\n\na) Clinical notes indicate that people have been informed of the possibility of intensive cognitive behavioural therapy (CBT; including ERP [exposure and response prevention]) or a selective serotonin reuptake inhibitor (SSRI)\n\nb) Clinical notes indicate the clinical outcome of the intervention offered\n\nAdults where there is improvement with low intensity interventions\n\nChildren and young people\n\nAdults who refuse these treatments\n\nMore intensive treatment interventions include: a choice of either a course of an SSRI, or more intensive CBT (including ERP; of more than 10\xa0therapist hours per patient)\n\nCriterion\n\nException\n\nDefinition of terms\n\nAdults who have obsessive-compulsive disorder (OCD) with moderate functional impairment are offered the choice of either a course of a selective serotonin reuptake inhibitor (SSRI) or more intensive cognitive behavioural therapy (CBT; including ERP [exposure and response prevention]).\n\na) Clinical notes indicate that people have been informed of the possibility of more intensive CBT (including ERP) or an SSRI\n\nb) Clinical notes indicate the clinical outcome of the intervention offered\n\nChildren and young people\n\n\n\nMore intensive CBT (including ERP) means: more than 10\xa0therapist hours per patient\n\nCriterion\n\nException\n\nDefinition of terms\n\nAdults who have moderate body dysmorphic disorder (BDD) are offered the choice of a selective serotonin reuptake inhibitor (SSRI) or more intensive individual cognitive behavioural therapy (CBT; including ERP) or an SSRI.\n\na) Clinical notes indicate that people have been informed of the possibility of intensive individual CBT (including ERP [exposure and response prevention]) or an SSRI\n\nb) Clinical notes indicate the clinical outcome of the intervention offered\n\nChildren and young people\n\n\n\nCBT (including ERP) means: ERP that addresses key features of BDD.\n\nCriterion\n\nException\n\nDefinition of terms\n\nChildren and young people who have obsessive-compulsive disorder (OCD) with moderate or severe impairment or those with mild impairment where there is no response to guided self‑help, or where guided self‑help has been refused, will be offered cognitive behavioural therapy (CBT; including ERP [exposure and response prevention]) as the treatment of choice.\n\na) Clinical notes indicate that the child or young person and the family or carer were informed of possibility of CBT\n\nb) Clinical notes identify the clinical outcome of CBT\n\nChildren and young people who refuse CBT (including ERP)\n\nCBT (including ERP) means: treatment involving the family or carers and adapted to suit the developmental age of the child. Group or individual formats should be offered depending upon the preference of the child or young person and their family or carers\n\nCriterion\n\nException\n\nDefinition of terms\n\nChildren who have obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) where there has not been an adequate response to cognitive behavioural therapy (CBT; including ERP [exposure and response prevention]) attend a multidisciplinary review (with family or carers) where the use of a selective serotonin reuptake inhibitor (SSRI) is considered in addition to ongoing psychological treatment.\n\na) Clinical notes indicate a multidisciplinary review occurred and identified that the use of an SSRI in addition to ongoing psychological treatment was explored in detail\n\nb) Clinical notes indicate that careful monitoring was carried out\n\nc) Clinical notes indicate the clinical outcome of the intervention offered\n\nChildren who respond to CBT (including ERP)\n\n\n\nChildren: aged 8 to 11\xa0years\n\nCareful monitoring: being seen frequently on an appropriate and regular basis agreed by the patient, his or her family or carers and the healthcare professional, and recorded in the notes\n\nCriterion\n\nException\n\nDefinition of terms\n\nYoung people who have obsessive-compulsive disorder (OCD) or body dysmorphic disorder (BDD) where there has not been an adequate response to cognitive behavioural therapy (CBT; including ERP [exposure and response prevention]) attend a multidisciplinary review (with family or carers) where the use of a selective serotonin reuptake inhibitor (SSRI) is considered in addition to ongoing psychological treatment\n\na) Clinical notes indicate a multidisciplinary review occurred and identified that the use of an SSRI in addition to ongoing psychological treatment was explored in detail\n\nb) Clinical notes indicate that careful monitoring was carried out\n\nc) Clinical notes indicate the clinical outcome of the intervention offered\n\nYoung people who respond to CBT (including ERP)\n\n\n\nYoung people: aged 12 to 18\xa0years\n\nCareful monitoring: being seen frequently on an appropriate and regular basis agreed by the patient, his or her family or carers and the healthcare professional, and recorded in the notes\n\nCriterion\n\nException\n\nDefinition of terms\n\nChildren and young people with body dysmorphic disorder (BDD) are considered for cognitive behavioural therapy (CBT; including ERP [exposure and response prevention]) as first‑line treatment.\n\na) Clinical notes indicate that the healthcare professional responsible has discussed the need for CBT (including ERP) and an arrangement has been made\n\nb) Clinical notes indicate the clinical outcome of the intervention offered\n\nChildren or young people who refuse treatment\n\n\n\nChildren: aged 8 to 11\xa0years.\n\nYoung people: aged 12 to 18\xa0years.\n\nCBT (including ERP) means: involving the family or carers and adapted to the developmental age of the child or young person"}	https://www.nice.org.uk/guidance/cg31	This guideline covers recognising, assessing, diagnosing and treating obsessive-compulsive disorder and body dysmorphic disorder in adults, young people and children (aged 8 years and older). It aims to improve the diagnosis and treatment of obsessive-compulsive disorder and body dysmorphic disorder. It includes recommendations on how families and carers may be able to support people with either of these conditions, and how they can get support for themselves.
763a1b4bb7eecc0801d8c67217096fe3a882eef8	nice	Intramural urethral bulking procedures for stress urinary incontinence in women	Intramural urethral bulking procedures for stress urinary incontinence in women Evidence-based recommendations on intramural urethral bulking procedures for stress urinary incontinence in women. Intramural urethral bulking aims to augment the urethral wall and increase the urethral closure force. # Guidance Current evidence on the safety and short-term efficacy of intramural urethral bulking procedures for stress urinary incontinence is adequate to support the use of these procedures provided that normal arrangements are in place for clinical governance and for audit or research. Clinicians should ensure that patients understand that the benefits of the procedures diminish in the long term and provide them with clear written information. In addition, use of the Institute's information for the public is recommended. Further publication of longer-term efficacy outcomes will be useful. Clinicians should submit data to the British Association of Urological Surgeons registry, or the British Society of Urogynaecologists registry (for further information contact the British Society of Urogynaecologists).# The procedure # Indications Stress urinary incontinence is the involuntary leakage of urine during exercise or movements such as coughing, sneezing and laughing. It is usually caused by weak or damaged muscles and connective tissues of the pelvic floor, or by weakness of the urethral sphincter itself. It is estimated that 10–52% of adult women have some form of incontinence. Typically, first-line treatment is conservative and includes pelvic floor muscle training, electrical stimulation and biofeedback. If the condition does not improve, surgical alternatives in women may include colposuspension, tension-free vaginal tape, transobturator foramen procedures or traditional suburethral slings. # Outline of the procedure Intramural urethral bulking aims to augment the urethral wall and increase the urethral closure force. Several millilitres of bulking agent are injected into the submucosa of the proximal urethra just distal to the bladder neck. The injections are usually administered under local anaesthesia, either transurethrally or para-urethrally. Injections are undertaken either under vision using a cytoscope; or blindly, using a non-endoscopic implantation device. A number of bulking agents are currently available. # Efficacy A small randomised controlled trial reported that 53% (34/64) of patients treated by urethral bulking with collagen had no incontinence at 12 months, compared with 72% (39/54) treated with conventional open surgery. One case series of patients treated with collagen reported that, after 12 months, 42% (38/90) had either no incontinence or an improvement in symptoms, as measured objectively using cystometry and abdominal leak point pressure. One case series of patients treated with silicone particles reported that 68% (69/102) had either no incontinence or marked improvement after a mean follow-up of 3 months. This proportion decreased to 48% (40/84) after a mean follow-up of 18 months. Four randomised controlled trials reported no difference in efficacy between different bulking agents. For more details, refer to the Sources of evidence. The Specialist Advisors noted that efficacy may depend on patient selection, the bulking agent used and the injection technique. # Safety Five case series reported safety data on a total of 389 patients. The most commonly reported adverse events were urinary tract infection, affecting 1% (1/102) to 12% (11/90) of patients, and urinary retention, affecting 0% (0/40) to 11% (10/90) of patients. Other reported complications included abscess at the injection site, urgency of micturition and prolonged pain. For more details, refer to the Sources of evidence. The Specialist Advisors stated that migration of the bulking agent, voiding difficulties, urinary tract infection and allergic reaction are potential adverse events. Haemorrhage was listed as a rare potential adverse event. # Other comments The Committee noted that a variety of bulking agents may be used for these procedures which may have different risk and benefit profiles. The Committee particularly noted that the benefits of these procedures diminish with time but that the procedure can be repeated.# Further information NICE has issued guidance on tension-free vaginal tape (replaced by NICE clinical guideline 40, 'Urinary incontinence: the management of urinary incontinence in women'), transobturator foramen procedures for stress urinary incontinence and insertion of extra-urethral (non-circumferential) retropubic adjustable compression devices. NICE is also producing guidance on insertion of biological slings for stress urinary incontinence . Andrew DillonChief ExecutiveNovember 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of intramural urethral bulking procedures for stress urinary incontinence in women', August 2004. # Information for patients NICE has produced information describing its guidance on this procedure for patients, carers, and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and short-term efficacy of intramural urethral bulking procedures for stress urinary incontinence is adequate to support the use of these procedures provided that normal arrangements are in place for clinical governance and for audit or research.\n\nClinicians should ensure that patients understand that the benefits of the procedures diminish in the long term and provide them with clear written information. In addition, use of the Institute's information for the public is recommended.\n\nFurther publication of longer-term efficacy outcomes will be useful. Clinicians should submit data to the British Association of Urological Surgeons registry, or the British Society of Urogynaecologists registry (for further information contact the British Society of Urogynaecologists).", 'The procedure': '# Indications\n\nStress urinary incontinence is the involuntary leakage of urine during exercise or movements such as coughing, sneezing and laughing. It is usually caused by weak or damaged muscles and connective tissues of the pelvic floor, or by weakness of the urethral sphincter itself. It is estimated that 10–52% of adult women have some form of incontinence.\n\nTypically, first-line treatment is conservative and includes pelvic floor muscle training, electrical stimulation and biofeedback. If the condition does not improve, surgical alternatives in women may include colposuspension, tension-free vaginal tape, transobturator foramen procedures or traditional suburethral slings.\n\n# Outline of the procedure\n\nIntramural urethral bulking aims to augment the urethral wall and increase the urethral closure force. Several millilitres of bulking agent are injected into the submucosa of the proximal urethra just distal to the bladder neck. The injections are usually administered under local anaesthesia, either transurethrally or para-urethrally. Injections are undertaken either under vision using a cytoscope; or blindly, using a non-endoscopic implantation device.\n\nA number of bulking agents are currently available.\n\n# Efficacy\n\nA small randomised controlled trial reported that 53% (34/64) of patients treated by urethral bulking with collagen had no incontinence at 12 months, compared with 72% (39/54) treated with conventional open surgery.\n\nOne case series of patients treated with collagen reported that, after 12 months, 42% (38/90) had either no incontinence or an improvement in symptoms, as measured objectively using cystometry and abdominal leak point pressure. One case series of patients treated with silicone particles reported that 68% (69/102) had either no incontinence or marked improvement after a mean follow-up of 3 months. This proportion decreased to 48% (40/84) after a mean follow-up of 18 months. Four randomised controlled trials reported no difference in efficacy between different bulking agents. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that efficacy may depend on patient selection, the bulking agent used and the injection technique.\n\n# Safety\n\nFive case series reported safety data on a total of 389 patients. The most commonly reported adverse events were urinary tract infection, affecting 1% (1/102) to 12% (11/90) of patients, and urinary retention, affecting 0% (0/40) to 11% (10/90) of patients. Other reported complications included abscess at the injection site, urgency of micturition and prolonged pain. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that migration of the bulking agent, voiding difficulties, urinary tract infection and allergic reaction are potential adverse events. Haemorrhage was listed as a rare potential adverse event.\n\n# Other comments\n\nThe Committee noted that a variety of bulking agents may be used for these procedures which may have different risk and benefit profiles.\n\nThe Committee particularly noted that the benefits of these procedures diminish with time but that the procedure can be repeated.', 'Further information': "NICE has issued guidance on tension-free vaginal tape (replaced by NICE clinical guideline 40, 'Urinary incontinence: the management of urinary incontinence in women'), transobturator foramen procedures for stress urinary incontinence and insertion of extra-urethral (non-circumferential) retropubic adjustable compression devices. NICE is also producing guidance on insertion of biological slings for stress urinary incontinence [Now published as 'Insertion of biological slings for stress urinary incontinence'].\n\nAndrew DillonChief ExecutiveNovember 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of intramural urethral bulking procedures for stress urinary incontinence in women', August 2004.\n\n# Information for patients\n\nNICE has produced information describing its guidance on this procedure for patients, carers, and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg138	Evidence-based recommendations on intramural urethral bulking procedures for stress urinary incontinence in women. Intramural urethral bulking aims to augment the urethral wall and increase the urethral closure force.
dde414605cccd8f4ca0594113e26ce64501e125e	nice	Metatarsophalangeal joint replacement of the hallux	Metatarsophalangeal joint replacement of the hallux # Guidance Current evidence on the safety and efficacy of metatarsophalangeal joint replacement of the hallux appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Clinicians should ensure that patients fully understand the uncertainties about the place of this procedure in relation to alternative treatment options. Patients should be provided with clear written information and, in addition, use of the Institute's information for the public is recommended. Patient selection is important, and should take into consideration the likely intensity and duration of use of the joint based on the patient's activities and aspirations. Further research will be useful in establishing the long-term outcomes of different types of prosthesis.# The procedure # Indications Osteoarthritis and rheumatoid arthritis commonly affect the metatarsophalangeal (MTP) joint at the base of the big toe. The joint may become predominantly stiff (hallux rigidus) or deformed (hallux valgus). Conservative treatments include exercise, physiotherapy, analgesics, non-steroidal anti-inflammatory tablets or cream, and steroid injections into the joint. Surgery may be required in patients with severe symptoms that do not respond to conservative measures. The main surgical options are fusion of the joint (arthrodesis), simple excision of the joint (Keller's procedure) and joint replacement with an artificial implant. # Outline of the procedure MTP joint replacement is carried out under general or regional anaesthesia using tourniquet control. An incision is made over the joint and the capsule is exposed by dividing tissue and retracting tendon. The joint surfaces are excised and the medullary canals of the first metatarsal and proximal phalanx are reamed to accommodate the prosthetic joint implant. A preliminary reduction with a trial implant is done to ensure a snug fit and the implant components are then placed in each canal. The joint capsule is closed and a flexible splint is used postoperatively to maintain the correct position. # Efficacy The main outcome measures reported were pain relief and patient satisfaction. Three studies reported that 73% (8/11), 79% (46/58) and 100% (7/7) of joints with implants were pain free after mean follow-ups of 17 months, 12 years and 35 months, respectively. Another study including 86 implants reported a statistically significant improvement in pain scores after the procedure. Two further studies reported pain relief in 66% (59/90) of implants and 94% (30/32) of patients (mean follow-ups of 3 years and 8 years, respectively). Four studies reported that between 74% (29/39) and 88% (7/8) of patients were completely satisfied with the procedure (mean follow-ups of 12 months and 17 months, respectively). For more details, refer to the Sources of evidence. Most of the Specialist Advisors stated that this was an established technique. However, there is limited evidence on the durability of the newer implants. # Safety The main complication reported was the formation of osteophytes around the implant. This affected between 4% (2/49) and 71% (41/58) of implants. Fractures were seen radiologically in 0% (0/106) to 29% (21/73) of implants, and frequency of fracture was related to the length of time that the implant had been in place. At the follow-up assessment, between 0% (0/11) and 8% (3/37) of implants had needed to be removed (mean follow-ups of 17 and 70 months, respectively). Other complications included malpositioning of the implant, infection, inflammation, dislocation and persistent pain. For more details, refer to the Sources of evidence. The Specialist Advisors stated that potential adverse events included persistent pain, infection, implant loosening, implant fracture, osteolysis, bone over-production, cyst formation, silastic granulomas and transfer metatarsalgia. Some of these complications may necessitate removal of the joint. # Other comments Radiological follow-up may demonstrate fracture of protheses or immobility of joints in the long term. However, the influence of these changes on symptom relief remains unclear.# Further information The Medicines and Healthcare products Regulatory Agency (MHRA) has issued the following device alert notices: DA2002(03), Screw-Fit Ceramic Toe Joint (Metatarsophalangeal) Replacement Prosthesis; and MDA/2004/009, Moje Press-Fit Ceramic Toe Joint Prosthesis. Andrew DillonChief ExecutiveNovember 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedures overview of metatarsophalangeal joint replacement of the hallux', February 2005. # Information for the public NICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of metatarsophalangeal joint replacement of the hallux appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians should ensure that patients fully understand the uncertainties about the place of this procedure in relation to alternative treatment options. Patients should be provided with clear written information and, in addition, use of the Institute's information for the public is recommended.\n\nPatient selection is important, and should take into consideration the likely intensity and duration of use of the joint based on the patient's activities and aspirations.\n\nFurther research will be useful in establishing the long-term outcomes of different types of prosthesis.", 'The procedure': "# Indications\n\nOsteoarthritis and rheumatoid arthritis commonly affect the metatarsophalangeal (MTP) joint at the base of the big toe. The joint may become predominantly stiff (hallux rigidus) or deformed (hallux valgus).\n\nConservative treatments include exercise, physiotherapy, analgesics, non-steroidal anti-inflammatory tablets or cream, and steroid injections into the joint. Surgery may be required in patients with severe symptoms that do not respond to conservative measures. The main surgical options are fusion of the joint (arthrodesis), simple excision of the joint (Keller's procedure) and joint replacement with an artificial implant.\n\n# Outline of the procedure\n\nMTP joint replacement is carried out under general or regional anaesthesia using tourniquet control. An incision is made over the joint and the capsule is exposed by dividing tissue and retracting tendon. The joint surfaces are excised and the medullary canals of the first metatarsal and proximal phalanx are reamed to accommodate the prosthetic joint implant. A preliminary reduction with a trial implant is done to ensure a snug fit and the implant components are then placed in each canal. The joint capsule is closed and a flexible splint is used postoperatively to maintain the correct position.\n\n# Efficacy\n\nThe main outcome measures reported were pain relief and patient satisfaction. Three studies reported that 73% (8/11), 79% (46/58) and 100% (7/7) of joints with implants were pain free after mean follow-ups of 17 months, 12 years and 35 months, respectively. Another study including 86 implants reported a statistically significant improvement in pain scores after the procedure. Two further studies reported pain relief in 66% (59/90) of implants and 94% (30/32) of patients (mean follow-ups of 3 years and 8 years, respectively).\n\nFour studies reported that between 74% (29/39) and 88% (7/8) of patients were completely satisfied with the procedure (mean follow-ups of 12 months and 17 months, respectively). For more details, refer to the Sources of evidence.\n\nMost of the Specialist Advisors stated that this was an established technique. However, there is limited evidence on the durability of the newer implants.\n\n# Safety\n\nThe main complication reported was the formation of osteophytes around the implant. This affected between 4% (2/49) and 71% (41/58) of implants. Fractures were seen radiologically in 0% (0/106) to 29% (21/73) of implants, and frequency of fracture was related to the length of time that the implant had been in place. At the follow-up assessment, between 0% (0/11) and 8% (3/37) of implants had needed to be removed (mean follow-ups of 17 and 70 months, respectively). Other complications included malpositioning of the implant, infection, inflammation, dislocation and persistent pain. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that potential adverse events included persistent pain, infection, implant loosening, implant fracture, osteolysis, bone over-production, cyst formation, silastic granulomas and transfer metatarsalgia. Some of these complications may necessitate removal of the joint.\n\n# Other comments\n\nRadiological follow-up may demonstrate fracture of protheses or immobility of joints in the long term. However, the influence of these changes on symptom relief remains unclear.", 'Further information': "The Medicines and Healthcare products Regulatory Agency (MHRA) has issued the following device alert notices: DA2002(03), Screw-Fit Ceramic Toe Joint (Metatarsophalangeal) Replacement Prosthesis; and MDA/2004/009, Moje Press-Fit Ceramic Toe Joint Prosthesis.\n\nAndrew DillonChief ExecutiveNovember 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedures overview of metatarsophalangeal joint replacement of the hallux', February 2005.\n\n# Information for the public\n\nNICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg140
f9914e8589f39900552194b65c4f2d5a24cc4db0	nice	Automated percutaneous mechanical lumbar discectomy	Automated percutaneous mechanical lumbar discectomy # Guidance Current evidence suggests that there are no major safety concerns associated with automated percutaneous mechanical lumbar discectomy. There is limited evidence of efficacy based on uncontrolled case series of heterogeneous groups of patients, but evidence from small randomised controlled trials shows conflicting results. In view of the uncertainties about the efficacy of the procedure, it should not be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake automated percutaneous mechanical lumbar discectomy should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's efficacy and provide them with clear written information. In addition, use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having automated mechanical percutaneous lumbar discectomy. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Lumbar radicular pain, also known as sciatica, refers to pain that begins in the lower back and radiates down the leg. It is commonly caused by a herniated (or prolapsed) lumbar intervertebral disc. The herniation is a result of a protrusion of the nucleus pulposus through a tear in the surrounding annulus fibrosus. The annulus fibrosus may rupture completely, resulting in an extruded disc, or may remain intact but stretched, resulting in a contained disc prolapse. This may then compress one or more nerve roots, causing pain, numbness or weakness in the leg. Conservative treatments include the use of analgesics, non-steroidal anti-inflammatory medicines, physical therapy and hot or cold compresses. Epidural injections of corticosteroid may also be used. Surgery to remove disc material may be considered if there is nerve compression or persistent symptoms that are unresponsive to conservative treatment. Alternative surgical treatments include open discectomy and minimally invasive microdiscectomy. # Outline of the procedure Automated percutaneous mechanical lumbar discectomy is performed using local anaesthetic with or without conscious sedation. Under fluoroscopic guidance, a cannula is placed centrally within the disc using a posterolateral approach on the symptomatic side. A probe connected to an automated cutting and aspiration device is then introduced through the cannula. The disc is aspirated until no more nuclear material can be obtained. # Efficacy In a randomised controlled trial (RCT) of 71 patients, 29% (9/31) had a successful outcome after automated percutaneous lumbar discectomy, compared with 80% (32/40) of patients after microdiscectomy (p < 0.001). In a second RCT, 41% (7/17) of patients had an 'excellent' or 'good' outcome after automated percutaneous lumbar discectomy, compared with 40% (4/10) of patients after conventional discectomy. A third RCT compared automated percutaneous lumbar discectomy with chemonucleolysis and found that significantly more patients had a successful result after chemonucleolysis (61% versus 43% , p < 0.05). Two large case series reported that 68% (707/1047) and 82% (1216/1474) of patients had an 'excellent' or 'good' result at 6 months and 1 year, respectively. A third case series reported an overall success rate of 45% (52/115) after a mean follow-up of 55 months. In two further case series reports, 94% (47/50) and 52% (95/182) of patients were satisfied after mean follow-ups of 6 months and 2.5 years, respectively. For more details, refer to the Sources of evidence. The Specialist Advisors stated that there was some uncertainty about the efficacy of the procedure. # Safety Few complications were reported. Three studies reported discitis in between 0.2% (2/1146) and 1% (2/182) of patients. Two studies reported haematoma in 0.1% (1/1146) and 1.4% (1/69) of patients. Other complications included back muscle spasms, minor bleeding, minor radicular injury and vasovagal syncope. For more details, refer to the Sources of evidence. The Specialist Advisors stated that vascular and nerve damage, discitis and infection were potential adverse effects of the procedure.# Further information The Institute has also published guidance on laser lumbar discectomy. Andrew DillonChief ExecutiveNovember 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedures overview of automated percutaneous mechanical lumbar discectomy', February 2005. # Information for the public NICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# Changes since publication As part of the NICE's work programme, the current guidance was considered for review in July 2009 but did not meet the review criteria as set out in the IP process guide. This guidance therefore remains current. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence suggests that there are no major safety concerns associated with automated percutaneous mechanical lumbar discectomy. There is limited evidence of efficacy based on uncontrolled case series of heterogeneous groups of patients, but evidence from small randomised controlled trials shows conflicting results. In view of the uncertainties about the efficacy of the procedure, it should not be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake automated percutaneous mechanical lumbar discectomy should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's efficacy and provide them with clear written information. In addition, use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having automated mechanical percutaneous lumbar discectomy. The Institute may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nLumbar radicular pain, also known as sciatica, refers to pain that begins in the lower back and radiates down the leg. It is commonly caused by a herniated (or prolapsed) lumbar intervertebral disc. The herniation is a result of a protrusion of the nucleus pulposus through a tear in the surrounding annulus fibrosus. The annulus fibrosus may rupture completely, resulting in an extruded disc, or may remain intact but stretched, resulting in a contained disc prolapse. This may then compress one or more nerve roots, causing pain, numbness or weakness in the leg.\n\nConservative treatments include the use of analgesics, non-steroidal anti-inflammatory medicines, physical therapy and hot or cold compresses. Epidural injections of corticosteroid may also be used. Surgery to remove disc material may be considered if there is nerve compression or persistent symptoms that are unresponsive to conservative treatment.\n\nAlternative surgical treatments include open discectomy and minimally invasive microdiscectomy.\n\n# Outline of the procedure\n\nAutomated percutaneous mechanical lumbar discectomy is performed using local anaesthetic with or without conscious sedation. Under fluoroscopic guidance, a cannula is placed centrally within the disc using a posterolateral approach on the symptomatic side. A probe connected to an automated cutting and aspiration device is then introduced through the cannula. The disc is aspirated until no more nuclear material can be obtained.\n\n# Efficacy\n\nIn a randomised controlled trial (RCT) of 71 patients, 29% (9/31) had a successful outcome after automated percutaneous lumbar discectomy, compared with 80% (32/40) of patients after microdiscectomy (p < 0.001). In a second RCT, 41% (7/17) of patients had an 'excellent' or 'good' outcome after automated percutaneous lumbar discectomy, compared with 40% (4/10) of patients after conventional discectomy. A third RCT compared automated percutaneous lumbar discectomy with chemonucleolysis and found that significantly more patients had a successful result after chemonucleolysis (61% [44/72] versus 43% [30/69], p < 0.05).\n\nTwo large case series reported that 68% (707/1047) and 82% (1216/1474) of patients had an 'excellent' or 'good' result at 6 months and 1 year, respectively. A third case series reported an overall success rate of 45% (52/115) after a mean follow-up of 55 months. In two further case series reports, 94% (47/50) and 52% (95/182) of patients were satisfied after mean follow-ups of 6 months and 2.5 years, respectively. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that there was some uncertainty about the efficacy of the procedure.\n\n# Safety\n\nFew complications were reported. Three studies reported discitis in between 0.2% (2/1146) and 1% (2/182) of patients. Two studies reported haematoma in 0.1% (1/1146) and 1.4% (1/69) of patients. Other complications included back muscle spasms, minor bleeding, minor radicular injury and vasovagal syncope. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that vascular and nerve damage, discitis and infection were potential adverse effects of the procedure.", 'Further information': "The Institute has also published guidance on laser lumbar discectomy.\n\nAndrew DillonChief ExecutiveNovember 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedures overview of automated percutaneous mechanical lumbar discectomy', February 2005.\n\n# Information for the public\n\nNICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'Changes since publication': "As part of the NICE's work programme, the current guidance was considered for review in July 2009 but did not meet the review criteria as set out in the IP process guide. This guidance therefore remains current.\n\nJanuary 2012: minor maintenance.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg141
f4e52db5a7de677e0e3ed9a6e8100ef180a211e1	nice	Cryotherapy for malignant endobronchial obstruction	Cryotherapy for malignant endobronchial obstruction # Guidance Current evidence on the safety and efficacy of cryotherapy for malignant endobronchial obstruction appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Clinicians should ensure that patients fully understand that this is one of a variety of treatment options available. In addition, use of the Institute's information for the public is recommended.# The procedure # Indications Lung cancer is often at an advanced stage when it is diagnosed, with low survival rates. Patients can develop endobronchial lesions that obstruct the major airways, causing symptoms such as dyspnoea, cough, haemoptysis and postobstructive pneumonia. Bronchial obstruction may lead to gradual asphyxiation. The aim of treatment in patients with malignant endobronchial obstruction is mainly palliative. Current treatment options include a variety of endobronchial therapies such as bronchoscopic resection, brachytherapy, laser ablation, photodynamic therapy and stenting. Externalbeam radiotherapy and chemotherapy may also be used for palliative treatment. # Outline of the procedure General anaesthesia is usually used. A cryoprobe is inserted through a bronchoscope to reach the tumour; the probe diameter selected depends on the size and position of the tumour. After a period of freezing, the tumour is allowed to thaw until the probe separates from the tissue. The freeze/thaw cycle may be repeated two to three times in the same place. The probe is then moved to an adjacent area and the process is repeated until the whole tumour has been treated. Any resulting necrotic tumour material is then removed with forceps or using the cryoprobe. Further necrotic material may be expectorated during the following 24–48 hours. The procedure can be repeated if necessary. Cryotherapy does not provide immediate relief of bronchial obstruction and is therefore not suitable for the emergency treatment of acute respiratory distress. # Efficacy The main aim of the procedure in the studies was palliation of symptoms such as cough, dyspnoea and haemoptysis. In one case series of 521 patients, 86% (448/521) had improvement in one or more symptoms and quality of life scores were significantly improved. Dyspnoea improved in 59% (300/507) of patients. In two further studies, dyspnoea improved in 71% (12/17) and 81% (87/107) of patients. For more details, refer to the Sources of evidence. The Specialist Advisors did not express any major concerns about the efficacy of this procedure. # Safety A large case series study reported in-hospital mortality of 1% (7/521), which was due to respiratory failure. This study also reported that 3% (16/521) of patients developed respiratory distress after the procedure. A case series study of 27 patients reported one death due to myocardial ischaemia. Another study of 22 patients reported one cardiopulmonary arrest during the procedure. Two studies reported changes to the heart rhythm in 2% (12/521) and 11% (3/27) of patients. For more details, refer to the Sources of evidence. The Specialist Advisors listed haemorrhage, fistula formation, cardiac arrhythmias, respiratory distress and infection as potential adverse effects.# Further information The Institute has issued guidance on the diagnosis and treatment of lung cancer. The Institute has also issued Interventional Procedures guidance on the use of photodynamic therapy for advanced bronchial carcinoma and photodynamic therapy for localised inoperable endobronchial cancer. Andrew DillonChief ExecutiveNovember 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedures overview of cryotherapy for malignant endobronchial obstruction', February 2005. # Information for the public NICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of cryotherapy for malignant endobronchial obstruction appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians should ensure that patients fully understand that this is one of a variety of treatment options available. In addition, use of the Institute's information for the public is recommended.", 'The procedure': '# Indications\n\nLung cancer is often at an advanced stage when it is diagnosed, with low survival rates. Patients can develop endobronchial lesions that obstruct the major airways, causing symptoms such as dyspnoea, cough, haemoptysis and postobstructive pneumonia. Bronchial obstruction may lead to gradual asphyxiation.\n\nThe aim of treatment in patients with malignant endobronchial obstruction is mainly palliative. Current treatment options include a variety of endobronchial therapies such as bronchoscopic resection, brachytherapy, laser ablation, photodynamic therapy and stenting. Externalbeam radiotherapy and chemotherapy may also be used for palliative treatment.\n\n# Outline of the procedure\n\nGeneral anaesthesia is usually used. A cryoprobe is inserted through a bronchoscope to reach the tumour; the probe diameter selected depends on the size and position of the tumour. After a period of freezing, the tumour is allowed to thaw until the probe separates from the tissue. The freeze/thaw cycle may be repeated two to three times in the same place. The probe is then moved to an adjacent area and the process is repeated until the whole tumour has been treated. Any resulting necrotic tumour material is then removed with forceps or using the cryoprobe. Further necrotic material may be expectorated during the following 24–48 hours. The procedure can be repeated if necessary.\n\nCryotherapy does not provide immediate relief of bronchial obstruction and is therefore not suitable for the emergency treatment of acute respiratory distress.\n\n# Efficacy\n\nThe main aim of the procedure in the studies was palliation of symptoms such as cough, dyspnoea and haemoptysis. In one case series of 521 patients, 86% (448/521) had improvement in one or more symptoms and quality of life scores were significantly improved. Dyspnoea improved in 59% (300/507) of patients. In two further studies, dyspnoea improved in 71% (12/17) and 81% (87/107) of patients. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors did not express any major concerns about the efficacy of this procedure.\n\n# Safety\n\nA large case series study reported in-hospital mortality of 1% (7/521), which was due to respiratory failure. This study also reported that 3% (16/521) of patients developed respiratory distress after the procedure.\n\nA case series study of 27 patients reported one death due to myocardial ischaemia. Another study of 22 patients reported one cardiopulmonary arrest during the procedure. Two studies reported changes to the heart rhythm in 2% (12/521) and 11% (3/27) of patients. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors listed haemorrhage, fistula formation, cardiac arrhythmias, respiratory distress and infection as potential adverse effects.', 'Further information': "The Institute has issued guidance on the diagnosis and treatment of lung cancer. The Institute has also issued Interventional Procedures guidance on the use of photodynamic therapy for advanced bronchial carcinoma and photodynamic therapy for localised inoperable endobronchial cancer.\n\nAndrew DillonChief ExecutiveNovember 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedures overview of cryotherapy for malignant endobronchial obstruction', February 2005.\n\n# Information for the public\n\nNICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg142
36ab454d040d3edac13efc73ba335d2146f9b4ab	nice	Intraoperative blood cell salvage in obstetrics	Intraoperative blood cell salvage in obstetrics # Guidance Intraoperative blood cell salvage is an efficacious technique for blood replacement and its use is well established in other areas of medicine, but there are theoretical safety concerns when it is used in obstetric practice. Data collection is therefore important and clinicians should report all complications to the Medicines and Healthcare products Regulatory Agency. Whenever possible, patients should be fully informed of the potential complications. In addition, use of the Institute's information for the public is recommended. This procedure should only be performed by multidisciplinary teams who develop regular experience of intraoperative blood cell salvage.# The procedure # Indications Blood replacement may be required in obstetric practice during caesarean section, or after vaginal delivery in patients with conditions such as placenta previa or placenta accreta. The usual method of blood transfusion is standard (allogenic) transfusion from a donor. Intraoperative cell salvage may reduce the incidence of transfusion reactions and transfusion-related infection, compared with allogenic transfusion, and may also be useful when there are difficulties with cross-matching. Intraoperative blood cell salvage is commonly used in cardiac, orthopaedic and vascular surgery. It has not been routinely adopted in obstetrics because of specific concerns about amniotic fluid embolism and about haemolytic disease in future pregnancies as a result of re-infusing amniotic fluid or fetal red blood cells. # Outline of the procedure Intraoperative blood cell salvage is the process whereby blood shed during an operation is collected, filtered and washed to produce autologous red blood cells for transfusion to the patient. During intraoperative blood cell salvage in caesarean section, blood that is lost during the operation is aspirated from the surgical field using a catheter. The blood is then suctioned into a reservoir in which a filter removes gross debris. The filtered blood is washed and resuspended in saline for transfusion. It may be retransfused either during or after the operation. The aspirate may include amniotic fluid and blood cells from the fetus. A leukocyte depletion filter is nearly always used in this process to reduce the amount of amniotic fluid contaminants in transfused blood to levels approaching those found in maternal blood. # Efficacy In the blood cell salvage arm of a controlled trial, the median volume of re-infused blood was between 250 and 543 ml per woman (n = 139). There was no significant difference in length of hospital stay, or time on ventilatory support between women who received salvaged blood and women in the control group, who received standard transfusions. In another comparative study of 68 women who had had a caesarean section, the length of hospital stay was significantly shorter with the blood cell salvage procedure – 5.3 days compared with 7.3 days for women who had had the standard transfusion (p < 0.003). For more details, refer to the Sources of evidence. The Specialist Advisors noted that the efficacy of the procedure may depend on the rate and volume of the blood loss. # Safety In the blood cell salvage arm of a controlled trial, there were no instances of clinically apparent amniotic fluid embolism in 139 women. In the blood cell salvage arm of a comparative study of 68 women who had a caesarean section, there were no reported complications from re-infusing salvaged blood. Unused salvaged blood from 15 women was analysed and found to contain fetal haemoglobin at a concentration of 1.8–2.0% in 20% of cases (3/15). These same women were also found to have fetal haemoglobin in maternal blood samples. No complications were reported using salvaged blood treated with a leukocyte depletion filter in a series of four reported cases. For more details, refer to the Sources of evidence. In a controlled trial there was no significant difference in disseminated intravascular coagulation or rate of infection between women who received salvaged blood and women in the control group, who received standard transfusions. The Specialist Advisors noted that the theoretical safety concerns include infusion of fetal cells, which could potentially cause haemolytic disease in future pregnancies. Advisors also noted the potential risk of amniotic fluid embolism. Andrew DillonChief ExecutiveNovember 2005# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of intraoperative blood cell salvage in obstetric procedures', December 2004. # Information for the public NICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# Changes since publication NICE considered the evidence relating to the efficacy and safety of intraoperative blood cell salvage in obstetrics (IPG144) and for intraoperative red blood cell salvage during radical prostatectomy or radical cystectomy (NICE interventional procedure guidance 258) in response to concerns expressed about theoretical risks associated with the procedure. These concerns were the possibility of amniotic fluid embolism and haemolytic disease in future pregnancies when used in obstetrics, and reinfusion of malignant cells when used in radical prostatectomy/cystectomy. The evidence relating to safety of cell salvage in these procedures was considered adequate and therefore NICE does not intend to review its use in other specific clinical situations unless notified of new indications for intraoperative cell salvage in which there may be new safety concerns. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It has been incorporated into the NICE pathway on caesarean section, along with other related guidance and products. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Intraoperative blood cell salvage is an efficacious technique for blood replacement and its use is well established in other areas of medicine, but there are theoretical safety concerns when it is used in obstetric practice. Data collection is therefore important and clinicians should report all complications to the Medicines and Healthcare products Regulatory Agency.\n\nWhenever possible, patients should be fully informed of the potential complications. In addition, use of the Institute's information for the public is recommended.\n\nThis procedure should only be performed by multidisciplinary teams who develop regular experience of intraoperative blood cell salvage.", 'The procedure': '# Indications\n\nBlood replacement may be required in obstetric practice during caesarean section, or after vaginal delivery in patients with conditions such as placenta previa or placenta accreta. The usual method of blood transfusion is standard (allogenic) transfusion from a donor.\n\nIntraoperative cell salvage may reduce the incidence of transfusion reactions and transfusion-related infection, compared with allogenic transfusion, and may also be useful when there are difficulties with cross-matching.\n\nIntraoperative blood cell salvage is commonly used in cardiac, orthopaedic and vascular surgery. It has not been routinely adopted in obstetrics because of specific concerns about amniotic fluid embolism and about haemolytic disease in future pregnancies as a result of re-infusing amniotic fluid or fetal red blood cells.\n\n# Outline of the procedure\n\nIntraoperative blood cell salvage is the process whereby blood shed during an operation is collected, filtered and washed to produce autologous red blood cells for transfusion to the patient.\n\nDuring intraoperative blood cell salvage in caesarean section, blood that is lost during the operation is aspirated from the surgical field using a catheter. The blood is then suctioned into a reservoir in which a filter removes gross debris. The filtered blood is washed and resuspended in saline for transfusion. It may be retransfused either during or after the operation.\n\nThe aspirate may include amniotic fluid and blood cells from the fetus. A leukocyte depletion filter is nearly always used in this process to reduce the amount of amniotic fluid contaminants in transfused blood to levels approaching those found in maternal blood.\n\n# Efficacy\n\nIn the blood cell salvage arm of a controlled trial, the median volume of re-infused blood was between 250 and 543 ml per woman (n = 139). There was no significant difference in length of hospital stay, or time on ventilatory support between women who received salvaged blood and women in the control group, who received standard transfusions.\n\nIn another comparative study of 68 women who had had a caesarean section, the length of hospital stay was significantly shorter with the blood cell salvage procedure – 5.3 days compared with 7.3 days for women who had had the standard transfusion (p < 0.003). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that the efficacy of the procedure may depend on the rate and volume of the blood loss.\n\n# Safety\n\nIn the blood cell salvage arm of a controlled trial, there were no instances of clinically apparent amniotic fluid embolism in 139 women. In the blood cell salvage arm of a comparative study of 68 women who had a caesarean section, there were no reported complications from re-infusing salvaged blood. Unused salvaged blood from 15 women was analysed and found to contain fetal haemoglobin at a concentration of 1.8–2.0% in 20% of cases (3/15). These same women were also found to have fetal haemoglobin in maternal blood samples. No complications were reported using salvaged blood treated with a leukocyte depletion filter in a series of four reported cases. For more details, refer to the Sources of evidence.\n\nIn a controlled trial there was no significant difference in disseminated intravascular coagulation or rate of infection between women who received salvaged blood and women in the control group, who received standard transfusions.\n\nThe Specialist Advisors noted that the theoretical safety concerns include infusion of fetal cells, which could potentially cause haemolytic disease in future pregnancies. Advisors also noted the potential risk of amniotic fluid embolism.\n\nAndrew DillonChief ExecutiveNovember 2005', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of intraoperative blood cell salvage in obstetric procedures', December 2004.\n\n# Information for the public\n\nNICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'Changes since publication': 'NICE considered the evidence relating to the efficacy and safety of intraoperative blood cell salvage in obstetrics (IPG144) and for intraoperative red blood cell salvage during radical prostatectomy or radical cystectomy (NICE interventional procedure guidance 258) in response to concerns expressed about theoretical risks associated with the procedure. These concerns were the possibility of amniotic fluid embolism and haemolytic disease in future pregnancies when used in obstetrics, and reinfusion of malignant cells when used in radical prostatectomy/cystectomy.\n\nThe evidence relating to safety of cell salvage in these procedures was considered adequate and therefore NICE does not intend to review its use in other specific clinical situations unless notified of new indications for intraoperative cell salvage in which there may be new safety concerns.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt has been incorporated into the NICE pathway on caesarean section, along with other related guidance and products.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg144
35bfb910f4b11cbbcff52686ffb9f853416b961a	nice	Cryotherapy as a primary treatment for prostate cancer	Cryotherapy as a primary treatment for prostate cancer # Guidance Current evidence on the safety and efficacy of cryotherapy, measured by reduction of prostate-specific antigen (PSA) levels and biopsy findings, appears adequate to support the use of this procedure as a primary treatment in patients with prostate cancer provided that normal arrangements are in place for consent, audit and clinical governance. The effects of cryotherapy as a primary treatment for prostate cancer on quality of life and long-term survival remain uncertain. Clinicians should therefore ensure that patients understand the uncertainties and the alternative treatment options. They should provide them with clear written information and, in addition, use of the Institute's information for the public is recommended. Further research and audit should address quality of life, clinical outcomes and long-term survival.# The procedure # Indications Cryotherapy has been used for prostate cancer mainly as a salvage procedure for local recurrence following radiotherapy. More recently, it has been used as a primary treatment for patients with localised or locally advanced prostate cancer. Treatment options depend on the extent of the cancer. Current treatments for localised prostate cancer include watchful management, radiotherapy and radical prostatectomy. # Outline of the procedure Cryotherapy may be performed under general or regional anaesthesia. A warming catheter is initially inserted into the urethra to prevent it being damaged by cold. Cryoprobes are inserted into the prostate, using imaging for guidance. Temperature monitor probes may also be placed percutaneously through the perineum. Argon gas is then circulated through the cryoprobes, generating very low temperatures which freeze and destroy the affected tissue. Newer cryotherapy techniques allow these needles to be removed or repositioned so that the frozen zone conforms to the exact size and shape of the target tissue. After the procedure, a suprapubic catheter is inserted and left in place for 1–2 weeks, depending on the postvoid residual urine volume. # Efficacy The main outcomes reported by the studies were biopsy results and survival rates. In addition, different PSA values were used to define biochemical disease-free survival. In most of the studies, the procedure was used concomitantly with hormone therapy which may have an effect on PSA levels. One study of 975 patients reported a 5-year actuarial biochemical disease-free survival of 52% or 63%, depending on the PSA cut-off value (< 0.5 ng/ml and < 1.0 ng/ml, respectively). Another study of 590 patients reported a 7-year actuarial biochemical disease-free survival of between 62% and 76%, depending on the criteria used (PSA < 0.5 ng/ml and < 1.0 ng/ml, respectively). The proportion of patients with a negative biopsy was 87% (514/590) after a mean follow-up of 5 years. One non-randomised study reported that 6 months after standard cryosurgery or total cryosurgery (where the urethra was also frozen), 49% (24/49) and 96% (26/27) of patients respectively had a PSA level of between 0.0 and 2.0 ng/ml, compared with 73% (61/83) of patients after radical prostatectomy. Another study reported that 96% (213/223) of patients were satisfied with their cryotherapy treatment after a mean follow-up of 2 years. For more details, refer to the Sources of evidence. The Specialist Advisors stated that total ablation may not be achieved with this procedure and its effects on quality of life and survival are uncertain. # Safety The main complications were impotence, affecting between 72% (39/54) and 100% (76/76) of patients, and incontinence, affecting 1% (1/76) to 19% (10/54) of patients. However, not all studies reported the proportion of patients who had been impotent or incontinent before the cryotherapy treatment. Five studies, including a total of 1891 patients, reported that between 4% (3/76) and 15% (4/27) of patients required a transurethral resection after the cryotherapy procedure. Four studies reported fistula as a complication, affecting between less than 1% (2/590) and 2% (1/54) of patients. Other complications included urinary tract infection, scrotal swelling, pelvic pain, penile tingling and numbness, stricture, stone formation in the prostatic urethra, bladder perforation, paraphimosis and paraesthesia in the legs. For more details, refer to the Sources of evidence. The Specialist Advisors stated that the main potential adverse events included rectal injury and fistula, impotence, incontinence and urethral stricture. # Other comments In recommending that further research and audit should address long-term survival, it was noted that prostate cancer patients frequently die from unrelated causes. There are different types of cryotherapy device, and these may have different safety profiles. The technology for this procedure is continuing to evolve. The data were difficult to interpret due to the heterogeneous groups of patients in the studies.# Further information The Institute has issued guidance on urological cancer services, which includes prostate cancer. The Institute has also issued interventional procedures guidance on the use of cryotherapy for recurrent prostate cancer, laparoscopic radical prostatectomy and high-intensity focused ultrasound for prostate cancer. Further recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of cryotherapy as a primary treatment for prostate cancer', October 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Other NICE recommendations on cryotherapy for the treatment of prostate cancer The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on cryotherapy as a primary treatment for prostate cancer in November 2005. Further recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008, as follows: High intensity focused ultrasound (HIFU) and cryotherapy are not recommended for men with localised prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions. Clinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available. The IP guidance on cryotherapy as a primary treatment for prostate cancer remains current, and should be read in conjunction with the clinical guideline.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of cryotherapy, measured by reduction of prostate-specific antigen (PSA) levels and biopsy findings, appears adequate to support the use of this procedure as a primary treatment in patients with prostate cancer provided that normal arrangements are in place for consent, audit and clinical governance.\n\nThe effects of cryotherapy as a primary treatment for prostate cancer on quality of life and long-term survival remain uncertain. Clinicians should therefore ensure that patients understand the uncertainties and the alternative treatment options. They should provide them with clear written information and, in addition, use of the Institute's information for the public is recommended.\n\nFurther research and audit should address quality of life, clinical outcomes and long-term survival.", 'The procedure': '# Indications\n\nCryotherapy has been used for prostate cancer mainly as a salvage procedure for local recurrence following radiotherapy. More recently, it has been used as a primary treatment for patients with localised or locally advanced prostate cancer.\n\nTreatment options depend on the extent of the cancer. Current treatments for localised prostate cancer include watchful management, radiotherapy and radical prostatectomy.\n\n# Outline of the procedure\n\nCryotherapy may be performed under general or regional anaesthesia. A warming catheter is initially inserted into the urethra to prevent it being damaged by cold. Cryoprobes are inserted into the prostate, using imaging for guidance. Temperature monitor probes may also be placed percutaneously through the perineum. Argon gas is then circulated through the cryoprobes, generating very low temperatures which freeze and destroy the affected tissue. Newer cryotherapy techniques allow these needles to be removed or repositioned so that the frozen zone conforms to the exact size and shape of the target tissue. After the procedure, a suprapubic catheter is inserted and left in place for 1–2 weeks, depending on the postvoid residual urine volume.\n\n# Efficacy\n\nThe main outcomes reported by the studies were biopsy results and survival rates. In addition, different PSA values were used to define biochemical disease-free survival. In most of the studies, the procedure was used concomitantly with hormone therapy which may have an effect on PSA levels.\n\nOne study of 975 patients reported a 5-year actuarial biochemical disease-free survival of 52% or 63%, depending on the PSA cut-off value (< 0.5 ng/ml and < 1.0 ng/ml, respectively). Another study of 590 patients reported a 7-year actuarial biochemical disease-free survival of between 62% and 76%, depending on the criteria used (PSA < 0.5 ng/ml and < 1.0 ng/ml, respectively). The proportion of patients with a negative biopsy was 87% (514/590) after a mean follow-up of 5 years.\n\nOne non-randomised study reported that 6 months after standard cryosurgery or total cryosurgery (where the urethra was also frozen), 49% (24/49) and 96% (26/27) of patients respectively had a PSA level of between 0.0 and 2.0 ng/ml, compared with 73% (61/83) of patients after radical prostatectomy. Another study reported that 96% (213/223) of patients were satisfied with their cryotherapy treatment after a mean follow-up of 2 years. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that total ablation may not be achieved with this procedure and its effects on quality of life and survival are uncertain.\n\n# Safety\n\nThe main complications were impotence, affecting between 72% (39/54) and 100% (76/76) of patients, and incontinence, affecting 1% (1/76) to 19% (10/54) of patients. However, not all studies reported the proportion of patients who had been impotent or incontinent before the cryotherapy treatment. Five studies, including a total of 1891 patients, reported that between 4% (3/76) and 15% (4/27) of patients required a transurethral resection after the cryotherapy procedure. Four studies reported fistula as a complication, affecting between less than 1% (2/590) and 2% (1/54) of patients. Other complications included urinary tract infection, scrotal swelling, pelvic pain, penile tingling and numbness, stricture, stone formation in the prostatic urethra, bladder perforation, paraphimosis and paraesthesia in the legs. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that the main potential adverse events included rectal injury and fistula, impotence, incontinence and urethral stricture.\n\n# Other comments\n\nIn recommending that further research and audit should address long-term survival, it was noted that prostate cancer patients frequently die from unrelated causes.\n\nThere are different types of cryotherapy device, and these may have different safety profiles. The technology for this procedure is continuing to evolve.\n\nThe data were difficult to interpret due to the heterogeneous groups of patients in the studies.', 'Further information': "The Institute has issued guidance on urological cancer services, which includes prostate cancer. The Institute has also issued interventional procedures guidance on the use of cryotherapy for recurrent prostate cancer, laparoscopic radical prostatectomy and high-intensity focused ultrasound for prostate cancer.\n\nFurther recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of cryotherapy as a primary treatment for prostate cancer', October 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Other NICE recommendations on cryotherapy for the treatment of prostate cancer': 'The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on cryotherapy as a primary treatment for prostate cancer in November 2005.\n\nFurther recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008, as follows:\n\nHigh intensity focused ultrasound (HIFU) and cryotherapy are not recommended for men with localised prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions.\n\nClinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available. The IP guidance on cryotherapy as a primary treatment for prostate cancer remains current, and should be read in conjunction with the clinical guideline.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg145
1550f5cd570cb950b46ec6075f9e799d52ca1812	nice	Photodynamic therapy for localised inoperable endobronchial cancer	Photodynamic therapy for localised inoperable endobronchial cancer # Guidance Current evidence on the safety and efficacy of photodynamic therapy for localised inoperable endobronchial cancer appears adequate to support the use of this procedure provided that the normal arrangements are in place for audit and clinical governance. This procedure is a treatment option for patients with localised endobronchial cancer that is unsuitable for surgical resection. Clinicians should ensure that patients understand the aim of the treatment, especially when its purpose is palliation. Patients should also be informed of the alternative treatment options available. Clinicians should provide them with clear written information and, in addition, use of the Institute's information for the public is recommended. Further research and audit will be useful in clarifying the indications and benefits of this procedure.# The procedure # Indications Localised endobronchial (non-small-cell) lung cancer describes disease in which malignancy is confined within the bronchial wall, with no radiographic or endoscopic evidence of lymph node involvement. Patients for whom surgical resection may be considered unsuitable include those with bilateral lung cancer, impaired respiratory function because of chronic obstructive pulmonary disease or other conditions posing high operative risk, those who have had previous resection for lung cancer, and those who refuse surgery. The range of treatment options for lung cancer depends on the type and stage of the disease and the suitability of major surgery for the individual patient. Treatment options include laser ablation, endobronchial brachytherapy and external-beam radiation. # Outline of the procedure Photodynamic therapy (PDT) involves injection of a photosensitising agent, followed a few days later by photoradiation of the affected area through a bronchoscope. This aims to reduce tumour bulk, so reducing symptoms caused by bronchial obstruction. Endobronchial debridement of necrotic tumour is required, commonly 48 hours after each treatment. The procedure can be repeated if necessary. # Efficacy There were no randomised controlled or comparative trials comparing the efficacy of PDT with other treatment modalities. There was considerable heterogeneity among the studies included in the systematic reviews, with regard to both outcome measurements used and follow-up times reported. The complete remission rates following PDT ranged from 62% (16/26) to 85% (50/59) of lesions in different case series. Some subgroup analyses suggested that small lesions (in terms of diameter or surface area) respond to PDT better than larger lesions. Where reported in case series, 5-year survival ranged from 43% among 36 patients with poor pulmonary or cardiac function to 72% among 21 patients who were surgical candidates. Other studies reported reduction of airway obstruction and improvement in self-reported quality of life after PDT. For more details, refer to the Sources of evidence. The Specialist Advisors stated that there were no long-term comparative data on the efficacy of this procedure. # Safety In one systematic review, eight studies reported adverse events. Mild to moderate symptoms of photosensitivity were reported in all studies. Very severe toxicity resulting from photosensitivity occurred in a minority of patients undergoing PDT. Fatal haemoptysis within 1 month of treatment was recorded in 8% (3/38) of patients in one case series. Hypercapnic respiratory failure (requiring mechanical ventilation) occurred in 5% (2/38) and 4% (1/24) of patients following PDT. Some effects may be due to pre-existing pulmonary disease rather than the procedure. Other case series reported mild to moderate pulmonary events including short-term productive cough following PDT (the proportion of patients was not reported). For more details, refer to the Sources of evidence. The Specialist Advisors listed photosensitivity as the main complication. Other potential adverse events were tissue necrosis leading to bleeding, and fistula formation. # Other comments It was noted that a variety of laser systems is available and different dosage schedules may be used. These variations may have an effect on safety and efficacy. This procedure may be used in combination with other treatment modalities. The heterogeneous groups of patients included in the studies and reviews made interpretation of the data difficult.# Further information The Institute has issued guidance on the diagnosis and treatment of lung cancer. The Institute has also issued interventional procedures guidance on the use of photodynamic therapy for advanced bronchial carcinoma and cryotherapy for malignant endobronchial obstruction. Andrew DillonChief ExecutiveNovember 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedures overview of photodynamic therapy for localised, inoperable endobronchial cancer', November 2004. # Information for the public NICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of photodynamic therapy for localised inoperable endobronchial cancer appears adequate to support the use of this procedure provided that the normal arrangements are in place for audit and clinical governance.\n\nThis procedure is a treatment option for patients with localised endobronchial cancer that is unsuitable for surgical resection. Clinicians should ensure that patients understand the aim of the treatment, especially when its purpose is palliation. Patients should also be informed of the alternative treatment options available. Clinicians should provide them with clear written information and, in addition, use of the Institute's information for the public is recommended.\n\nFurther research and audit will be useful in clarifying the indications and benefits of this procedure.", 'The procedure': '# Indications\n\nLocalised endobronchial (non-small-cell) lung cancer describes disease in which malignancy is confined within the bronchial wall, with no radiographic or endoscopic evidence of lymph node involvement. Patients for whom surgical resection may be considered unsuitable include those with bilateral lung cancer, impaired respiratory function because of chronic obstructive pulmonary disease or other conditions posing high operative risk, those who have had previous resection for lung cancer, and those who refuse surgery.\n\nThe range of treatment options for lung cancer depends on the type and stage of the disease and the suitability of major surgery for the individual patient. Treatment options include laser ablation, endobronchial brachytherapy and external-beam radiation.\n\n# Outline of the procedure\n\nPhotodynamic therapy (PDT) involves injection of a photosensitising agent, followed a few days later by photoradiation of the affected area through a bronchoscope. This aims to reduce tumour bulk, so reducing symptoms caused by bronchial obstruction. Endobronchial debridement of necrotic tumour is required, commonly 48 hours after each treatment. The procedure can be repeated if necessary.\n\n# Efficacy\n\nThere were no randomised controlled or comparative trials comparing the efficacy of PDT with other treatment modalities. There was considerable heterogeneity among the studies included in the systematic reviews, with regard to both outcome measurements used and follow-up times reported. The complete remission rates following PDT ranged from 62% (16/26) to 85% (50/59) of lesions in different case series. Some subgroup analyses suggested that small lesions (in terms of diameter or surface area) respond to PDT better than larger lesions.\n\nWhere reported in case series, 5-year survival ranged from 43% among 36 patients with poor pulmonary or cardiac function to 72% among 21 patients who were surgical candidates. Other studies reported reduction of airway obstruction and improvement in self-reported quality of life after PDT. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that there were no long-term comparative data on the efficacy of this procedure.\n\n# Safety\n\nIn one systematic review, eight studies reported adverse events. Mild to moderate symptoms of photosensitivity were reported in all studies. Very severe toxicity resulting from photosensitivity occurred in a minority of patients undergoing PDT.\n\nFatal haemoptysis within 1 month of treatment was recorded in 8% (3/38) of patients in one case series. Hypercapnic respiratory failure (requiring mechanical ventilation) occurred in 5% (2/38) and 4% (1/24) of patients following PDT. Some effects may be due to pre-existing pulmonary disease rather than the procedure. Other case series reported mild to moderate pulmonary events including short-term productive cough following PDT (the proportion of patients was not reported). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors listed photosensitivity as the main complication. Other potential adverse events were tissue necrosis leading to bleeding, and fistula formation.\n\n# Other comments\n\nIt was noted that a variety of laser systems is available and different dosage schedules may be used. These variations may have an effect on safety and efficacy.\n\nThis procedure may be used in combination with other treatment modalities.\n\nThe heterogeneous groups of patients included in the studies and reviews made interpretation of the data difficult.', 'Further information': "The Institute has issued guidance on the diagnosis and treatment of lung cancer. The Institute has also issued interventional procedures guidance on the use of photodynamic therapy for advanced bronchial carcinoma and cryotherapy for malignant endobronchial obstruction.\n\nAndrew DillonChief ExecutiveNovember 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedures overview of photodynamic therapy for localised, inoperable endobronchial cancer', November 2004.\n\n# Information for the public\n\nNICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg137
6e25f5a9d8f032456843b8852ab9ec8408a330a2	nice	Laparoscopic nephrectomy (including nephroureterectomy)	Laparoscopic nephrectomy (including nephroureterectomy) # Guidance Current evidence on the safety and efficacy of laparoscopic nephrectomy (including nephroureterectomy) appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Patient selection is important when this procedure is being considered for the treatment of malignant disease. Long-term follow-up data are lacking, and clinicians are encouraged to collect data on rates of recurrence in patients with malignant disease.# The procedure # Indications Indications for nephrectomy (including nephroureterectomy) include renal cell or urethral cancer and benign conditions that lead to a poorly functioning or non-functioning kidney. These benign conditions may be due to or associated with symptomatic hydronephrosis, chronic infection, polycystic kidney disease, dysplastic kidney, hypertension and renal calculus. The standard treatment for an irreversibly damaged kidney or localised kidney cancer is an open nephrectomy. Under general anaesthesia, the kidney is removed through an incision in the loin or the front of the abdomen. # Outline of the procedure A transperitoneal or retroperitoneal approach may be used for laparoscopic nephrectomy. In the transperitoneal approach, the abdomen is insufflated with carbon dioxide through a trocar and then three or four small abdominal incisions are made. In the retroperitoneal approach, a small incision is made in the back and a dissecting balloon is inserted to create a retroperitoneal space. After the balloon is removed, the space is insufflated with carbon dioxide and two or three additional small incisions are made in the back for the laparoscopic instruments. The kidney is freed by laparoscopic dissection, and is then enclosed in a bag and removed through an appropriate incision or placed in an impermeable sac, morcellated and removed through one of the port sites. The ureter is sometimes removed along with the kidney (laparoscopic radical nephroureterectomy). Hand-assisted laparoscopic nephrectomy allows the surgeon to place one hand in the abdomen while maintaining the pneumoperitoneum required for laparoscopy. An additional small incision is made which is just large enough for the surgeon's hand, and an airtight 'sleeve' device is used to form a seal around the incision. # Efficacy One non-randomised comparative study of 100 patients with renal cell carcinoma reported that there was no statistically significant difference in the estimated 5-year disease-free survival rate for laparoscopic and open nephrectomy (95.5% versus 97.5%, respectively). A case series of 157 patients with renal cell carcinoma who had the laparoscopic procedure reported an estimated 5-year disease-free survival rate of 91%. Two non-randomised comparative studies, including 209 patients with upper urinary tract transitional cell carcinoma, reported no difference in recurrence rates between laparoscopic and open nephroureterectomy. Two non-randomised comparative studies found that significantly less analgesia was required after laparoscopic nephrectomy than after open surgery. In a further two non-randomised comparative studies, the mean hospital stay ranged from 5.2 days to 8.9 days for open surgery, compared with 3.4 days to 6.8 days for laparoscopic surgery (p < 0.001). In one study, the mean convalescence period was also significantly shorter for laparoscopic surgery: 23 days compared with 57 days for open surgery (p < 0.001). For more details, refer to the Sources of evidence. The Specialist Advisors did not express any concerns about the efficacy of this procedure when performed by trained operators. However, they noted that there was a lack of data from randomised controlled trials. # Safety Three non-randomised comparative studies reported complication rates for laparoscopic nephrectomy that were not significantly different from those for open nephrectomy. Six studies reported rates of conversion to open surgery: this occurred in 0% (0/54) to 10% (46/482) of procedures. The complications reported in a large case series of 482 procedures (461 patients) included bleeding in 5% (22/482), re-intervention in 3% (15/482) and bowel injury in less than 1% (3/482). Other complications reported in the studies included paralytic ileus in 3% (2/60) of patients; injury to arteries in 3% (2/60), the spleen in 2% (1/60) and the adrenal gland in 2% (1/60); and urinary tract infection in 1% (2/157). Two case series reported mortality rates of less than 1% (2/263) and 1% (2/157). For more details, refer to the Sources of evidence. The Specialist Advisors stated that potential adverse events included major haemorrhage from renal vessels, bowel injury and the need for conversion to open surgery. # Other comments It was noted that training and competence in laparoscopic techniques were important for surgeons undertaking this procedure.# Further information The Institute has produced guidance on laparoscopic live donor simple nephrectomy. Andrew DillonChief ExecutiveAugust 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of laparoscopic nephrectomy (including nephroureterectomy)', March 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It has been incorporated into the NICE pathway on chronic kidney disease, along with other related guidance and products. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of laparoscopic nephrectomy (including nephroureterectomy) appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nPatient selection is important when this procedure is being considered for the treatment of malignant disease. Long-term follow-up data are lacking, and clinicians are encouraged to collect data on rates of recurrence in patients with malignant disease.', 'The procedure': "# Indications\n\nIndications for nephrectomy (including nephroureterectomy) include renal cell or urethral cancer and benign conditions that lead to a poorly functioning or non-functioning kidney. These benign conditions may be due to or associated with symptomatic hydronephrosis, chronic infection, polycystic kidney disease, dysplastic kidney, hypertension and renal calculus.\n\nThe standard treatment for an irreversibly damaged kidney or localised kidney cancer is an open nephrectomy. Under general anaesthesia, the kidney is removed through an incision in the loin or the front of the abdomen.\n\n# Outline of the procedure\n\nA transperitoneal or retroperitoneal approach may be used for laparoscopic nephrectomy. In the transperitoneal approach, the abdomen is insufflated with carbon dioxide through a trocar and then three or four small abdominal incisions are made. In the retroperitoneal approach, a small incision is made in the back and a dissecting balloon is inserted to create a retroperitoneal space. After the balloon is removed, the space is insufflated with carbon dioxide and two or three additional small incisions are made in the back for the laparoscopic instruments. The kidney is freed by laparoscopic dissection, and is then enclosed in a bag and removed through an appropriate incision or placed in an impermeable sac, morcellated and removed through one of the port sites. The ureter is sometimes removed along with the kidney (laparoscopic radical nephroureterectomy).\n\nHand-assisted laparoscopic nephrectomy allows the surgeon to place one hand in the abdomen while maintaining the pneumoperitoneum required for laparoscopy. An additional small incision is made which is just large enough for the surgeon's hand, and an airtight 'sleeve' device is used to form a seal around the incision.\n\n# Efficacy\n\nOne non-randomised comparative study of 100 patients with renal cell carcinoma reported that there was no statistically significant difference in the estimated 5-year disease-free survival rate for laparoscopic and open nephrectomy (95.5% versus 97.5%, respectively). A case series of 157 patients with renal cell carcinoma who had the laparoscopic procedure reported an estimated 5-year disease-free survival rate of 91%.\n\nTwo non-randomised comparative studies, including 209 patients with upper urinary tract transitional cell carcinoma, reported no difference in recurrence rates between laparoscopic and open nephroureterectomy.\n\nTwo non-randomised comparative studies found that significantly less analgesia was required after laparoscopic nephrectomy than after open surgery. In a further two non-randomised comparative studies, the mean hospital stay ranged from 5.2 days to 8.9 days for open surgery, compared with 3.4 days to 6.8 days for laparoscopic surgery (p < 0.001). In one study, the mean convalescence period was also significantly shorter for laparoscopic surgery: 23 days compared with 57 days for open surgery (p < 0.001). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors did not express any concerns about the efficacy of this procedure when performed by trained operators. However, they noted that there was a lack of data from randomised controlled trials.\n\n# Safety\n\nThree non-randomised comparative studies reported complication rates for laparoscopic nephrectomy that were not significantly different from those for open nephrectomy. Six studies reported rates of conversion to open surgery: this occurred in 0% (0/54) to 10% (46/482) of procedures.\n\nThe complications reported in a large case series of 482 procedures (461 patients) included bleeding in 5% (22/482), re-intervention in 3% (15/482) and bowel injury in less than 1% (3/482). Other complications reported in the studies included paralytic ileus in 3% (2/60) of patients; injury to arteries in 3% (2/60), the spleen in 2% (1/60) and the adrenal gland in 2% (1/60); and urinary tract infection in 1% (2/157). Two case series reported mortality rates of less than 1% (2/263) and 1% (2/157). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that potential adverse events included major haemorrhage from renal vessels, bowel injury and the need for conversion to open surgery.\n\n# Other comments\n\nIt was noted that training and competence in laparoscopic techniques were important for surgeons undertaking this procedure.", 'Further information': "The Institute has produced guidance on laparoscopic live donor simple nephrectomy.\n\nAndrew DillonChief ExecutiveAugust 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of laparoscopic nephrectomy (including nephroureterectomy)', March 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt has been incorporated into the NICE pathway on chronic kidney disease, along with other related guidance and products.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg136
a977dbb7cff12e06a46e8c1571bd4d7a39008c7f	nice	HealOzone for the treatment of tooth decay (occlusal pit and fissure caries and root caries)	HealOzone for the treatment of tooth decay (occlusal pit and fissure caries and root caries) Evidence-based recommendations on using an ozone-releasing device (HealOzone) in people with tooth decay. # Guidance HealOzone is not recommended for the treatment of tooth decay (occlusal pit and fissure caries and root caries), except in well-designed randomised controlled trials.# Clinical need and practice Tooth decay (dental caries) is a chronic disease that can result in the localised and progressive demineralisation (loss of mineral content) of the hard surfaces of the tooth. It is a multistage process initiated by the local accumulation of cariogenic bacteria on the hard surfaces of the tooth. Cariogenic bacteria metabolise dietary carbohydrates to produce plaque acids, which cause demineralisation of the tooth enamel (non-cavitated dental caries). Without successful treatment, the demineralisation can extend into the dentine and eventually into the pulp (cavitated dental caries). Common symptoms of untreated cavitated dental caries are significant pain and discomfort, which can lead to disturbances in eating and loss of sleep. The progression of dental caries is a slow process in most people; at current levels of consumption of fermentable carbohydrates and fluoride exposure, most enamel lesions take more than 2 years to cavitate. A number of variables can affect progression time and the progression of dental caries may be more rapid in deciduous teeth because they are less well mineralised. The type of dental caries can be classified by its location: pit and fissure caries occurs in the pits (small depressions) and fissures (small grooves) of the occlusal (biting) surface of teeth, the palatal surfaces of the upper molars and the vestibular surface of the lower molars. Caries can also occur between the surfaces of adjoining contact areas of adjacent teeth. Root caries occurs in the area between the tooth and the receding gum. Primary dental caries is decay on a previously sound natural tooth. Secondary dental caries is decay at the margin of a restoration (filling); this often necessitates replacement of the filling (re-restoration). Carious lesions are first identified on the basis of clinical visual examination. Various techniques are used to diagnose and monitor progression or reversal of dental caries, although none have been well validated. In addition to visual examination and probing, X-rays and digital radiography can be used to estimate the depth of lesions or to identify lesions that are 'hidden' on visual examination. Lesions can be classed as soft, leathery or hard. Lesions that are progressing are classified as 'active' and those that have stopped progressing are described as 'arrested'. This distinction is clinically important because arrested lesions do not require any further preventive interventions. Adults in the UK have an average of 1.5 decayed or unsound teeth, and 55 per cent have one or more decayed or unsound teeth (Adult Dental Survey 1998). Despite a reduction in the mean number of decayed, missing and filled teeth over the past 25 years, there are still many people with significant dental caries, which is often linked to socioeconomic factors. Forty three percent of 5-year-olds and 57% of 8-year-olds have obvious tooth decay in deciduous teeth, and between 52% and 77% of children aged 8 to 15 years have obvious tooth decay in permanent teeth (Dental Health Survey of Children 2003). Root caries usually begins between the ages of 30 and 40 years and is most prevalent in elderly people. The treatment of dental caries depends on the severity of the lesion at presentation (whether or not it is cavitated) and on its location. People undergoing dental treatment routinely should receive instructions on good oral hygiene and dietary advice to reduce the consumption of fermentable carbohydrates. After treatment, the activity status of dental caries lesions is assessed at follow-up visits to determine whether further preventive treatment is necessary. Water fluoridation and topical fluoride delivery – in the form of toothpastes, mouth rinses, gels and varnishes – are the mainstay in the management of dental caries. The effectiveness of fluoride has been established by randomised controlled trials and summarised recently in a series of systematic reviews produced by members of the Cochrane Collaboration. Non-cavitated pit and fissure caries is currently managed by removing plaque and treating with topical fluorides (for example, toothpaste and mouth rinse) and pit and fissure sealants where appropriate. Cavitated pit and fissure caries is currently managed by removing plaque and tooth decay (using drills or air abrasion) and restorative treatment with a composite resin, glass-ionomer cement or amalgam. Amalgam is commonly used for filling posterior permanent teeth. The average lifetime of a restoration is about 8 years, although it varies with the size of the restorations. Non-cavitated root caries is currently managed by removing plaque and treating with topical fluorides (for example, toothpaste and mouth rinse), which may be sufficient to prevent progression where the tooth is accessible to cleaning. The management of cavitated root caries involves removing plaque and treating with fluoride. Restorative treatment with glass ionomer cements or resin-based fillings may be required.# The technology HealOzone is a medical device that is manufactured by KaVo and CE marked for the treatment of pit and fissure caries and root caries. The HealOzone treatment system comprises an ozone delivery device, a mineral reductant used by the dentist and a 'patient kit' (fluoride-containing toothpaste, mouthwash and mouth spray) for home use. The mineral reductant and patient kit are accessories to the ozone delivery device. The HealOzone device delivers ozone at a concentration of 2100 parts per million to the site of dental caries on the tooth surface for between 10 and 120 seconds to destroy the cariogenic microorganisms. A mineral reductant is then applied to the tooth to neutralise residual bacterial acid, remove any residual ozone and provide minerals for the remineralisation process. The patient then uses the fluoride-containing patient kit for several weeks to remineralise the tooth before returning to the dentist for assessment. HealOzone treatment may be repeated at intervals of 3 and 6 months if the caries has not reversed, or restorative treatment may be carried out. Lesions may also be treated with HealOzone before sealant placement (it is hypothesised that this improves sealant retention), and cavitated lesions may be treated before filling placement (it is hypothesised that this improves the longevity of restorations). The capital cost of the HealOzone device is £11,950 (excluding VAT), with annual maintenance costs of between £220 and £450, depending on the service contract. The average estimated cost of adding HealOzone to conventional treatment (excluding capital and maintenance costs) ranges from £18 to £21 per tooth, depending on the type of dental caries. HealOzone is not currently available on the NHS.# Evidence and interpretation The Appraisal Committee (Appendix A) considered evidence from a number of sources (see Appendix B). # Clinical effectiveness The clinical effectiveness of HealOzone treatment was compared with a control in a number of randomised controlled trials (RCTs), by comparing the number of dental caries lesions that reversed (for example, changing from leathery to hard) or progressed. Ten RCTs of HealOzone treatment of primary dental caries were included in the systematic review conducted by the Assessment Group. Studies of less than 6 months duration were excluded from the review on the basis of clinical advice that follow-up periods of less than 6 months were inadequate to assess caries progression. Seven RCTs (two PhD theses, one pilot study and four abstracts) evaluated the effect of HealOzone treatment on pit and fissure caries. Three RCTs (one published, one unpublished and one published in abstract only) evaluated the effect of HealOzone treatment on root caries. The studies were conducted in permanent teeth, with the exception of the study reported in one of the PhD theses. Two of the studies evaluated whether the addition of HealOzone treatment improved sealant retention: one in the treatment of pit and fissure caries, and another in the treatment of root caries. The Assessment Group noted a number of factors in the studies that made it difficult to assess the effectiveness of HealOzone treatment alone and prevented a quantitative synthesis of the results. Several studies (particularly those published in abstract only) did not fully report the methodology used; for example, it was not always clear whether the assessors of treatment outcome were blinded to the treatment group. Also, the data analysis was not necessarily appropriate. For example, analysing the data by lesion without taking into account the fact that measurements derived from two or more lesions in the same patient are not independent could introduce bias into the results. Study participants received repeat treatments at different timepoints in different studies and in some studies no repeat treatment was given. ## Non-cavitated pit and fissure caries The Assessment Group reported the results of five RCTs (one PhD thesis and four abstracts) that evaluated the effect of HealOzone treatment in adults with non-cavitated pit and fissure caries. The PhD thesis (n = 90; 258 lesions) reported that at 12 months in the HealOzone treatment group (ozone plus reductant) 7% of lesions had reversed, 57% remained stable and 36% had progressed, compared with 6% reversed, 49% stable and 46% progressed in the control group (reductant only). The mean change from baseline in clinical severity score at 12 months was not statistically significant (p = 0.112). There was no statistically significant difference in sealant retention between treatment groups at 12 months (33% had partial loss in the sealant margins in the HealOzone group compared with 30% in the control group). In three abstracts, the proportion of lesions reported as clinically reversed at 6 to 12 months follow-up ranged from 87% to 99% in the HealOzone treatment group. All studies reported that no significant clinical changes were observed in the control group, but no data were provided. The fourth abstract (n = 38; 76 lesions) reported that all lesions were hard at 3 months (that is, all caries had reversed) in the HealOzone treatment group (air abrasion, ozone, mineral wash plus glass ionomer sealant); reversal rates were not reported in the control group (conventional drilling and filling). The Assessment Group noted that the results of these studies should be interpreted with caution because the lack of detail meant that their methodology could not be easily assessed. ## Cavitated pit and fissure caries A small pilot study reported in the PhD thesis described in Section 4.1.4 (n = 8; 17 lesions per group) evaluated the effect of HealOzone treatment on cavitated pit and fissure caries. It reported statistically significant improvements in hardness and visual scores (p 0.05). ## Deciduous dentition The study in the second PhD thesis (n = 21; 74 lesions) evaluated the effectiveness of HealOzone treatment in non-cavitated pit and fissure caries in deciduous teeth (children aged 7 to 9 years). Data were presented graphically; at the 12-month follow-up, there was a small reduction in the severity of dental caries in the HealOzone treatment group (ozone plus reductant), and an increase in severity scores in the control group (reductant only). There was a statistically significant change in clinical severity scores with treatment over time (p < 0.01). ## Non-cavitated root caries Three RCTs evaluated the effectiveness of HealOzone treatment for non-cavitated root caries; one published in full, one unpublished and one published only in abstract form. In the published study two lesions in each of 89 participants were randomised to treatment or control; 89 lesions per group. This study reported that 98% of lesions in the HealOzone treatment group (ozone application, reductant plus patient kit) became hard at 12 months compared with 1% in the control group (air treatment, reductant plus patient kit). The 21-month data from this study reported that 100% of lesions became hard with HealOzone treatment compared with 8% of lesions becoming hard, 80% remaining leathery and 12% becoming soft in the control group. The abstract (n = 260 with two lesions each; 260 lesions per group) reported that 80% of soft lesions had reversed from clinical severity index 4 to 3 and that 94% of leathery lesions became hard and arrested in the HealOzone treatment group (ozone application) at 6 months. There were no statistically significant changes in lesion severity for either type of lesion in the control group (no treatment). The unpublished full-text study (n = 79; 220 lesions, the numbers in each group were not reported) investigated the effectiveness of HealOzone treatment (cleaning, ozone and reductant, with or without sealant) in cavitated and non-cavitated root caries at 12 months follow-up. The results for cavitated and non-cavitated lesions could not be disaggregated. Overall, HealOzone treatment was associated with a statistically significant reversal of dental caries compared with the control treatment (reductant, with or without sealant) (p < 0.001). In the treatment group 99% of lesions improved (47% lesions became hard, and 52% became less severe), compared with 12% (none became hard) in the control group. Sealant retention was also statistically significantly improved: 61% in the HealOzone group compared with 42% in the control group (p < 0.05). ## Cavitated root caries Although the unpublished study described in Section 4.1.10 did not present separate data for cavitated and non-cavitated root caries, it was reported that the percentage of cavitated lesions in the HealOzone group that became hard decreased from 9% at 1 month to 1% at 9 months follow-up. No results were reported for the control group. ## Evidence from clinical and patient experts The Committee heard from experts that, although HealOzone treatment sterilises the surface of the tooth, microorganisms will immediately start to recolonise the area and will be well-established about 2 weeks after HealOzone treatment. The experts expressed concerns about the clinical trials that reported strongly favourable results. Their concerns included the unexpectedly poor performance of the controls, problems in the accurate diagnosis of the severity of dental caries and the absence of objective outcome measures. # Cost effectiveness No published economic evaluations were identified on HealOzone treatment of dental caries. The manufacturer submitted an economic model. The Assessment Group developed a second model, but argued that, given the current state of the clinical effectiveness evidence, economic analysis is premature and the model should therefore be taken as illustrative only. The Assessment Group's model is therefore not described further here. The submission from the manufacturer of the device assessed the cost effectiveness of adding HealOzone to conventional treatment that did not include preventive treatment. Effectiveness data for the addition of HealOzone treatment were based on average reversal rates of dental caries reported in the RCTs for non-cavitated (93.3%) and cavitated pit and fissure caries (79%), and for root caries (84.5%). The effectiveness of conventional treatment was based on the average annual progression rate of dental caries reported in clinical studies that were excluded from the Assessment Group's systematic review. The additional cost of HealOzone treatment per filling avoided was £9.58 in non-cavitated pit and fissure caries, £11.63 in cavitated pit and fissure caries and £5.18 in root caries. # Consideration of the evidence The Committee reviewed the evidence available on the clinical and cost effectiveness of HealOzone treatment of tooth decay, having considered evidence on the nature of the condition and the value placed on the benefits of HealOzone by people with tooth decay, those who represent them, and clinical experts. It was also mindful of the need to ensure that its advice took account of the effective use of NHS resources. The Committee considered the mode by whichdental cariesis reversed or arrested by HealOzone treatment. It accepted the evidence presented in the submission that ozone eliminated most microorganisms. However, given the testimony of clinical experts and lack of evidence to the contrary, the Committee concluded that it was logical that microorganisms would immediately start to recolonise the area and become well-established soon after HealOzone treatment. It considered the hypothesis that ozone could remove proteins in carious lesions by oxidation of amino acids, which could in turn enable remineralisation in the presence of the mineral reductant. However, the Committee noted a lack of evidence to support this theory. The Committee considered the evidence in which patients in the intervention and control arm received fluoride treatment (mineral reductant and the patient kit). The Committee was aware that many of the measures used in the RCTs to monitor caries are not well validated and are unreliable. It discussed the validity of the evidence that reported little or no effect in the control group of the fluoride comparator treatment. The Committee noted that experts said they would have expected to see higher rates of caries reversal from fluoride treatment in the control arms. The Committee concluded that, in light of these concerns, the evidence could not be considered reliable. The Committee accepted the Assessment Group's rationale for not examining the submitted trials of less than 6 months duration; the Committee agreed that shorter follow-up periods were inadequate to assess caries progress. Of the RCTs of HealOzone for non-cavitated pit and fissure caries that were of more than 6 months duration, the Committee took into consideration the fact that the non-significant results in the PhD thesis conflicted with the significant results of the abstracts. However, given the lower reliability of abstracts, the lack of information reported and the concerns over the robustness of the methodology used, it concluded that the benefits of HealOzone for non-cavitated pit and fissure caries had not been adequately demonstrated. Similarly, given the methodological concerns and the small sample size of the pilot studies in non-cavitated pit and fissure caries in deciduous teeth and cavitated pit and fissure caries in permanent teeth, the Committee concluded there is insufficient evidence to recommend this technology in these subgroups and further research is required. For the reasons expressed in 4.3.3, the Committee concluded that the evidence from RCTs of cavitated root caries was unreliable, and that HealOzone should not be recommended for the treatment of cavitated root caries. In light of the Committee's conclusion that the evidence from the RCTs was unreliable, the Committee did not discuss the findings of the cost-effectiveness evaluations. In summary, the Committee concluded that there was insufficient evidence on the effectiveness of HealOzone treatment for this technology to be recommended, except as part of well-designed RCTs.# Recommendations for further research On the basis of the current evidence, the place of HealOzone in the treatment or management of dental caries is not proven. If this technology is to be considered for use within the NHS, further research is needed to provide evidence of its clinical and cost effectiveness compared with current best practice. Such research should include large-scale RCTs, use validated methods for the diagnosis and assessment of dental caries, and incorporate appropriate statistical methods for the analysis of dependent data within patients. It will also need to show evidence of effectiveness on patient-centred outcomes (for example, pain and numbers of fillings and tooth extractions) to assess both long-term benefits and effects on quality of life.# Implications for the NHS HealOzone is not currently available on the NHS, so this guidance is not expected to lead to a change in NHS expenditure or have any impact on other NHS resources.# Related guidance Dental recall: recall interval between routine dental examinations. NICE Clinical Guideline No. 19 (issued October 2004).# Review of guidance The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review. The guidance on this technology will be considered for review in July 2008. Consideration will be given to an earlier review if the Institute is made aware of important new evidence that may impact on this guidance before this date. Andrew DillonChief ExecutiveJuly 2005# Changes after publication March 2014: minor maintenance March 2012: minor maintenance# About this guidance NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.	{'Guidance': 'HealOzone is not recommended for the treatment of tooth decay (occlusal pit and fissure caries and root caries), except in well-designed randomised controlled trials.', 'Clinical need and practice ': "Tooth decay (dental caries) is a chronic disease that can result in the localised and progressive demineralisation (loss of mineral content) of the hard surfaces of the tooth. It is a multistage process initiated by the local accumulation of cariogenic bacteria on the hard surfaces of the tooth. Cariogenic bacteria metabolise dietary carbohydrates to produce plaque acids, which cause demineralisation of the tooth enamel (non-cavitated dental caries). Without successful treatment, the demineralisation can extend into the dentine and eventually into the pulp (cavitated dental caries). Common symptoms of untreated cavitated dental caries are significant pain and discomfort, which can lead to disturbances in eating and loss of sleep.\n\nThe progression of dental caries is a slow process in most people; at current levels of consumption of fermentable carbohydrates and fluoride exposure, most enamel lesions take more than 2\xa0years to cavitate. A number of variables can affect progression time and the progression of dental caries may be more rapid in deciduous teeth because they are less well mineralised.\n\nThe type of dental caries can be classified by its location: pit and fissure caries occurs in the pits (small depressions) and fissures (small grooves) of the occlusal (biting) surface of teeth, the palatal surfaces of the upper molars and the vestibular surface of the lower molars. Caries can also occur between the surfaces of adjoining contact areas of adjacent teeth. Root caries occurs in the area between the tooth and the receding gum. Primary dental caries is decay on a previously sound natural tooth. Secondary dental caries is decay at the margin of a restoration (filling); this often necessitates replacement of the filling (re-restoration).\n\nCarious lesions are first identified on the basis of clinical visual examination. Various techniques are used to diagnose and monitor progression or reversal of dental caries, although none have been well validated. In addition to visual examination and probing, X-rays and digital radiography can be used to estimate the depth of lesions or to identify lesions that are 'hidden' on visual examination. Lesions can be classed as soft, leathery or hard. Lesions that are progressing are classified as 'active' and those that have stopped progressing are described as 'arrested'. This distinction is clinically important because arrested lesions do not require any further preventive interventions.\n\nAdults in the UK have an average of 1.5 decayed or unsound teeth, and 55\xa0per cent have one or more decayed or unsound teeth (Adult Dental Survey 1998). Despite a reduction in the mean number of decayed, missing and filled teeth over the past 25\xa0years, there are still many people with significant dental caries, which is often linked to socioeconomic factors. Forty three percent of 5-year-olds and 57% of 8-year-olds have obvious tooth decay in deciduous teeth, and between 52% and 77% of children aged 8 to 15 years have obvious tooth decay in permanent teeth (Dental Health Survey of Children 2003). Root caries usually begins between the ages of 30 and 40 years and is most prevalent in elderly people.\n\nThe treatment of dental caries depends on the severity of the lesion at presentation (whether or not it is cavitated) and on its location. People undergoing dental treatment routinely should receive instructions on good oral hygiene and dietary advice to reduce the consumption of fermentable carbohydrates. After treatment, the activity status of dental caries lesions is assessed at follow-up visits to determine whether further preventive treatment is necessary.\n\nWater fluoridation and topical fluoride delivery – in the form of toothpastes, mouth rinses, gels and varnishes – are the mainstay in the management of dental caries. The effectiveness of fluoride has been established by randomised controlled trials and summarised recently in a series of systematic reviews produced by members of the Cochrane Collaboration.\n\nNon-cavitated pit and fissure caries is currently managed by removing plaque and treating with topical fluorides (for example, toothpaste and mouth rinse) and pit and fissure sealants where appropriate.\n\nCavitated pit and fissure caries is currently managed by removing plaque and tooth decay (using drills or air abrasion) and restorative treatment with a composite resin, glass-ionomer cement or amalgam. Amalgam is commonly used for filling posterior permanent teeth. The average lifetime of a restoration is about 8 years, although it varies with the size of the restorations.\n\nNon-cavitated root caries is currently managed by removing plaque and treating with topical fluorides (for example, toothpaste and mouth rinse), which may be sufficient to prevent progression where the tooth is accessible to cleaning.\n\nThe management of cavitated root caries involves removing plaque and treating with fluoride. Restorative treatment with glass ionomer cements or resin-based fillings may be required.", 'The technology': "HealOzone is a medical device that is manufactured by KaVo and CE marked for the treatment of pit and fissure caries and root caries. The HealOzone treatment system comprises an ozone delivery device, a mineral reductant used by the dentist and a 'patient kit' (fluoride-containing toothpaste, mouthwash and mouth spray) for home use. The mineral reductant and patient kit are accessories to the ozone delivery device.\n\nThe HealOzone device delivers ozone at a concentration of 2100\xa0parts per million to the site of dental caries on the tooth surface for between 10 and 120\xa0seconds to destroy the cariogenic microorganisms. A mineral reductant is then applied to the tooth to neutralise residual bacterial acid, remove any residual ozone and provide minerals for the remineralisation process. The patient then uses the fluoride-containing patient kit for several weeks to remineralise the tooth before returning to the dentist for assessment. HealOzone treatment may be repeated at intervals of 3 and 6\xa0months if the caries has not reversed, or restorative treatment may be carried out.\n\nLesions may also be treated with HealOzone before sealant placement (it is hypothesised that this improves sealant retention), and cavitated lesions may be treated before filling placement (it is hypothesised that this improves the longevity of restorations).\n\nThe capital cost of the HealOzone device is £11,950 (excluding VAT), with annual maintenance costs of between £220 and £450, depending on the service contract. The average estimated cost of adding HealOzone to conventional treatment (excluding capital and maintenance costs) ranges from £18 to £21 per tooth, depending on the type of dental caries. HealOzone is not currently available on the NHS.", 'Evidence and interpretation ': "The Appraisal Committee (Appendix A) considered evidence from a number of sources (see Appendix B).\n\n# Clinical effectiveness\n\nThe clinical effectiveness of HealOzone treatment was compared with a control in a number of randomised controlled trials (RCTs), by comparing the number of dental caries lesions that reversed (for example, changing from leathery to hard) or progressed.\n\nTen RCTs of HealOzone treatment of primary dental caries were included in the systematic review conducted by the Assessment Group. Studies of less than 6\xa0months duration were excluded from the review on the basis of clinical advice that follow-up periods of less than 6\xa0months were inadequate to assess caries progression. Seven RCTs (two PhD theses, one pilot study [included in one of the theses] and four abstracts) evaluated the effect of HealOzone treatment on pit and fissure caries. Three RCTs (one published, one unpublished and one published in abstract only) evaluated the effect of HealOzone treatment on root caries. The studies were conducted in permanent teeth, with the exception of the study reported in one of the PhD theses. Two of the studies evaluated whether the addition of HealOzone treatment improved sealant retention: one in the treatment of pit and fissure caries, and another in the treatment of root caries.\n\nThe Assessment Group noted a number of factors in the studies that made it difficult to assess the effectiveness of HealOzone treatment alone and prevented a quantitative synthesis of the results. Several studies (particularly those published in abstract only) did not fully report the methodology used; for example, it was not always clear whether the assessors of treatment outcome were blinded to the treatment group. Also, the data analysis was not necessarily appropriate. For example, analysing the data by lesion without taking into account the fact that measurements derived from two or more lesions in the same patient are not independent could introduce bias into the results. Study participants received repeat treatments at different timepoints in different studies and in some studies no repeat treatment was given.\n\n## Non-cavitated pit and fissure caries\n\nThe Assessment Group reported the results of five RCTs (one PhD thesis and four abstracts) that evaluated the effect of HealOzone treatment in adults with non-cavitated pit and fissure caries. The PhD thesis (n\xa0=\xa090; 258 lesions) reported that at 12\xa0months in the HealOzone treatment group (ozone plus reductant) 7% of lesions had reversed, 57% remained stable and 36% had progressed, compared with 6% reversed, 49% stable and 46% progressed in the control group (reductant only). The mean change from baseline in clinical severity score at 12\xa0months was not statistically significant (p\xa0=\xa00.112). There was no statistically significant difference in sealant retention between treatment groups at 12\xa0months (33% had partial loss in the sealant margins in the HealOzone group compared with 30% in the control group).\n\nIn three abstracts, the proportion of lesions reported as clinically reversed at 6\xa0to\xa012\xa0months follow-up ranged from 87% to 99% in the HealOzone treatment group. All studies reported that no significant clinical changes were observed in the control group, but no data were provided. The fourth abstract (n\xa0=\xa038; 76\xa0lesions) reported that all lesions were hard at 3\xa0months (that is, all caries had reversed) in the HealOzone treatment group (air abrasion, ozone, mineral wash plus glass ionomer sealant); reversal rates were not reported in the control group (conventional drilling and filling). The Assessment Group noted that the results of these studies should be interpreted with caution because the lack of detail meant that their methodology could not be easily assessed.\n\n## Cavitated pit and fissure caries\n\nA small pilot study reported in the PhD thesis described in Section 4.1.4 (n\xa0=\xa08; 17 lesions per group) evaluated the effect of HealOzone treatment on cavitated pit and fissure caries. It reported statistically significant improvements in hardness and visual scores (p\xa0<\xa00.05) in the HealOzone group compared with the control group and no significant differences between groups in cavitation score, colour and perceived treatment need (p\xa0>\xa00.05).\n\n## Deciduous dentition\n\nThe study in the second PhD thesis (n\xa0=\xa021; 74 lesions) evaluated the effectiveness of HealOzone treatment in non-cavitated pit and fissure caries in deciduous teeth (children aged 7 to 9\xa0years). Data were presented graphically; at the 12-month follow-up, there was a small reduction in the severity of dental caries in the HealOzone treatment group (ozone plus reductant), and an increase in severity scores in the control group (reductant only). There was a statistically significant change in clinical severity scores with treatment over time (p\xa0<\xa00.01).\n\n## Non-cavitated root caries\n\nThree RCTs evaluated the effectiveness of HealOzone treatment for non-cavitated root caries; one published in full, one unpublished and one published only in abstract form. In the published study two lesions in each of 89 participants were randomised to treatment or control; 89 lesions per group. This study reported that 98% of lesions in the HealOzone treatment group (ozone application, reductant plus patient kit) became hard at 12 months compared with 1% in the control group (air treatment, reductant plus patient kit). The 21-month data from this study reported that 100% of lesions became hard with HealOzone treatment compared with 8% of lesions becoming hard, 80% remaining leathery and 12% becoming soft in the control group.\n\nThe abstract (n\xa0=\xa0260 with two lesions each; 260 lesions per group) reported that 80% of soft lesions had reversed from clinical severity index 4 to 3 and that 94% of leathery lesions became hard and arrested in the HealOzone treatment group (ozone application) at 6\xa0months. There were no statistically significant changes in lesion severity for either type of lesion in the control group (no treatment).\n\nThe unpublished full-text study (n\xa0=\xa079; 220 lesions, the numbers in each group were not reported) investigated the effectiveness of HealOzone treatment (cleaning, ozone and reductant, with or without sealant) in cavitated and non-cavitated root caries at 12\xa0months follow-up. The results for cavitated and non-cavitated lesions could not be disaggregated. Overall, HealOzone treatment was associated with a statistically significant reversal of dental caries compared with the control treatment (reductant, with or without sealant) (p\xa0<\xa00.001). In the treatment group 99% of lesions improved (47% lesions became hard, and 52% became less severe), compared with 12% (none became hard) in the control group. Sealant retention was also statistically significantly improved: 61% in the HealOzone group compared with 42% in the control group (p\xa0<\xa00.05).\n\n## Cavitated root caries\n\nAlthough the unpublished study described in Section 4.1.10 did not present separate data for cavitated and non-cavitated root caries, it was reported that the percentage of cavitated lesions in the HealOzone group that became hard decreased from 9% at 1\xa0month to 1% at 9\xa0months follow-up. No results were reported for the control group.\n\n## Evidence from clinical and patient experts\n\nThe Committee heard from experts that, although HealOzone treatment sterilises the surface of the tooth, microorganisms will immediately start to recolonise the area and will be well-established about 2\xa0weeks after HealOzone treatment.\n\nThe experts expressed concerns about the clinical trials that reported strongly favourable results. Their concerns included the unexpectedly poor performance of the controls, problems in the accurate diagnosis of the severity of dental caries and the absence of objective outcome measures.\n\n# Cost effectiveness\n\nNo published economic evaluations were identified on HealOzone treatment of dental caries. The manufacturer submitted an economic model. The Assessment Group developed a second model, but argued that, given the current state of the clinical effectiveness evidence, economic analysis is premature and the model should therefore be taken as illustrative only. The Assessment Group's model is therefore not described further here.\n\nThe submission from the manufacturer of the device assessed the cost effectiveness of adding HealOzone to conventional treatment that did not include preventive treatment. Effectiveness data for the addition of HealOzone treatment were based on average reversal rates of dental caries reported in the RCTs for non-cavitated (93.3%) and cavitated pit and fissure caries (79%), and for root caries (84.5%). The effectiveness of conventional treatment was based on the average annual progression rate of dental caries reported in clinical studies that were excluded from the Assessment Group's systematic review. The additional cost of HealOzone treatment per filling avoided was £9.58 in non-cavitated pit and fissure caries, £11.63 in cavitated pit and fissure caries and £5.18 in root caries.\n\n# Consideration of the evidence\n\nThe Committee reviewed the evidence available on the clinical and cost effectiveness of HealOzone treatment of tooth decay, having considered evidence on the nature of the condition and the value placed on the benefits of HealOzone by people with tooth decay, those who represent them, and clinical experts. It was also mindful of the need to ensure that its advice took account of the effective use of NHS resources.\n\nThe Committee considered the mode by whichdental cariesis reversed or arrested by HealOzone treatment. It accepted the evidence presented in the submission that ozone eliminated most microorganisms. However, given the testimony of clinical experts and lack of evidence to the contrary, the Committee concluded that it was logical that microorganisms would immediately start to recolonise the area and become well-established soon after HealOzone treatment. It considered the hypothesis that ozone could remove proteins in carious lesions by oxidation of amino acids, which could in turn enable remineralisation in the presence of the mineral reductant. However, the Committee noted a lack of evidence to support this theory.\n\nThe Committee considered the evidence in which patients in the intervention and control arm received fluoride treatment (mineral reductant and the patient kit). The Committee was aware that many of the measures used in the RCTs to monitor caries are not well validated and are unreliable. It discussed the validity of the evidence that reported little or no effect in the control group of the fluoride comparator treatment. The Committee noted that experts said they would have expected to see higher rates of caries reversal from fluoride treatment in the control arms. The Committee concluded that, in light of these concerns, the evidence could not be considered reliable.\n\nThe Committee accepted the Assessment Group's rationale for not examining the submitted trials of less than 6 months duration; the Committee agreed that shorter follow-up periods were inadequate to assess caries progress. Of the RCTs of HealOzone for non-cavitated pit and fissure caries that were of more than 6\xa0months duration, the Committee took into consideration the fact that the non-significant results in the PhD thesis conflicted with the significant results of the abstracts. However, given the lower reliability of abstracts, the lack of information reported and the concerns over the robustness of the methodology used, it concluded that the benefits of HealOzone for non-cavitated pit and fissure caries had not been adequately demonstrated. Similarly, given the methodological concerns and the small sample size of the pilot studies in non-cavitated pit and fissure caries in deciduous teeth and cavitated pit and fissure caries in permanent teeth, the Committee concluded there is insufficient evidence to recommend this technology in these subgroups and further research is required.\n\nFor the reasons expressed in 4.3.3, the Committee concluded that the evidence from RCTs of cavitated root caries was unreliable, and that HealOzone should not be recommended for the treatment of cavitated root caries.\n\nIn light of the Committee's conclusion that the evidence from the RCTs was unreliable, the Committee did not discuss the findings of the cost-effectiveness evaluations.\n\nIn summary, the Committee concluded that there was insufficient evidence on the effectiveness of HealOzone treatment for this technology to be recommended, except as part of well-designed RCTs.", 'Recommendations for further research': 'On the basis of the current evidence, the place of HealOzone in the treatment or management of dental caries is not proven. If this technology is to be considered for use within the NHS, further research is needed to provide evidence of its clinical and cost effectiveness compared with current best practice. Such research should include large-scale RCTs, use validated methods for the diagnosis and assessment of dental caries, and incorporate appropriate statistical methods for the analysis of dependent data within patients. It will also need to show evidence of effectiveness on patient-centred outcomes (for example, pain and numbers of fillings and tooth extractions) to assess both long-term benefits and effects on quality of life.', 'Implications for the NHS ': 'HealOzone is not currently available on the NHS, so this guidance is not expected to lead to a change in NHS expenditure or have any impact on other NHS resources.', 'Related guidance': 'Dental recall: recall interval between routine dental examinations.\n NICE Clinical Guideline No. 19 (issued October\xa02004).', 'Review of guidance': 'The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review.\n\nThe guidance on this technology will be considered for review in July\xa02008. Consideration will be given to an earlier review if the Institute is made aware of important new evidence that may impact on this guidance before this date.\n\nAndrew DillonChief ExecutiveJuly 2005', 'Changes after publication': 'March 2014: minor maintenance\n\nMarch 2012: minor maintenance', 'About this guidance': 'NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales.\n\nWe have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.'}	https://www.nice.org.uk/guidance/ta92	Evidence-based recommendations on using an ozone-releasing device (HealOzone) in people with tooth decay.
5f7d359b38b5d194c73758d50a0cf3efc81feb91	nice	Low dose rate brachytherapy for localised prostate cancer	Low dose rate brachytherapy for localised prostate cancer # Guidance Current evidence on the safety and short- to medium-term efficacy of low dose rate brachytherapy for localised prostate cancer appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. Most of the evidence on the efficacy of low dose rate brachytherapy for localised prostate cancer relates to the reduction of prostate-specific antigen (PSA) levels and to biopsy findings. The effects on quality of life and long-term survival remain uncertain. Clinicians should ensure that patients understand these uncertainties and the alternative treatment options. Use of the Institute's information for the public is recommended. A multidisciplinary team should be involved in the planning and use of this procedure. The Institute has issued a cancer service guideline on improving outcomes in urological cancers. Further research and audit should address quality of life, clinical outcomes and long-term survival.# The procedure # Indications Treatment options for prostate cancer depend on whether the disease is localised to the prostate gland. Current management options for localised prostate cancer include radiotherapy, radical prostatectomy and 'watchful waiting'. Radiation therapy can take the form of external-beam radiotherapy or brachytherapy. Brachytherapy may be given at either low or high dose rates. Low dose rate brachytherapy may be used alone (monotherapy) or in combination with external-beam radiotherapy. # Outline of the procedure Low dose brachytherapy is a form of radiotherapy in which radiation is delivered directly to the prostate gland by small radioactive pellets (called seeds). Under general or spinal anaesthesia and ultrasound guidance, the seeds are inserted via needles passed through the skin of the perineum. In low dose rate brachytherapy, the seeds are left in place permanently and emit low-dose radiation over several weeks or months. # Efficacy The literature search found no randomised controlled trials that compared low dose rate brachytherapy with other kinds of treatment. Evaluation of the effectiveness of brachytherapy was made difficult by the diversity of the techniques used, the patient selection criteria applied and the different follow-up intervals reported. A recent large cohort study that compared almost 3000 patients undergoing low dose rate brachytherapy (either as monotherapy or combined with external-beam radiotherapy) with external-beam radiotherapy (> 72 Gy) or radical prostatectomy, found no difference in biochemical-recurrence-free survival between the three treatments at 5 or 7 years follow-up. In a comparative study in which 869 patients were treated with low dose rate brachytherapy, a 0.5 ng/ml PSA nadir level was reached in 86% (748/869) of patients after therapy. No comparison of long-term effects could be made because the outcomes for patients treated with radical prostatectomy were not recorded beyond 2 years. In a comparative study involving 1819 patients, overall survival at median follow-up of 58 months in patients with T1 or T2 cancer was found to be similar among those undergoing low dose rate brachytherapy (93%; 679/733 patients), radical prostatectomy (97%; 721/746 patients) and external-beam radiotherapy (96%; 325/340 patients). In another study, physical function scores in 92 patients treated with low dose rate brachytherapy and 327 patients treated with radical prostatectomy showed no significant changes from baseline in either group at 24 months. For more details, refer to the Sources of evidence. The Specialist Advisors considered low dose rate brachytherapy to be an established procedure and stated that the results are comparable with those achieved with surgery or external-beam radiotherapy in well-selected patients. # Safety Complications were generally not well reported, but included irritative/obstructive urinary symptoms, rectal symptoms and sexual dysfunction. In one study involving 869 patients undergoing low dose rate brachytherapy, the impotence rate was 10–15%, compared with 45% in 208 patients undergoing radical prostatectomy. The incontinence rate was less than 1% in both groups. Two case series included in a Health Technology Assessment Review reported disease-specific quality of life to be lower in patients receiving brachytherapy than in both those receiving external-beam radiotherapy alone and those in a healthy population. However, this review did not differentiate between low dose rate and high dose rate brachytherapy. For more details, refer to the Sources of evidence. The Specialist Advisors noted potential complications such as incontinence, infection and erectile dysfunction. # Other comments The data are difficult to interpret because of the other treatment modalities often used alongside this procedure. In recommending that further research and audit should address long-term survival, it was noted that men with prostate cancer often die from unrelated causes. It was also noted that the appropriate length of long-term follow-up would depend on the stage and grade of the tumour.# Further information The Institute has issued interventional procedure guidance on laparoscopic radical prostatectomy, high-intensity ultrasound for prostate cancer and cryotherapy for recurrent prostate cancer. It is also preparing guidance on high dose rate brachytherapy . The Institute is also developing a clinical guideline: Prostate cancer: diagnosis and treatment . Andrew DillonChief ExecutiveJuly 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of low dose rate brachytherapy for localised prostate cancer', January 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Other NICE recommendations on brachytherapy for the treatment of prostate cancer Further recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008, as follows: Brachytherapy is not recommended for men with high-risk localised prostate cancer. Clinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available. The IP guidance on low dose rate brachytherapy for localised prostate cancer remains current, and should be read in conjunction with the clinical guideline.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It has been incorporated into the NICE pathway on prostate cancer, along with other related guidance and products. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and short- to medium-term efficacy of low dose rate brachytherapy for localised prostate cancer appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nMost of the evidence on the efficacy of low dose rate brachytherapy for localised prostate cancer relates to the reduction of prostate-specific antigen (PSA) levels and to biopsy findings. The effects on quality of life and long-term survival remain uncertain. Clinicians should ensure that patients understand these uncertainties and the alternative treatment options. Use of the Institute's information for the public is recommended.\n\nA multidisciplinary team should be involved in the planning and use of this procedure. The Institute has issued a cancer service guideline on improving outcomes in urological cancers.\n\nFurther research and audit should address quality of life, clinical outcomes and long-term survival.", 'The procedure': "# Indications\n\nTreatment options for prostate cancer depend on whether the disease is localised to the prostate gland. Current management options for localised prostate cancer include radiotherapy, radical prostatectomy and 'watchful waiting'.\n\nRadiation therapy can take the form of external-beam radiotherapy or brachytherapy. Brachytherapy may be given at either low or high dose rates. Low dose rate brachytherapy may be used alone (monotherapy) or in combination with external-beam radiotherapy.\n\n# Outline of the procedure\n\nLow dose brachytherapy is a form of radiotherapy in which radiation is delivered directly to the prostate gland by small radioactive pellets (called seeds).\n\nUnder general or spinal anaesthesia and ultrasound guidance, the seeds are inserted via needles passed through the skin of the perineum. In low dose rate brachytherapy, the seeds are left in place permanently and emit low-dose radiation over several weeks or months.\n\n# Efficacy\n\nThe literature search found no randomised controlled trials that compared low dose rate brachytherapy with other kinds of treatment. Evaluation of the effectiveness of brachytherapy was made difficult by the diversity of the techniques used, the patient selection criteria applied and the different follow-up intervals reported.\n\nA recent large cohort study that compared almost 3000 patients undergoing low dose rate brachytherapy (either as monotherapy or combined with external-beam radiotherapy) with external-beam radiotherapy (> 72 Gy) or radical prostatectomy, found no difference in biochemical-recurrence-free survival between the three treatments at 5 or 7 years follow-up. In a comparative study in which 869 patients were treated with low dose rate brachytherapy, a 0.5 ng/ml PSA nadir level was reached in 86% (748/869) of patients after therapy. No comparison of long-term effects could be made because the outcomes for patients treated with radical prostatectomy were not recorded beyond 2 years.\n\nIn a comparative study involving 1819 patients, overall survival at median follow-up of 58 months in patients with T1 or T2 cancer was found to be similar among those undergoing low dose rate brachytherapy (93%; 679/733 patients), radical prostatectomy (97%; 721/746 patients) and external-beam radiotherapy (96%; 325/340 patients).\n\nIn another study, physical function scores in 92 patients treated with low dose rate brachytherapy and 327 patients treated with radical prostatectomy showed no significant changes from baseline in either group at 24 months. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors considered low dose rate brachytherapy to be an established procedure and stated that the results are comparable with those achieved with surgery or external-beam radiotherapy in well-selected patients.\n\n# Safety\n\nComplications were generally not well reported, but included irritative/obstructive urinary symptoms, rectal symptoms and sexual dysfunction. In one study involving 869 patients undergoing low dose rate brachytherapy, the impotence rate was 10–15%, compared with 45% in 208 patients undergoing radical prostatectomy. The incontinence rate was less than 1% in both groups.\n\nTwo case series included in a Health Technology Assessment Review reported disease-specific quality of life to be lower in patients receiving brachytherapy than in both those receiving external-beam radiotherapy alone and those in a healthy population. However, this review did not differentiate between low dose rate and high dose rate brachytherapy. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted potential complications such as incontinence, infection and erectile dysfunction.\n\n# Other comments\n\nThe data are difficult to interpret because of the other treatment modalities often used alongside this procedure.\n\nIn recommending that further research and audit should address long-term survival, it was noted that men with prostate cancer often die from unrelated causes.\n\nIt was also noted that the appropriate length of long-term follow-up would depend on the stage and grade of the tumour.", 'Further information': "The Institute has issued interventional procedure guidance on laparoscopic radical prostatectomy, high-intensity ultrasound for prostate cancer and cryotherapy for recurrent prostate cancer. It is also preparing guidance on high dose rate brachytherapy [Now published as 'High dose rate brachytherapy in combination with external-beam radiotherapy for localised prostate cancer'].\n\nThe Institute is also developing a clinical guideline: Prostate cancer: diagnosis and treatment [Now published as 'Prostate cancer: diagnosis and treatment'].\n\nAndrew DillonChief ExecutiveJuly 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of low dose rate brachytherapy for localised prostate cancer', January 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Other NICE recommendations on brachytherapy for the treatment of prostate cancer': 'Further recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008, as follows:\n\nBrachytherapy is not recommended for men with high-risk localised prostate cancer.\n\nClinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available.\n\nThe IP guidance on low dose rate brachytherapy for localised prostate cancer remains current, and should be read in conjunction with the clinical guideline.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt has been incorporated into the NICE pathway on prostate cancer, along with other related guidance and products.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg132
39364b6aff40cdcb8c94df5eca70ef072b3ee9e4	nice	Photodynamic therapy for bile duct cancer	Photodynamic therapy for bile duct cancer # Guidance Current evidence on the safety and efficacy of photodynamic therapy (PDT) for bile duct cancer does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake PDT for bile duct cancer should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having PDT for bile duct cancer. Publication of safety and efficacy outcomes will be useful. A randomised trial (PHOTOSTENT 2) is in progress and clinicians are encouraged to enter patients in this trial. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Bile duct cancer may prevent bile flowing from the liver to the intestine. Early cancers are often asymptomatic, but as the disease advances patients may experience symptoms from biliary obstruction, such as jaundice, itchy skin, abdominal discomfort, loss of appetite, loss of weight and fever. PDT is a palliative treatment option for bile duct cancer. Treatment options depend on the stage, size, position and type of tumour. Bile duct cancer is not usually diagnosed before the symptoms of biliary obstruction occur, by which time the cancer may be too advanced for curative surgical resection. Options for palliative treatment include surgical bypass of the bile duct or the insertion of a stent using surgical, endoscopic or percutaneous techniques. The benefits of other palliative treatments such as radiotherapy, chemotherapy and brachytherapy are still being investigated. # Outline of the procedure PDT produces localised tissue necrosis. A photosensitising agent is applied that is absorbed into the tumour tissue. The area is then exposed to laser light of an appropriate wavelength. PDT is usually administered in conjunction with a biliary stenting procedure. The photosensitising agent is injected intravenously and photoactivation is performed approximately 48 hours later. A laser is inserted through a translucent endoscopic catheter situated close to the tumour, or it is placed directly across the tumour. Radiological control is used to ensure correct positioning of the laser fibre. Patients remain in subdued lighting for about 3 days after injection to avoid skin photosensitivity and are then gradually readapted to light. The treatment can be repeated. # Efficacy A randomised controlled study of 39 patients reported that those treated with PDT and biliary stenting had a significantly longer median survival time than patients treated with biliary stenting alone (493 days versus 98 days, p < 0.0001). This study was terminated prematurely because PDT was so superior to stenting alone. Several quality-of-life scores were significantly improved after PDT, including global quality of life, fatigue, itching and weight loss. No significant improvements in quality-of-life scores were reported for the patients receiving biliary stenting alone. A non-randomised study of 44 patients reported that the mean survival after PDT and biliary stenting was 16 months, compared with 12.5 months after biliary stenting alone. For more details, refer to the Sources of evidence. The Specialist Advisors considered that there is not yet enough data to draw clear conclusions about the effect of PDT on survival. One Specialist Advisor stated that this procedure is only effective for tumours that are in visual proximity to the light source. # Safety The most common complications were cholangitis, affecting between 15% (3/20) and 56% (13/23) of patients, and photosensitivity, which was reported in 0% (0/8) to 33% (2/6) of patients. Other reported complications included bilioma, cholecystitis, stenosis and haemobilia. For more details, refer to the Sources of evidence. The Specialist Advisors stated that potential adverse effects of the procedure include cholangitis, photosensitivity, stenosis of the biliary tree, biliary perforation, acute pancreatitis, bleeding and pain. # Other comments It was noted that efficacy may depend on the particular photosensitising agent used. The initial evidence suggests that PDT may be an efficacious palliative technique in patients with bile duct cancer. Andrew DillonChief ExecutiveJuly 2005# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of photodynamic therapy for bile duct cancer', October 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication The guidance was considered for reassessment in July 2008 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of photodynamic therapy (PDT) for bile duct cancer does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake PDT for bile duct cancer should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having PDT for bile duct cancer.\n\nPublication of safety and efficacy outcomes will be useful. A randomised trial (PHOTOSTENT 2) is in progress and clinicians are encouraged to enter patients in this trial. The Institute may review the procedure upon publication of further evidence.", 'The procedure': '# Indications\n\nBile duct cancer may prevent bile flowing from the liver to the intestine. Early cancers are often asymptomatic, but as the disease advances patients may experience symptoms from biliary obstruction, such as jaundice, itchy skin, abdominal discomfort, loss of appetite, loss of weight and fever. PDT is a palliative treatment option for bile duct cancer.\n\nTreatment options depend on the stage, size, position and type of tumour. Bile duct cancer is not usually diagnosed before the symptoms of biliary obstruction occur, by which time the cancer may be too advanced for curative surgical resection. Options for palliative treatment include surgical bypass of the bile duct or the insertion of a stent using surgical, endoscopic or percutaneous techniques. The benefits of other palliative treatments such as radiotherapy, chemotherapy and brachytherapy are still being investigated.\n\n# Outline of the procedure\n\nPDT produces localised tissue necrosis. A photosensitising agent is applied that is absorbed into the tumour tissue. The area is then exposed to laser light of an appropriate wavelength.\n\nPDT is usually administered in conjunction with a biliary stenting procedure. The photosensitising agent is injected intravenously and photoactivation is performed approximately 48 hours later. A laser is inserted through a translucent endoscopic catheter situated close to the tumour, or it is placed directly across the tumour. Radiological control is used to ensure correct positioning of the laser fibre. Patients remain in subdued lighting for about 3 days after injection to avoid skin photosensitivity and are then gradually readapted to light. The treatment can be repeated.\n\n# Efficacy\n\nA randomised controlled study of 39 patients reported that those treated with PDT and biliary stenting had a significantly longer median survival time than patients treated with biliary stenting alone (493 days versus 98 days, p < 0.0001). This study was terminated prematurely because PDT was so superior to stenting alone. Several quality-of-life scores were significantly improved after PDT, including global quality of life, fatigue, itching and weight loss. No significant improvements in quality-of-life scores were reported for the patients receiving biliary stenting alone. A non-randomised study of 44 patients reported that the mean survival after PDT and biliary stenting was 16 months, compared with 12.5 months after biliary stenting alone. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors considered that there is not yet enough data to draw clear conclusions about the effect of PDT on survival. One Specialist Advisor stated that this procedure is only effective for tumours that are in visual proximity to the light source.\n\n# Safety\n\nThe most common complications were cholangitis, affecting between 15% (3/20) and 56% (13/23) of patients, and photosensitivity, which was reported in 0% (0/8) to 33% (2/6) of patients. Other reported complications included bilioma, cholecystitis, stenosis and haemobilia. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that potential adverse effects of the procedure include cholangitis, photosensitivity, stenosis of the biliary tree, biliary perforation, acute pancreatitis, bleeding and pain.\n\n# Other comments\n\nIt was noted that efficacy may depend on the particular photosensitising agent used.\n\nThe initial evidence suggests that PDT may be an efficacious palliative technique in patients with bile duct cancer.\n\nAndrew DillonChief ExecutiveJuly 2005', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of photodynamic therapy for bile duct cancer', October 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': 'The guidance was considered for reassessment in July 2008 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg134
d1191e5783def39c4e9b45c8b2b01c388286fcbe	nice	Laparoscopic liver resection	Laparoscopic liver resection # Guidance Current evidence on the safety and efficacy of laparoscopic liver resection appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. Patient selection for laparoscopic liver resection should be carried out by a multidisciplinary team. Surgeons undertaking laparoscopic liver resection should have specialist training and expertise both in laparoscopic techniques and in the specific issues relating to liver surgery.# The procedure # Indications A common indication for laparoscopic liver resection is a solitary liver metastasis from colorectal cancer, but it may also be used for hepatocellular carcinoma (HCC) and for benign liver tumours or cysts. The early stages of primary and secondary liver cancer are often asymptomatic. As the tumour grows, symptoms may include jaundice, loss of appetite, loss of weight, nausea and tiredness. Benign liver tumours are usually small and asymptomatic, but if they become large they may cause symptoms such as pain, nausea and vomiting. Open surgical resection is the standard treatment for patients with localised colorectal metastases of the liver or HCC. A number of alternative therapies have also been developed, including hepatic artery infusion chemotherapy, percutaneous ethanol injection, cryoablation, microwave coagulation therapy, laser-induced thermotherapy and radiofrequency ablation. Benign liver tumours are usually treated only if they are causing symptoms; the standard treatment is open surgical resection. # Outline of the procedure Laparoscopic liver resection is performed under general anaesthesia. The abdomen is insufflated with carbon dioxide and a number of small incisions are made to provide access for the laparoscope and surgical instruments. Diathermy is used to mark the line of transection on the liver surface. The hepatic parenchyma is then transected and the main blood vessels and bile ducts are divided and closed with clips or staples. The resected liver is enclosed in a bag and removed through a small incision in the umbilical area. Haemostasis of the transection line may be obtained by several techniques including cautery, haemostatic swabs and fibrin glue. Hand-assisted laparoscopic liver resection allows the surgeon to place one hand in the abdomen while maintaining the pneumoperitoneum required for laparoscopy. An additional small incision is made which is just large enough for the surgeon's hand, and an airtight 'sleeve' device is used to form a seal around the incision. # Efficacy One study of 55 patients reported that there was no difference in the overall patient survival rate or disease-free survival rate between laparoscopic liver resection and open resection. In five studies (n = 217) that compared laparoscopic liver resection with open resection in patients with malignant tumours, there were no statistically significant differences in the extent of the resection margins. Four of six non-randomised comparative studies reported that the postoperative hospital stay was significantly shorter after laparoscopic liver resection (mean stay ranged from 4 to 15 days) than after open liver resection (mean stay ranged from 8 to 22 days). For more details, refer to the Sources of evidence. The Specialist Advisors noted that there were concerns that resection margins may be compromised which may put the patient at risk of increased local tumour recurrence. # Safety All of the studies reported the rate of conversion to laparotomy, which ranged from 0% (0/30) to 15% (2/13). Five of seven studies reported that blood transfusion was necessary during laparoscopic surgery in 0% (0/18) to 13% (4/30) of patients. Complications included chest infection in 15% (2/13), liver failure in 8% (1/13), ascites in 8% (1/13), atelectasis of the left lower pulmonary lobe in 8% (1/13) and biliary leak in 5% (1/21) of patients. For more details, refer to the Sources of evidence. The Specialist Advisors stated that potential adverse effects included death due to uncontrollable haemorrhage, bile leakage, gas embolism, deep vein thrombosis and infection.# Further information The Institute has issued guidance on radiofrequency ablation of hepatocellular carcinoma, radiofrequency ablation for the treatment of colorectal metastases in the liver and selective internal radiation therapy for colorectal metastases in the liver. The Institute has also published a cancer service guideline on improving outcomes in colorectal cancers. Andrew DillonChief ExecutiveJuly 2005 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of laparoscopic liver resection', January 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It has been incorporated into the NICE pathway on colorectal cancer, along with other related guidance and products. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of laparoscopic liver resection appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nPatient selection for laparoscopic liver resection should be carried out by a multidisciplinary team. Surgeons undertaking laparoscopic liver resection should have specialist training and expertise both in laparoscopic techniques and in the specific issues relating to liver surgery.', 'The procedure': "# Indications\n\nA common indication for laparoscopic liver resection is a solitary liver metastasis from colorectal cancer, but it may also be used for hepatocellular carcinoma (HCC) and for benign liver tumours or cysts.\n\nThe early stages of primary and secondary liver cancer are often asymptomatic. As the tumour grows, symptoms may include jaundice, loss of appetite, loss of weight, nausea and tiredness. Benign liver tumours are usually small and asymptomatic, but if they become large they may cause symptoms such as pain, nausea and vomiting.\n\nOpen surgical resection is the standard treatment for patients with localised colorectal metastases of the liver or HCC. A number of alternative therapies have also been developed, including hepatic artery infusion chemotherapy, percutaneous ethanol injection, cryoablation, microwave coagulation therapy, laser-induced thermotherapy and radiofrequency ablation. Benign liver tumours are usually treated only if they are causing symptoms; the standard treatment is open surgical resection.\n\n# Outline of the procedure\n\nLaparoscopic liver resection is performed under general anaesthesia. The abdomen is insufflated with carbon dioxide and a number of small incisions are made to provide access for the laparoscope and surgical instruments. Diathermy is used to mark the line of transection on the liver surface. The hepatic parenchyma is then transected and the main blood vessels and bile ducts are divided and closed with clips or staples. The resected liver is enclosed in a bag and removed through a small incision in the umbilical area. Haemostasis of the transection line may be obtained by several techniques including cautery, haemostatic swabs and fibrin glue.\n\nHand-assisted laparoscopic liver resection allows the surgeon to place one hand in the abdomen while maintaining the pneumoperitoneum required for laparoscopy. An additional small incision is made which is just large enough for the surgeon's hand, and an airtight 'sleeve' device is used to form a seal around the incision.\n\n# Efficacy\n\nOne study of 55 patients reported that there was no difference in the overall patient survival rate or disease-free survival rate between laparoscopic liver resection and open resection. In five studies (n = 217) that compared laparoscopic liver resection with open resection in patients with malignant tumours, there were no statistically significant differences in the extent of the resection margins.\n\nFour of six non-randomised comparative studies reported that the postoperative hospital stay was significantly shorter after laparoscopic liver resection (mean stay ranged from 4 to 15 days) than after open liver resection (mean stay ranged from 8 to 22 days). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that there were concerns that resection margins may be compromised which may put the patient at risk of increased local tumour recurrence.\n\n# Safety\n\nAll of the studies reported the rate of conversion to laparotomy, which ranged from 0% (0/30) to 15% (2/13). Five of seven studies reported that blood transfusion was necessary during laparoscopic surgery in 0% (0/18) to 13% (4/30) of patients. Complications included chest infection in 15% (2/13), liver failure in 8% (1/13), ascites in 8% (1/13), atelectasis of the left lower pulmonary lobe in 8% (1/13) and biliary leak in 5% (1/21) of patients. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that potential adverse effects included death due to uncontrollable haemorrhage, bile leakage, gas embolism, deep vein thrombosis and infection.", 'Further information': "The Institute has issued guidance on radiofrequency ablation of hepatocellular carcinoma, radiofrequency ablation for the treatment of colorectal metastases in the liver and selective internal radiation therapy for colorectal metastases in the liver. The Institute has also published a cancer service guideline on improving outcomes in colorectal cancers.\n\nAndrew DillonChief ExecutiveJuly 2005\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of laparoscopic liver resection', January 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt has been incorporated into the NICE pathway on colorectal cancer, along with other related guidance and products.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2005. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg135
8fc150c2067edaf4a0faf40d87beec0528274477	nice	Collagen injection for vocal cord augmentation	Collagen injection for vocal cord augmentation # Guidance Current evidence on collagen injection for vocal cord augmentation suggests that there are no major safety concerns and that it is efficacious in patients requiring short-term symptom relief. However, evidence on long-term efficacy is lacking. Patients should be fully informed of the uncertainty about the procedure's long-term efficacy, and of the alternative treatment options. Use of NICE's information for the public is recommended.# The procedure # Indications Glottic insufficiency, which may be secondary to vocal fold (cord) scarring, atrophy or paralysis, is a condition that leaves patients with phonatory compromise in both voice intensity and frequency. Vocal fold paresis (where the nerves that control the muscles acting on the vocal fold fail) may be idiopathic or have an iatrogenic cause; one or both of the vocal folds may be affected. Conservative management by voice therapy may be beneficial if the muscle groups affected by vocal fold paresis can be developed through vocal exercise. Surgical approaches can be used to reposition or reshape the vocal fold and they may involve implanting a physical device. Autogenous fat, Teflon, silicone or collagen can be injected to improve vocal fold function. Of these, autogenous fat is generally well tolerated. Teflon and silicone, however, may (rarely) produce complications because of sensitivity reactions to the materials used. # Outline of the procedure The collagen is injected either transorally or transcutaneously from below the vocal fold using a laryngeal needle. The exact placement of collagen varies depending on the pathology of the condition. The procedure can be carried out with local anaesthesia, and may not require admission. A variety of collagen products have been used in research studies, such as biochemically cross-linked products and purified bovine collagen. Patients who are selected for therapy commonly undergo a skin sensitivity test. Antibiotic prophylaxis may be given. # Efficacy In a case series of 45 patients with glottic insufficiency for whom other forms of treatment were considered unsuitable, collagen injection improved the maximum voice intensity by a mean of 2.91 dB (p < 0.026) at 12 months after the procedure. However, the mean change in normal voice intensity was not statistically significant. In 27 patients with vocal fold paralysis or glottic insufficiency following laryngeal surgery, voice intensity and phonation time were found to have improved significantly following collagen injection. All 27 patients reported an improvement in at least one subjective voice assessment parameter up to 16 weeks after the collagen injection. In one case series of 18 patients with electromyographically confirmed vocal fold paralysis, 93% (13/14) of patients who were injected with purified bovine collagen showed good improvement in dysphonia score compared with baseline at 6.5 months after treatment. In the same study, an improvement was found in maximum phonation time (8.6 seconds compared with 5.7 seconds at baseline). In a longer-term follow-up of patients in this study, 83% (5/6) of patients maintained good results in terms of subjective voice assessment at 3 years. In the four patients available for objective voice assessment at 3 years, maximum phonation time had improved further (12.2 seconds compared with 4.2 seconds at baseline). For more details, refer to the Sources of evidence. The Specialist Advisors noted that injected collagen may be absorbed over time and may require replacement in the long term. # Safety In a case series of 27 patients treated with collagen injection, one patient had an immediate short-term decrease in voice quality, which was associated with excessive injection, and one patient had transient vocal fold oedema. Two case series with a total of 63 patients reported no serious adverse events up to 12 months following the procedure. In six patients followed-up for 3 years, there were no complications such as seroma, granuloma formation or migration of injected collagen. For more details, refer to the Sources of evidence. The Specialist Advisors noted that transmission of variant Creutzfeldt–Jakob disease and allergic reactions are theoretical safety concerns with the use of bovine collagen. # Other comments It was noted that collagen was just one of a variety of agents used for vocal cord augmentation, and that these may have different risk and benefit profiles. Surgery may be preferable for patients who require long-term improvement in phonation. The evidence is limited, but it was considered sufficient to support use of the procedure as palliative treatment in patients with limited life-expectancy.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedure overview of collagen injection for vocal cord augmentation, December 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on collagen injection for vocal cord augmentation suggests that there are no major safety concerns and that it is efficacious in patients requiring short-term symptom relief. However, evidence on long-term efficacy is lacking.\n\nPatients should be fully informed of the uncertainty about the procedure's long-term efficacy, and of the alternative treatment options. Use of NICE's information for the public is recommended.", 'The procedure': '# Indications\n\nGlottic insufficiency, which may be secondary to vocal fold (cord) scarring, atrophy or paralysis, is a condition that leaves patients with phonatory compromise in both voice intensity and frequency. Vocal fold paresis (where the nerves that control the muscles acting on the vocal fold fail) may be idiopathic or have an iatrogenic cause; one or both of the vocal folds may be affected.\n\nConservative management by voice therapy may be beneficial if the muscle groups affected by vocal fold paresis can be developed through vocal exercise. Surgical approaches can be used to reposition or reshape the vocal fold and they may involve implanting a physical device. Autogenous fat, Teflon, silicone or collagen can be injected to improve vocal fold function. Of these, autogenous fat is generally well tolerated. Teflon and silicone, however, may (rarely) produce complications because of sensitivity reactions to the materials used.\n\n# Outline of the procedure\n\nThe collagen is injected either transorally or transcutaneously from below the vocal fold using a laryngeal needle. The exact placement of collagen varies depending on the pathology of the condition. The procedure can be carried out with local anaesthesia, and may not require admission. A variety of collagen products have been used in research studies, such as biochemically cross-linked products and purified bovine collagen. Patients who are selected for therapy commonly undergo a skin sensitivity test. Antibiotic prophylaxis may be given.\n\n# Efficacy\n\nIn a case series of 45 patients with glottic insufficiency for whom other forms of treatment were considered unsuitable, collagen injection improved the maximum voice intensity by a mean of 2.91 dB (p < 0.026) at 12 months after the procedure. However, the mean change in normal voice intensity was not statistically significant.\n\nIn 27 patients with vocal fold paralysis or glottic insufficiency following laryngeal surgery, voice intensity and phonation time were found to have improved significantly following collagen injection. All 27 patients reported an improvement in at least one subjective voice assessment parameter up to 16 weeks after the collagen injection.\n\nIn one case series of 18 patients with electromyographically confirmed vocal fold paralysis, 93% (13/14) of patients who were injected with purified bovine collagen showed good improvement in dysphonia score compared with baseline at 6.5 months after treatment. In the same study, an improvement was found in maximum phonation time (8.6 seconds compared with 5.7 seconds at baseline). In a longer-term follow-up of patients in this study, 83% (5/6) of patients maintained good results in terms of subjective voice assessment at 3 years. In the four patients available for objective voice assessment at 3 years, maximum phonation time had improved further (12.2 seconds compared with 4.2 seconds at baseline). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that injected collagen may be absorbed over time and may require replacement in the long term.\n\n# Safety\n\nIn a case series of 27 patients treated with collagen injection, one patient had an immediate short-term decrease in voice quality, which was associated with excessive injection, and one patient had transient vocal fold oedema.\n\nTwo case series with a total of 63 patients reported no serious adverse events up to 12 months following the procedure. In six patients followed-up for 3 years, there were no complications such as seroma, granuloma formation or migration of injected collagen. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that transmission of variant Creutzfeldt–Jakob disease and allergic reactions are theoretical safety concerns with the use of bovine collagen.\n\n# Other comments\n\nIt was noted that collagen was just one of a variety of agents used for vocal cord augmentation, and that these may have different risk and benefit profiles.\n\nSurgery may be preferable for patients who require long-term improvement in phonation.\n\nThe evidence is limited, but it was considered sufficient to support use of the procedure as palliative treatment in patients with limited life-expectancy.', 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedure overview of collagen injection for vocal cord augmentation, December 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg130
4e62c4e35c44ff323c222e409ab31c7213df61d1	nice	Interstitial laser therapy for fibroadenomas of the breast	Interstitial laser therapy for fibroadenomas of the breast # Guidance Current evidence on the safety and efficacy of interstitial laser therapy for fibroadenomas of the breast does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake interstitial laser therapy for fibroadenomas of the breast should take the following actions. Inform the clinical governance leads in their Trusts. Audit and review all patients having interstitial laser therapy for fibroadenomas of the breast. Ensure that patients understand the benign nature of fibroadenomas, and that watchful waiting is an option. Patients should be provided with clear written information and use of NICE's information for the public is recommended. This procedure should be carried out only within specialist breast services. Publication of safety and efficacy outcomes will be useful. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications A fibroadenoma is a benign solid lump of breast tissue, which is thought to result from an increased sensitivity to oestrogen. Fibroadenomas are very common and it is not unusual to have more than one. They are mostly found in young women but can occur in women of any age. Most fibroadenomas do not enlarge after diagnosis. Some get smaller and some eventually disappear over time. These recommendations relate to options for breast fibroadenomas that do not resolve. Once the diagnosis has been confirmed, conservative management is often agreed, with clinical review only. If the fibroadenoma persists or grows, or if the patient is anxious for it to be removed, it can be excised by a small open operation using general anaesthesia. Interstitial laser therapy is an alternative to open surgery. # Outline of the procedure High-energy light delivered via a laser fibre is used to destroy the fibroadenoma. The fibre is positioned through a needle inserted percutaneously under local anaesthesia. The tip of the needle is positioned at the centre of the lump under ultrasound guidance. Laser energy is delivered through a pre-sterilised bare fibre passed through the needle a short distance beyond the tip. The energy is delivered in continuous wave mode for a few minutes. For larger lumps, multiple needles are inserted 1 cm apart, with a laser fibre through each. There may be lower rates of infection with interstitial laser therapy compared with open surgery, and a more acceptable aesthetic result. # Efficacy In a case series of 24 patients, interstitial laser therapy reduced fibroadenoma size (as assessed by ultrasound measurement) from a mean length of 25 mm at baseline to 14 mm at 3 months, 10 mm at 6 months, and 0 mm at 12 months. There were no palpable fibroadenomas in the 14 women followed-up for 12 months. In another case series, the mean volume of the fibroadenomas in 27 women was significantly smaller 8 weeks after the procedure (0.68 cm3 compared with 2.17 cm3 at baseline; p < 0.001). Clinical assessment also demonstrated a significant decrease in area following interstitial laser therapy (a mean of 1.25 cm2 compared with 2.60 cm2 at baseline; p < 0.001). However, at 8 weeks 37% (10/27) of women had a residual lump with a diameter of more than 1 cm. For more details, refer to the Sources of evidence. The Specialist Advisors noted that the lack of material for biopsy with this procedure (in contrast to surgical excision) means that the benign diagnosis cannot be confirmed. # Safety In a case series of 24 women who had undergone interstitial laser therapy, 83% (20/24) reported some discomfort during the procedure. Severe pain in 17% (4/24) of women led to the treatment being stopped prematurely. In this case series and another that involved 27 women, local tenderness that lasted from 1 to 8 weeks was reported in all of the women. In one of the case series, 30% (8/27) of women had skin blanching at the needle site after 80–100 seconds of the treatment, and these women later developed epithelial breakdown and hyperpigmentation in the same area (follow-up 8 weeks). In the second case series, 17% (4/24) of women had bruising that resolved within 1 week. For more details, refer to the Sources of evidence. The Specialist Advisors noted that the reported adverse events include local burns at the needle site, and that the theoretical complications include local infection, and bleeding if the needle strikes a blood vessel. # Other comments It was noted that there are variations in the technique that have potentially different efficacy profiles.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedure overview of interstitial laser therapy for fibroadenomas of the breast, December 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of interstitial laser therapy for fibroadenomas of the breast does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake interstitial laser therapy for fibroadenomas of the breast should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nAudit and review all patients having interstitial laser therapy for fibroadenomas of the breast.\n\nEnsure that patients understand the benign nature of fibroadenomas, and that watchful waiting is an option. Patients should be provided with clear written information and use of NICE's information for the public is recommended.\n\nThis procedure should be carried out only within specialist breast services.\n\nPublication of safety and efficacy outcomes will be useful. The Institute may review the procedure upon publication of further evidence.", 'The procedure': '# Indications\n\nA fibroadenoma is a benign solid lump of breast tissue, which is thought to result from an increased sensitivity to oestrogen. Fibroadenomas are very common and it is not unusual to have more than one. They are mostly found in young women but can occur in women of any age.\n\nMost fibroadenomas do not enlarge after diagnosis. Some get smaller and some eventually disappear over time. These recommendations relate to options for breast fibroadenomas that do not resolve.\n\nOnce the diagnosis has been confirmed, conservative management is often agreed, with clinical review only. If the fibroadenoma persists or grows, or if the patient is anxious for it to be removed, it can be excised by a small open operation using general anaesthesia. Interstitial laser therapy is an alternative to open surgery.\n\n# Outline of the procedure\n\nHigh-energy light delivered via a laser fibre is used to destroy the fibroadenoma. The fibre is positioned through a needle inserted percutaneously under local anaesthesia. The tip of the needle is positioned at the centre of the lump under ultrasound guidance. Laser energy is delivered through a pre-sterilised bare fibre passed through the needle a short distance beyond the tip. The energy is delivered in continuous wave mode for a few minutes. For larger lumps, multiple needles are inserted 1 cm apart, with a laser fibre through each.\n\nThere may be lower rates of infection with interstitial laser therapy compared with open surgery, and a more acceptable aesthetic result.\n\n# Efficacy\n\nIn a case series of 24 patients, interstitial laser therapy reduced fibroadenoma size (as assessed by ultrasound measurement) from a mean length of 25 mm at baseline to 14 mm at 3 months, 10 mm at 6 months, and 0 mm at 12 months. There were no palpable fibroadenomas in the 14 women followed-up for 12 months.\n\nIn another case series, the mean volume of the fibroadenomas in 27 women was significantly smaller 8 weeks after the procedure (0.68 cm3 compared with 2.17 cm3 at baseline; p < 0.001). Clinical assessment also demonstrated a significant decrease in area following interstitial laser therapy (a mean of 1.25 cm2 compared with 2.60 cm2 at baseline; p < 0.001). However, at 8 weeks 37% (10/27) of women had a residual lump with a diameter of more than 1 cm. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that the lack of material for biopsy with this procedure (in contrast to surgical excision) means that the benign diagnosis cannot be confirmed.\n\n# Safety\n\nIn a case series of 24 women who had undergone interstitial laser therapy, 83% (20/24) reported some discomfort during the procedure. Severe pain in 17% (4/24) of women led to the treatment being stopped prematurely. In this case series and another that involved 27 women, local tenderness that lasted from 1 to 8 weeks was reported in all of the women.\n\nIn one of the case series, 30% (8/27) of women had skin blanching at the needle site after 80–100 seconds of the treatment, and these women later developed epithelial breakdown and hyperpigmentation in the same area (follow-up 8 weeks). In the second case series, 17% (4/24) of women had bruising that resolved within 1 week. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that the reported adverse events include local burns at the needle site, and that the theoretical complications include local infection, and bleeding if the needle strikes a blood vessel.\n\n# Other comments\n\nIt was noted that there are variations in the technique that have potentially different efficacy profiles.', 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedure overview of interstitial laser therapy for fibroadenomas of the breast, December 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg131
0e5dadfadbee24dd0a89d191cc30708fe968cee5	nice	Leukapheresis for inflammatory bowel disease	Leukapheresis for inflammatory bowel disease # Guidance Current evidence suggests that there are no major safety concerns for the use of leukapheresis for inflammatory bowel disease. Leukapheresis may be beneficial in carefully selected patients with ulcerative colitis, but the evidence on efficacy is not yet adequate to support its use in these patients without special arrangements for consent and for audit or research as set out in 1.4. There is inadequate evidence to draw any conclusions about the efficacy of leukapheresis in patients with Crohn's disease and it should only be used in accordance with special arrangements for consent and audit as set out in 1.4. Clinicians wishing to undertake leukapheresis for inflammatory bowel disease should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's efficacy and provide them with clear written information. Use of NICE's information for the public is recommended. Audit and review clinical outcomes of all patients having leukapheresis. Publication of current and future research studies will be useful. NICE may review the procedure upon publication of further evidence.# The procedure # Indications Ulcerative colitis and Crohn's disease are the most common forms of inflammatory bowel disease. Ulcerative colitis causes inflammation and ulceration of the rectum and colon. Symptoms include bloody diarrhoea and rectal bleeding. Crohn's disease usually causes inflammation and ulceration of the small intestine, but it can affect any part of the digestive tract. The main symptoms are abdominal pain, diarrhoea and weight loss. Both ulcerative colitis and Crohn's disease are chronic conditions characterised by periods of clinical relapse and remission. Conservative treatments include dietary measures and medication to control inflammation, which may include immunosuppressants. Patients with ulcerative colitis that does not respond to medical therapy may be treated with surgery to remove the colon. Although surgery may also be used for patients with Crohn's disease, it may not be curative and the disease often recurs in a different part of the digestive tract. # Outline of the procedure Leukapheresis involves extracorporeal removal of leukocytes from the blood, either by centrifugation or through an adsorptive system. In each system, venous blood is removed in a continuous flow, anticoagulated, processed to deplete the leukocytes and returned to the circulation. Different apheresis systems remove different populations of white blood cells. Leukapheresis using centrifugation removes a proportion of neutrophils and lymphocytes. Filter columns, which may contain cellulose acetate beads or a polyester fibre filter, remove a large proportion of granulocytes and monocytes and some also remove lymphocytes. The exact mode of action of these procedures is unknown. # Efficacy In one randomised controlled trial of patients with ulcerative colitis, 74% (29/39) of patients treated with leukapheresis had an 'excellent' or 'moderate' improvement in symptoms, compared with 38% (14/37) of patients treated with high-dose steroids (p = 0.005). In four case series, 54% (24/44) to 82% (32/39) of patients with ulcerative colitis had an initial remission of disease after treatment. In one study, the proportion of patients in clinical remission dropped from 82% (32/39) at 12 weeks to 67% (26/39) at 12 months after the final treatment. In two further studies, 30% (10/33) and 39% (13/33) of patients relapsed during maintenance therapy after initial complete remission. In a small randomised controlled trial of patients with Crohn's disease, 100% (12/12) of patients treated with leukapheresis were successfully withdrawn from steroid therapy, compared with 67% (10/15) of patients who were not treated with leukapheresis (p = 0.074). There was no significant difference between the two groups in disease recurrence at 18-month follow-up. For more details, refer to the Sources of evidence. The Specialist Advisors stated that some uncertainty remained about the efficacy of leukapheresis for inflammatory bowel disease because data from randomised controlled trials were insufficient. # Safety Most studies reported only mild adverse events such as dizziness, light headedness, headache and flushing. In three case series, the proportion of patients experiencing at least one non-severe adverse event ranged from 9% (5/53) to 18% (7/39). In a randomised controlled trial, the incidence of adverse events was significantly lower in the group treated with leukapheresis than in the group treated with high-dose steroids (24% versus 47%, p < 0.001). In the same trial, adverse events were described as moderate or severe in 12% (5/42) of patients treated with leukapheresis: one patient had toxic shock, one patient had chest pain, one patient had anaemia and two patients had a headache. For more details, refer to the Sources of evidence. The Specialist Advisors stated that potential adverse events included infection, headache, palpitations, nausea, vomiting, fever, chills, respiratory distress and chest discomfort. # Other comments It was noted that leukapheresis is an established technique for other conditions. It was also noted that there are different techniques for leukapheresis, and these may have different risk and benefit profiles.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedures overview of leukapheresis for inflammatory bowel disease, August 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence suggests that there are no major safety concerns for the use of leukapheresis for inflammatory bowel disease.\n\nLeukapheresis may be beneficial in carefully selected patients with ulcerative colitis, but the evidence on efficacy is not yet adequate to support its use in these patients without special arrangements for consent and for audit or research as set out in 1.4.\n\nThere is inadequate evidence to draw any conclusions about the efficacy of leukapheresis in patients with Crohn's disease and it should only be used in accordance with special arrangements for consent and audit as set out in 1.4.\n\nClinicians wishing to undertake leukapheresis for inflammatory bowel disease should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's efficacy and provide them with clear written information. Use of NICE's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having leukapheresis.\n\nPublication of current and future research studies will be useful. NICE may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nUlcerative colitis and Crohn's disease are the most common forms of inflammatory bowel disease. Ulcerative colitis causes inflammation and ulceration of the rectum and colon. Symptoms include bloody diarrhoea and rectal bleeding. Crohn's disease usually causes inflammation and ulceration of the small intestine, but it can affect any part of the digestive tract. The main symptoms are abdominal pain, diarrhoea and weight loss. Both ulcerative colitis and Crohn's disease are chronic conditions characterised by periods of clinical relapse and remission.\n\nConservative treatments include dietary measures and medication to control inflammation, which may include immunosuppressants. Patients with ulcerative colitis that does not respond to medical therapy may be treated with surgery to remove the colon. Although surgery may also be used for patients with Crohn's disease, it may not be curative and the disease often recurs in a different part of the digestive tract.\n\n# Outline of the procedure\n\nLeukapheresis involves extracorporeal removal of leukocytes from the blood, either by centrifugation or through an adsorptive system. In each system, venous blood is removed in a continuous flow, anticoagulated, processed to deplete the leukocytes and returned to the circulation.\n\nDifferent apheresis systems remove different populations of white blood cells. Leukapheresis using centrifugation removes a proportion of neutrophils and lymphocytes. Filter columns, which may contain cellulose acetate beads or a polyester fibre filter, remove a large proportion of granulocytes and monocytes and some also remove lymphocytes. The exact mode of action of these procedures is unknown.\n\n# Efficacy\n\nIn one randomised controlled trial of patients with ulcerative colitis, 74% (29/39) of patients treated with leukapheresis had an 'excellent' or 'moderate' improvement in symptoms, compared with 38% (14/37) of patients treated with high-dose steroids (p = 0.005).\n\nIn four case series, 54% (24/44) to 82% (32/39) of patients with ulcerative colitis had an initial remission of disease after treatment. In one study, the proportion of patients in clinical remission dropped from 82% (32/39) at 12 weeks to 67% (26/39) at 12 months after the final treatment. In two further studies, 30% (10/33) and 39% (13/33) of patients relapsed during maintenance therapy after initial complete remission.\n\nIn a small randomised controlled trial of patients with Crohn's disease, 100% (12/12) of patients treated with leukapheresis were successfully withdrawn from steroid therapy, compared with 67% (10/15) of patients who were not treated with leukapheresis (p = 0.074). There was no significant difference between the two groups in disease recurrence at 18-month follow-up. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that some uncertainty remained about the efficacy of leukapheresis for inflammatory bowel disease because data from randomised controlled trials were insufficient.\n\n# Safety\n\nMost studies reported only mild adverse events such as dizziness, light headedness, headache and flushing. In three case series, the proportion of patients experiencing at least one non-severe adverse event ranged from 9% (5/53) to 18% (7/39).\n\nIn a randomised controlled trial, the incidence of adverse events was significantly lower in the group treated with leukapheresis than in the group treated with high-dose steroids (24% versus 47%, p < 0.001). In the same trial, adverse events were described as moderate or severe in 12% (5/42) of patients treated with leukapheresis: one patient had toxic shock, one patient had chest pain, one patient had anaemia and two patients had a headache. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors stated that potential adverse events included infection, headache, palpitations, nausea, vomiting, fever, chills, respiratory distress and chest discomfort.\n\n# Other comments\n\nIt was noted that leukapheresis is an established technique for other conditions.\n\nIt was also noted that there are different techniques for leukapheresis, and these may have different risk and benefit profiles.", 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedures overview of leukapheresis for inflammatory bowel disease, August 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg126
62ab89c8555e2d3e1eb1408190324305b5c85e63	nice	Totally endoscopic robotically assisted coronary artery bypass grafting	Totally endoscopic robotically assisted coronary artery bypass grafting Evidence-based recommendations on totally endoscopic robotically assisted coronary artery bypass grafting (TECAB). This involves keyhole surgery using small, remote-controlled robotic arms to carry out the grafting procedure. # Guidance Current evidence on the safety and efficacy of totally endoscopic robotically assisted coronary artery bypass grafting does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake totally endoscopic robotically assisted coronary artery bypass grafting should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of NICE's information for the public is recommended. Enter all patients having totally endoscopic robotically assisted coronary artery bypass grafting onto the National Congenital Heart Disease Audit Database managed by the National Institute for Cardiovascular Outcomes Research. Contact bartshealth.nicor-generalenquiries@nhs.net for details. Publication of safety and efficacy outcomes will be useful. NICE may review the procedure upon publication of further evidence.# The procedure # Indications In coronary artery disease, plaque deposits on the inner walls of the coronary arteries lead to narrowing or occlusion, and subsequently decreased oxygen supply to the heart. This may cause angina or myocardial infarction, and long-term weakening of the heart muscle leading to heart failure or arrhythmia. The aim of a coronary artery bypass graft (CABG) is to increase the flow of blood to the heart by inserting grafts to bypass narrowed or obstructed coronary arteries. CABG is usually performed with open surgery through a sternotomy. Less invasive approaches avoiding sternotomy, cardiopulmonary bypass and general anaesthesia have been developed, using either left anterior small thoracotomy (LAST), regional anaesthesia or catheter-based intervention. # Outline of the procedure Totally endoscopic robotically assisted coronary artery bypass (TECAB) systems vary, but they generally include a surgeon's viewing and control console with display system. Remote-control handles control robotic arms that position and precisely manoeuvre an endoscope and endoscopic instruments within the patient. Some equipment uses voice-controlled robotic arms. Following deflation of the lung, small port incisions are made in three intercostal spaces through which one robotic arm carrying the endoscope and two arms with surgical implement attachments are introduced. Grafts are harvested from suitable donor sites, and are used to bypass one or more diseased coronary arteries. TECAB treatment of the beating heart is carried out using a stabilisation device consisting of two branches that immobilise the site for anastomosis while the heart continues to beat. This removes the need for cardiopulmonary bypass. The stabilisation device is introduced into the chest through an additional port incision. # Efficacy Fully patent grafts were achieved in 95% (21/22) of patients when assessed at 3 months by postoperative angiography, together with good functional results. Most case series used duration of operation as a measure and this varied according to the type of procedure undertaken and the number of vessels bypassed. In 45 consecutive patients undergoing TECAB, the mean operating time was 4 hours 12 minutes for single vessel surgery and 6 hours 18 minutes for multiple vessel surgery. In 35 patients, including eight in whom the procedure was performed on the beating heart, the operating time ranged from 3 hours 30 minutes to 8 hours (mean 5 hours 47 minutes). In a further 37 patients (29 of whom had the beating heart procedure), the mean operating time for the early cases in the series was 4 hours 40 minutes, but this was reduced to 3 hours 6 minutes following the introduction of endoscopic stabilisation. The mean length of stay in an intensive care unit varied from 14 hours to 74 hours, and the mean total length of hospital stay ranged from 5.0 to 15.4 days. The upper limits for length of stay were following multiple vessel surgery. For more details, refer to the Sources of evidence. The Specialist Advisors noted that bleeding could potentially make vessel identification difficult. They also noted that patency rates of coronary bypass grafts were not sufficiently well documented. # Safety Conversion rates to open procedures (either mini-thoracotomy or full sternotomy) were reported in all case series and ranged from 19% (5/27) to 51% (19/37) of procedures initiated as TECAB. There were no cases of operative mortality associated with the TECAB procedure (n = 142). In a case series of 45 patients, operative complications included port access failure in 7% (3/45) of patients, prolonged cross clamp time in 9% (4/45), myocardial infarction in 2% (1/45), hypoxic brain damage in 2% (1/45) and internal thoracic artery injury in 2% (1/45) of patients. In a series of 45 patients, 4% (2/45) needed secondary intervention because of bleeding from the site of anastomosis. There were no cases of wound infection at the port site throughout the series. For more details, refer to the Sources of evidence. The Specialist Advisors noted theoretical complications as myocardial infarction, pneumothorax, cardiac tamponade and fatal haemorrhage. They also noted that there is potential for stenosis or occlusion at the site of anastomosis. # Other comments There are a number of other procedures for treating patients with coronary artery disease but no good studies have been found that compare these with TECAB.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedures overview of totally endoscopic robotically assisted coronary artery bypass surgery, November 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind. ISBN: 978-1-4731-4017-2	{'Guidance': "Current evidence on the safety and efficacy of totally endoscopic robotically assisted coronary artery bypass grafting does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake totally endoscopic robotically assisted coronary artery bypass grafting should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of NICE's information for the public is recommended.\n\nEnter all patients having totally endoscopic robotically assisted coronary artery bypass grafting onto the National Congenital Heart Disease Audit Database managed by the National Institute for Cardiovascular Outcomes Research. Contact bartshealth.nicor-generalenquiries@nhs.net for details.\n\nPublication of safety and efficacy outcomes will be useful. NICE may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nIn coronary artery disease, plaque deposits on the inner walls of the coronary arteries lead to narrowing or occlusion, and subsequently decreased oxygen supply to the heart. This may cause angina or myocardial infarction, and long-term weakening of the heart muscle leading to heart failure or arrhythmia.\n\nThe aim of a coronary artery bypass graft (CABG) is to increase the flow of blood to the heart by inserting grafts to bypass narrowed or obstructed coronary arteries.\n\nCABG is usually performed with open surgery through a sternotomy. Less invasive approaches avoiding sternotomy, cardiopulmonary bypass and general anaesthesia have been developed, using either left anterior small thoracotomy (LAST), regional anaesthesia or catheter-based intervention.\n\n# Outline of the procedure\n\nTotally endoscopic robotically assisted coronary artery bypass (TECAB) systems vary, but they generally include a surgeon's viewing and control console with display system. Remote-control handles control robotic arms that position and precisely manoeuvre an endoscope and endoscopic instruments within the patient. Some equipment uses voice-controlled robotic arms.\n\nFollowing deflation of the lung, small port incisions are made in three intercostal spaces through which one robotic arm carrying the endoscope and two arms with surgical implement attachments are introduced. Grafts are harvested from suitable donor sites, and are used to bypass one or more diseased coronary arteries.\n\nTECAB treatment of the beating heart is carried out using a stabilisation device consisting of two branches that immobilise the site for anastomosis while the heart continues to beat. This removes the need for cardiopulmonary bypass. The stabilisation device is introduced into the chest through an additional port incision.\n\n# Efficacy\n\nFully patent grafts were achieved in 95% (21/22) of patients when assessed at 3 months by postoperative angiography, together with good functional results.\n\nMost case series used duration of operation as a measure and this varied according to the type of procedure undertaken and the number of vessels bypassed. In 45 consecutive patients undergoing TECAB, the mean operating time was 4 hours 12 minutes for single vessel surgery and 6 hours 18 minutes for multiple vessel surgery. In 35 patients, including eight in whom the procedure was performed on the beating heart, the operating time ranged from 3 hours 30 minutes to 8 hours (mean 5 hours 47 minutes). In a further 37 patients (29 of whom had the beating heart procedure), the mean operating time for the early cases in the series was 4 hours 40 minutes, but this was reduced to 3 hours 6 minutes following the introduction of endoscopic stabilisation. The mean length of stay in an intensive care unit varied from 14 hours to 74 hours, and the mean total length of hospital stay ranged from 5.0 to 15.4 days. The upper limits for length of stay were following multiple vessel surgery. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that bleeding could potentially make vessel identification difficult. They also noted that patency rates of coronary bypass grafts were not sufficiently well documented.\n\n# Safety\n\nConversion rates to open procedures (either mini-thoracotomy or full sternotomy) were reported in all case series and ranged from 19% (5/27) to 51% (19/37) of procedures initiated as TECAB.\n\nThere were no cases of operative mortality associated with the TECAB procedure (n = 142).\n\nIn a case series of 45 patients, operative complications included port access failure in 7% (3/45) of patients, prolonged cross clamp time in 9% (4/45), myocardial infarction in 2% (1/45), hypoxic brain damage in 2% (1/45) and internal thoracic artery injury in 2% (1/45) of patients.\n\nIn a series of 45 patients, 4% (2/45) needed secondary intervention because of bleeding from the site of anastomosis. There were no cases of wound infection at the port site throughout the series. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted theoretical complications as myocardial infarction, pneumothorax, cardiac tamponade and fatal haemorrhage. They also noted that there is potential for stenosis or occlusion at the site of anastomosis.\n\n# Other comments\n\nThere are a number of other procedures for treating patients with coronary artery disease but no good studies have been found that compare these with TECAB.", 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedures overview of totally endoscopic robotically assisted coronary artery bypass surgery, November 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.\n\nISBN: 978-1-4731-4017-2'}	https://www.nice.org.uk/guidance/ipg128	Evidence-based recommendations on totally endoscopic robotically assisted coronary artery bypass grafting (TECAB). This involves keyhole surgery using small, remote-controlled robotic arms to carry out the grafting procedure.
8ddeda770680aa9334e19b5d8cc9fd210c96e683	nice	Endovascular stent–graft placement in thoracic aortic aneurysms and dissections	Endovascular stent–graft placement in thoracic aortic aneurysms and dissections # Guidance Current evidence on the safety and efficacy of endovascular stent–graft placement in thoracic aortic aneurysms and dissections indicates that it is a suitable alternative to surgery in appropriately selected patients, provided that the normal arrangements are in place for consent, audit and clinical governance. Clinicians should enter all patients having endovascular stent–graft placement in thoracic aortic aneurysms and dissections into the thoracic stent–graft registry supported by the Vascular Society of Great Britain and Ireland and the British Society of Interventional Radiology. The procedure should be performed by a multidisciplinary team with access to facilities for cardiothoracic surgery and cardiopulmonary bypass.# The procedure # Indications A thoracic aortic aneurysm is a condition in which weakening of the wall of the aorta leads to a localised dilatation of the vessel. In an aortic dissection, there is leakage of blood between the layers of the vessel wall. Aneurysms and dissections may rupture, causing massive internal bleeding. Rupture of the thoracic aorta has high mortality, even with treatment. Conventional surgery for aneurysms of the thoracic aorta involves replacing the affected part of the aorta with a synthetic graft. Aortic dissections may be managed medically or surgically, depending on the site involved and whether there are complicating features. # Outline of the procedure Endovascular stent–graft placement involves inserting a metallic stent covered with graft material inside the aorta. This is usually achieved by catheterising the femoral arteries. The stent–graft is positioned and deployed using X-ray guidance. # Efficacy A systematic review of the published evidence on this procedure was commissioned by the Institute. A total of 29 studies were identified for inclusion (27 case series and two comparative observational studies). In one comparative study, the technical success rate was 100% (67/67 patients). The overall technical success rate was 93% across 18 studies (16 case series and two comparative studies). The rate of conversion to open repair varied from 0% (0/26 patients) to 7% (1/14 patients). The proportion of patients who experienced an increase in aneurysm size varied from 0% (0/18) to 7% (2/29) of patients. In the study with the largest number of patients, the aneurysm increased in size (by ( 5 mm) in 5% (4/84) of patients. The proportion of patients who experienced a decrease in aneurysm size varied from 100% (18/18) to 17% (5/29) of patients. For more details, refer to the Sources of evidence. # Safety The 30-day mortality rate varied from 0% (in several studies with a combined population of 94 patients) to 14% (2/14 patients). The overall mortality ranged from 3% (1/37 patients) to 24% (11/46 patients) across 17 studies with a mean follow-up of 14 months. The most commonly reported complication following endovascular stent–graft placement was endoleak (incomplete sealing of the aneurysm). Nineteen studies reported at least one patient with an endoleak, with a mean incidence of 13% over 12 months (the total number of patients in these studies was 752; follow-up ranged from 3 to 25 months). Five studies with a total of 83 patients reported that there were no cases of endoleak during a mean follow-up period of 12 months. Injuries to the access artery were reported in nine case series, and included iliac artery dissection in 4% (1/26) of patients, perforation of the iliac artery in 4% (1/27) and dissection/rupture of the femoral artery in 6% (2/34) of patients. One case series reported stent fracture in 13% (11/84) of patients, and six cases of stent migration were reported across 15 case series. Other reported complications included wound complications in 25% (8/32) of patients, stroke in 19% (8/43), renal failure requiring dialysis in 11% (2/19) and paraplegia in 7% (3/43) of patients. For more details, refer to the Sources of evidence. # Other comments It was noted that there was a lack of long-term data on the durability of stent–grafts.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. A systematic review of the recent evidence for the efficacy and safety relating to the use of endovascular stent–graft (ESG) placement in the treatment of thoracic aortic aneurysms, February 2005. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': 'Current evidence on the safety and efficacy of endovascular stent–graft placement in thoracic aortic aneurysms and dissections indicates that it is a suitable alternative to surgery in appropriately selected patients, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians should enter all patients having endovascular stent–graft placement in thoracic aortic aneurysms and dissections into the thoracic stent–graft registry supported by the Vascular Society of Great Britain and Ireland and the British Society of Interventional Radiology.\n\nThe procedure should be performed by a multidisciplinary team with access to facilities for cardiothoracic surgery and cardiopulmonary bypass.', 'The procedure': '# Indications\n\nA thoracic aortic aneurysm is a condition in which weakening of the wall of the aorta leads to a localised dilatation of the vessel. In an aortic dissection, there is leakage of blood between the layers of the vessel wall. Aneurysms and dissections may rupture, causing massive internal bleeding. Rupture of the thoracic aorta has high mortality, even with treatment.\n\nConventional surgery for aneurysms of the thoracic aorta involves replacing the affected part of the aorta with a synthetic graft. Aortic dissections may be managed medically or surgically, depending on the site involved and whether there are complicating features.\n\n# Outline of the procedure\n\nEndovascular stent–graft placement involves inserting a metallic stent covered with graft material inside the aorta. This is usually achieved by catheterising the femoral arteries. The stent–graft is positioned and deployed using X-ray guidance.\n\n# Efficacy\n\nA systematic review of the published evidence on this procedure was commissioned by the Institute. A total of 29 studies were identified for inclusion (27 case series and two comparative observational studies).\n\nIn one comparative study, the technical success rate was 100% (67/67 patients). The overall technical success rate was 93% across 18 studies (16 case series and two comparative studies).\n\nThe rate of conversion to open repair varied from 0% (0/26 patients) to 7% (1/14 patients). The proportion of patients who experienced an increase in aneurysm size varied from 0% (0/18) to 7% (2/29) of patients. In the study with the largest number of patients, the aneurysm increased in size (by ( 5 mm) in 5% (4/84) of patients. The proportion of patients who experienced a decrease in aneurysm size varied from 100% (18/18) to 17% (5/29) of patients. For more details, refer to the Sources of evidence.\n\n# Safety\n\nThe 30-day mortality rate varied from 0% (in several studies with a combined population of 94 patients) to 14% (2/14 patients). The overall mortality ranged from 3% (1/37 patients) to 24% (11/46 patients) across 17 studies with a mean follow-up of 14 months.\n\nThe most commonly reported complication following endovascular stent–graft placement was endoleak (incomplete sealing of the aneurysm). Nineteen studies reported at least one patient with an endoleak, with a mean incidence of 13% over 12 months (the total number of patients in these studies was 752; follow-up ranged from 3 to 25 months). Five studies with a total of 83 patients reported that there were no cases of endoleak during a mean follow-up period of 12 months.\n\nInjuries to the access artery were reported in nine case series, and included iliac artery dissection in 4% (1/26) of patients, perforation of the iliac artery in 4% (1/27) and dissection/rupture of the femoral artery in 6% (2/34) of patients. One case series reported stent fracture in 13% (11/84) of patients, and six cases of stent migration were reported across 15 case series.\n\nOther reported complications included wound complications in 25% (8/32) of patients, stroke in 19% (8/43), renal failure requiring dialysis in 11% (2/19) and paraplegia in 7% (3/43) of patients. For more details, refer to the Sources of evidence.\n\n# Other comments\n\nIt was noted that there was a lack of long-term data on the durability of stent–grafts.', 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nA systematic review of the recent evidence for the efficacy and safety relating to the use of endovascular stent–graft (ESG) placement in the treatment of thoracic aortic aneurysms, February 2005.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg127
b18cdca1ed70ef3fdd02013782f2b5e6736e1737	nice	Computed tomographic colonography (virtual colonoscopy)	Computed tomographic colonography (virtual colonoscopy) # Guidance Current evidence on the safety and efficacy of computed tomographic colonography (virtual colonoscopy) appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.# The procedure # Indications Computed tomographic (CT) colonography is used to examine the colon and rectum to detect abnormalities such as polyps and cancer. Polyps may be adenomatous (which have the potential to become malignant) or completely benign. Colorectal cancer is the second most common cancer in women and the third most common cancer in men in the UK. Symptoms include blood in the stool, change in bowel habit, abdominal pain and unexplained weight loss. In addition to its use as a diagnostic test in symptomatic patients, CT colonography may be used in asymptomatic patients with a high risk of developing colorectal cancer. Conventional colonoscopy and double-contrast barium enema are the main methods currently used for examining the colon. # Outline of the procedure CT colonography involves using a CT scanner to produce two- and three-dimensional images of the entire colon and rectum. CT colonography is less invasive than conventional colonoscopy. CT colonography is usually performed on an empty bowel although 'faecal tagging' may be used, which eliminates the need for a cathartic bowel preparation. Faecal tagging requires the patient to ingest an iodinated contrast agent with meals approximately 48 hours before the scan. Sedation is not usually required for CT colonography. The colon is distended by insufflation with air or carbon dioxide via a small rectal tube. Antispasmodic agents and/or contrast agents may be administered intravenously before the scan. The images are manipulated and interpreted by a radiologist. # Efficacy A meta-analysis of data from 14 studies with a total of 1324 patients reported the sensitivity and specificity of CT colonography for the detection of polyps, using conventional colonoscopy as the reference standard. The pooled per-patient sensitivity for polyps 10 mm or larger was 88% (95% confidence interval , 84–93%), for polyps 6–9 mm it was 84% (95% CI, 80–89%), and for polyps 5 mm or smaller it was 65% (95% CI, 57–73%). The pooled per-polyp sensitivity for polyps 10 mm or larger was 81% (95% CI, 76–85%), for polyps 6–9 mm it was 62% (95% CI, 58–67%), and for polyps 5 mm or smaller it was 43% (95% CI, 39–47%). The overall specificity for the detection of polyps 10 mm or larger was 95% (95% CI, 94–97%). A study involving 1233 asymptomatic adults reported that the per-patient sensitivity for polyps 10 mm or larger was 94% (95% CI, 83–99%) for CT colonography and 88% (95% CI, 75–95%) for conventional colonoscopy. The per-patient sensitivity for polyps 6 mm or larger was 89% (95% CI, 83–93%) for CT colonography and 92% (95% CI, 87–96%) for conventional colonoscopy. A study of 615 patients reported per-patient sensitivities of 55% (95% CI, 40–70%) for polyps 10 mm or larger and 39% (95% CI, 30–48%) for polyps 6 mm or larger. Another study of 614 patients reported that CT colonography was significantly more sensitive than barium enema but less sensitive than colonoscopy. A study of 203 patients that used faecal tagging reported an overall per-patient sensitivity of 90% (95% CI, 86–94%). For more details, refer to the Sources of evidence. The Specialist Advisors noted that the procedure may fail to detect small or flat lesions, but commented that this was also the case with other diagnostic techniques. # Safety No significant complications were reported in the studies. Two studies reported on the level of discomfort felt by patients during the procedure. One study reported that 1% (9/696) of patients experienced 'extreme' or 'severe' discomfort during CT colonography, compared with 4% (25/696) for colonoscopy. In the same study, less than 1% (4/617) of patients had 'extreme' or 'severe' discomfort during CT colonography compared with 29% (181/617) during a barium enema (p < 0.001). A second study reported that 54% (546/1005) of patients found CT colonography to be more uncomfortable than conventional colonoscopy, but this may have been affected by the fact that patients were sedated for the conventional colonoscopy but not for the CT colonography. In the same study, CT colonography was reported to be more acceptable in terms of convenience than conventional colonoscopy in 68% (686/1005) of patients. In one study, 72% (357/494) of patients were reported to prefer CT colonography to conventional colonoscopy, and 97% (518/534) preferred CT colonography to double-contrast barium enema. For more details, refer to the Sources of evidence. The Specialist Advisors noted that the potential complications are similar to those associated with other techniques, and include bowel perforation and reaction to the intravenous contrast medium. # Other comments It was noted that this is a rapidly evolving technology, dependent on the type of equipment used and the training and experience of the operator. It was noted that patient selection was important; this is an alternative procedure to barium enema, and is particularly useful in frail and elderly patients as a diagnostic tool to detect tumours.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedure overview of computed tomographic colonography (virtual colonoscopy), August 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': 'Current evidence on the safety and efficacy of computed tomographic colonography (virtual colonoscopy) appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.', 'The procedure': "# Indications\n\nComputed tomographic (CT) colonography is used to examine the colon and rectum to detect abnormalities such as polyps and cancer. Polyps may be adenomatous (which have the potential to become malignant) or completely benign.\n\nColorectal cancer is the second most common cancer in women and the third most common cancer in men in the UK. Symptoms include blood in the stool, change in bowel habit, abdominal pain and unexplained weight loss. In addition to its use as a diagnostic test in symptomatic patients, CT colonography may be used in asymptomatic patients with a high risk of developing colorectal cancer.\n\nConventional colonoscopy and double-contrast barium enema are the main methods currently used for examining the colon.\n\n# Outline of the procedure\n\nCT colonography involves using a CT scanner to produce two- and three-dimensional images of the entire colon and rectum. CT colonography is less invasive than conventional colonoscopy.\n\nCT colonography is usually performed on an empty bowel although 'faecal tagging' may be used, which eliminates the need for a cathartic bowel preparation. Faecal tagging requires the patient to ingest an iodinated contrast agent with meals approximately 48 hours before the scan. Sedation is not usually required for CT colonography. The colon is distended by insufflation with air or carbon dioxide via a small rectal tube. Antispasmodic agents and/or contrast agents may be administered intravenously before the scan. The images are manipulated and interpreted by a radiologist.\n\n# Efficacy\n\nA meta-analysis of data from 14 studies with a total of 1324 patients reported the sensitivity and specificity of CT colonography for the detection of polyps, using conventional colonoscopy as the reference standard. The pooled per-patient sensitivity for polyps 10 mm or larger was 88% (95% confidence interval [CI], 84–93%), for polyps 6–9 mm it was 84% (95% CI, 80–89%), and for polyps 5 mm or smaller it was 65% (95% CI, 57–73%). The pooled per-polyp sensitivity for polyps 10 mm or larger was 81% (95% CI, 76–85%), for polyps 6–9 mm it was 62% (95% CI, 58–67%), and for polyps 5 mm or smaller it was 43% (95% CI, 39–47%). The overall specificity for the detection of polyps 10 mm or larger was 95% (95% CI, 94–97%).\n\nA study involving 1233 asymptomatic adults reported that the per-patient sensitivity for polyps 10 mm or larger was 94% (95% CI, 83–99%) for CT colonography and 88% (95% CI, 75–95%) for conventional colonoscopy. The per-patient sensitivity for polyps 6 mm or larger was 89% (95% CI, 83–93%) for CT colonography and 92% (95% CI, 87–96%) for conventional colonoscopy. A study of 615 patients reported per-patient sensitivities of 55% (95% CI, 40–70%) for polyps 10 mm or larger and 39% (95% CI, 30–48%) for polyps 6 mm or larger. Another study of 614 patients reported that CT colonography was significantly more sensitive than barium enema but less sensitive than colonoscopy. A study of 203 patients that used faecal tagging reported an overall per-patient sensitivity of 90% (95% CI, 86–94%). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that the procedure may fail to detect small or flat lesions, but commented that this was also the case with other diagnostic techniques.\n\n# Safety\n\nNo significant complications were reported in the studies. Two studies reported on the level of discomfort felt by patients during the procedure. One study reported that 1% (9/696) of patients experienced 'extreme' or 'severe' discomfort during CT colonography, compared with 4% (25/696) for colonoscopy. In the same study, less than 1% (4/617) of patients had 'extreme' or 'severe' discomfort during CT colonography compared with 29% (181/617) during a barium enema (p < 0.001). A second study reported that 54% (546/1005) of patients found CT colonography to be more uncomfortable than conventional colonoscopy, but this may have been affected by the fact that patients were sedated for the conventional colonoscopy but not for the CT colonography. In the same study, CT colonography was reported to be more acceptable in terms of convenience than conventional colonoscopy in 68% (686/1005) of patients.\n\nIn one study, 72% (357/494) of patients were reported to prefer CT colonography to conventional colonoscopy, and 97% (518/534) preferred CT colonography to double-contrast barium enema. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that the potential complications are similar to those associated with other techniques, and include bowel perforation and reaction to the intravenous contrast medium.\n\n# Other comments\n\nIt was noted that this is a rapidly evolving technology, dependent on the type of equipment used and the training and experience of the operator.\n\nIt was noted that patient selection was important; this is an alternative procedure to barium enema, and is particularly useful in frail and elderly patients as a diagnostic tool to detect tumours.", 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedure overview of computed tomographic colonography (virtual colonoscopy), August 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg129
71cdcbb65f0ba8ee7eff330d16d8a2c925674977	nice	Cryotherapy for recurrent prostate cancer	Cryotherapy for recurrent prostate cancer # Guidance Current evidence on the safety and efficacy of cryotherapy, as measured by a reduction of prostate-specific antigen (PSA) levels and biopsy findings, appears adequate to support the use of this procedure in patients with recurrent prostate cancer provided that the normal arrangements are in place for consent, audit and clinical governance. The effects of cryotherapy for recurrent prostate cancer on quality of life and long-term survival remain uncertain. Clinicians should therefore ensure that patients understand the uncertainties and the alternative treatment options. Use of NICE's information for the public is recommended. Further research and audit should address quality of life, clinical outcomes and long-term survival.# The procedure # Indications Cryotherapy may be used to treat locally recurrent carcinoma of the prostate that has been refractory to other treatments, such as radiotherapy or hormone therapy. Treatment options for locally recurrent prostate cancer after radiotherapy are limited and include salvage radical prostatectomy, salvage cryotherapy and salvage brachytherapy. # Outline of the procedure Cryotherapy may be performed under general or spinal anaesthesia. A warming catheter is initially inserted into the urethra to prevent it being damaged by the cold. Cryoneedles or probes are inserted into the prostate, using imaging for guidance. Temperature monitor probes may also be placed percutaneously through the perineum. Argon gas is then circulated through these needles or probes, generating very low temperatures and causing the formation of ice around the prostate gland which destroys the affected tissue. Newer cryotherapy techniques allow these needles to be removed or repositioned so that the frozen zone conforms to the exact size and shape of the target tissue. After the procedure, a suprapubic catheter is inserted and left in place for 1–2 weeks, depending on the post-void residual urine volume. # Efficacy Various efficacy outcome measures were used in the studies identified, making comparisons of efficacy across studies difficult. A frequently used marker was PSA, a protein produced by both normal and cancerous cells in the prostate gland. Reduction in the PSA level is used as a marker for ablation of malignant tissue in studies of prostate cancer treatment, together with negative prostatic biopsies. In one study, lowest level PSA < 0.5 ng/ml was reported in 97% (114/118) of patients who had undergone cryotherapy; in another study, a level of < 0.1 ng/ml was reported in 60% (26/43) of patients. These studies included patients with recurrent prostate cancer or rising PSA levels, and those who were undergoing salvage therapy. After medial retropubic prostatectomy, PSA levels are expected to be < 0.1 ng/ml. In a study of 43 patients, biochemical-recurrence-free survival (recurrence defined as an increase in PSA level of > 0.2 ng/ml above nadir) was reported as 79% at 6 months and 66% at 12 months; and in a study of 38 patients (recurrence defined as an increase in PSA level of > 0.3 ng/ml above nadir), as 86% at 12 months and 74% at 24 months. One case series reported negative biopsy in 100% (38/38) of patients followed up for a median 82 months. Another case series reported negative biopsies in 79% (87/110) of patients at 6-month follow-up. For more details, refer to the Sources of evidence. # Safety Complication rates varied substantially among the studies and there is some evidence to suggest that complications have decreased with improvements in technique and instrumentation. Among the studies identified, the following complications were reported: impotence in 72% (108/150) and 86% (12/14) of patients; incontinence in 8% (3/38) of patients; and perineal and/or rectal pain in 18% (27/150) to 39% (15/38) of patients. Other reported complications from the case series included fistula formation in 1% (2/150) to 3% (4/118 and 2/59) of patients. For more details, refer to the Sources of evidence. The Specialist Advisors listed the main complications as urinary incontinence, impotence, rectal injury and fistula formation. However, severe complications are rare and comparison needs to be made with the complication rates in alternative options. # Other comments In recommending that further research and audit should address long-term survival, it is noted that prostate cancer patients frequently die from unrelated causes. There are different types of cryotherapy device, and these may have different safety profiles. The technology for this procedure is continuing to evolve.# Other NICE recommendations on cryotherapy for the treatment of prostate cancer Further recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008, as follows: High intensity focused ultrasound (HIFU) and cryotherapy are not recommended for men with localised prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions. Clinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information on prostate cancer diagnosis and management is available. The IP guidance on cryotherapy for recurrent prostate cancer remains current, and should be read in conjunction with the clinical guideline.# Further information NICE has issued guidance on urological cancer services, which includes prostate cancer. The Institute has also issued interventional procedures guidance on laparoscopic radical prostatectomy and high-intensity ultrasound for prostate cancer. # Sources of evidence The following document, which summarises the evidence, was considered by the Institute when making its recommendations. Interventional procedure overview of cryotherapy for recurrent prostate cancer, June 2004. # Information for patients NICE has produced information on this procedure for the patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of cryotherapy, as measured by a reduction of prostate-specific antigen (PSA) levels and biopsy findings, appears adequate to support the use of this procedure in patients with recurrent prostate cancer provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe effects of cryotherapy for recurrent prostate cancer on quality of life and long-term survival remain uncertain. Clinicians should therefore ensure that patients understand the uncertainties and the alternative treatment options. Use of NICE's information for the public is recommended.\n\nFurther research and audit should address quality of life, clinical outcomes and long-term survival.", 'The procedure': '# Indications\n\nCryotherapy may be used to treat locally recurrent carcinoma of the prostate that has been refractory to other treatments, such as radiotherapy or hormone therapy.\n\nTreatment options for locally recurrent prostate cancer after radiotherapy are limited and include salvage radical prostatectomy, salvage cryotherapy and salvage brachytherapy.\n\n# Outline of the procedure\n\nCryotherapy may be performed under general or spinal anaesthesia. A warming catheter is initially inserted into the urethra to prevent it being damaged by the cold. Cryoneedles or probes are inserted into the prostate, using imaging for guidance. Temperature monitor probes may also be placed percutaneously through the perineum. Argon gas is then circulated through these needles or probes, generating very low temperatures and causing the formation of ice around the prostate gland which destroys the affected tissue. Newer cryotherapy techniques allow these needles to be removed or repositioned so that the frozen zone conforms to the exact size and shape of the target tissue. After the procedure, a suprapubic catheter is inserted and left in place for 1–2 weeks, depending on the post-void residual urine volume.\n\n# Efficacy\n\nVarious efficacy outcome measures were used in the studies identified, making comparisons of efficacy across studies difficult. A frequently used marker was PSA, a protein produced by both normal and cancerous cells in the prostate gland. Reduction in the PSA level is used as a marker for ablation of malignant tissue in studies of prostate cancer treatment, together with negative prostatic biopsies.\n\nIn one study, lowest level PSA < 0.5 ng/ml was reported in 97% (114/118) of patients who had undergone cryotherapy; in another study, a level of < 0.1 ng/ml was reported in 60% (26/43) of patients. These studies included patients with recurrent prostate cancer or rising PSA levels, and those who were undergoing salvage therapy. After medial retropubic prostatectomy, PSA levels are expected to be < 0.1 ng/ml.\n\nIn a study of 43 patients, biochemical-recurrence-free survival (recurrence defined as an increase in PSA level of > 0.2 ng/ml above nadir) was reported as 79% at 6 months and 66% at 12 months; and in a study of 38 patients (recurrence defined as an increase in PSA level of > 0.3 ng/ml above nadir), as 86% at 12 months and 74% at 24 months. One case series reported negative biopsy in 100% (38/38) of patients followed up for a median 82 months. Another case series reported negative biopsies in 79% (87/110) of patients at 6-month follow-up. For more details, refer to the Sources of evidence.\n\n# Safety\n\nComplication rates varied substantially among the studies and there is some evidence to suggest that complications have decreased with improvements in technique and instrumentation. Among the studies identified, the following complications were reported: impotence in 72% (108/150) and 86% (12/14) of patients; incontinence in 8% (3/38) of patients; and perineal and/or rectal pain in 18% (27/150) to 39% (15/38) of patients. Other reported complications from the case series included fistula formation in 1% (2/150) to 3% (4/118 and 2/59) of patients. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors listed the main complications as urinary incontinence, impotence, rectal injury and fistula formation. However, severe complications are rare and comparison needs to be made with the complication rates in alternative options.\n\n# Other comments\n\nIn recommending that further research and audit should address long-term survival, it is noted that prostate cancer patients frequently die from unrelated causes.\n\nThere are different types of cryotherapy device, and these may have different safety profiles.\n\nThe technology for this procedure is continuing to evolve.', 'Other NICE recommendations on cryotherapy for the treatment of prostate cancer': 'Further recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008, as follows:\n\nHigh intensity focused ultrasound (HIFU) and cryotherapy are not recommended for men with localised prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions.\n\nClinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information on prostate cancer diagnosis and management is available. The IP guidance on cryotherapy for recurrent prostate cancer remains current, and should be read in conjunction with the clinical guideline.', 'Further information': 'NICE has issued guidance on urological cancer services, which includes prostate cancer. The Institute has also issued interventional procedures guidance on laparoscopic radical prostatectomy and high-intensity ultrasound for prostate cancer.\n\n# Sources of evidence\n\nThe following document, which summarises the evidence, was considered by the Institute when making its recommendations.\n\nInterventional procedure overview of cryotherapy for recurrent prostate cancer, June 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for the patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg119
c9efa0e1865e84e06513cf5a180a6ec5d9aa2c73	nice	Microwave ablation for atrial fibrillation in association with other cardiac surgery	Microwave ablation for atrial fibrillation in association with other cardiac surgery # Guidance Current evidence on the safety and efficacy of microwave ablation for atrial fibrillation in association with other cardiac surgery appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Patient selection and follow-up should be carried out by a multidisciplinary team. Cardiac surgeons undertaking this procedure should have specific training in the use of microwave energy equipment.# The procedure # Indications Atrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It may be classified as paroxysmal, persistent or permanent. It is the most common type of arrhythmia and the incidence increases markedly with age. Patients with atrial fibrillation may be asymptomatic or they may have symptoms such as palpitations, dizziness and breathlessness. They also have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain. Atrial fibrillation usually occurs in the absence of structural heart disease. However, if structural heart disease is present, it is most commonly mitral stenosis. Conservative treatments include medication, electrical cardioversion to control the heart rhythm and anticoagulants to prevent the formation of blood clots. The conventional surgical approach, known as the Cox maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative methods of creating lesions in the atria by ablation have been developed, using energy sources such as radiofrequency, cryotherapy and ultrasound. # Outline of the procedure Microwave ablation for atrial fibrillation is typically carried out in patients undergoing concomitant open heart surgery (often mitral valve replacement or repair). The procedure uses thermal damage, rather than incisions, to block impulse conduction. The heat generated by a flexible microwave probe coagulates the heart tissue, forming linear scars or lesions that disrupt the transmission of the abnormal electrical impulses. The procedure may be carried out on both atria or on the left atrium only. It can be performed from within or outside the atrium. # Efficacy In one randomised controlled trial, patients treated with open heart surgery and microwave ablation were compared with those treated with open heart surgery alone. Immediately after the surgery, 92% (22/24) of patients who had microwave ablation were in sinus rhythm compared with 32% (6/19) of patients in the control group (p = 0.05). At 12 months, 80% (12/15) of patients who had microwave ablation were in sinus rhythm compared with 33% (3/9) of control patients (p < 0.05). A non-randomised controlled trial reported that 62% (84/136) of patients treated with microwave ablation were in sinus rhythm at 12 months, compared with 10% (5/51) of patients having heart surgery without microwave ablation (p = 0.0001). A second non-randomised controlled trial that compared patients who had microwave ablation with those who had radiofrequency ablation reported no significant difference in the number of patients in sinus rhythm at 12 months; the results were 59% (13/22) for the microwave ablation group and 57% (8/14) for the radiofrequency ablation group. Case series reported that 61% (25/41) and 76% (32/42) of patients who had microwave ablation were in sinus rhythm immediately after surgery. In a further case series, 62% (74/119) of patients were in sinus rhythm at 12-month follow-up. For more details, refer to the Sources of evidence. The Specialist Advisors considered this procedure to be a variation on the Cox maze technique. # Safety This procedure is performed during open heart surgery; therefore it is difficult to differentiate the complications that relate specifically to microwave ablation. The main complications reported were in-hospital mortality and the requirement for a permanent pacemaker. In the randomised controlled trial, the in-hospital mortality was 4% (1/24) for patients treated with microwave ablation and heart surgery, compared with 5% (1/19) for patients who had heart surgery only. Four other studies reported in-hospital mortality rates, which ranged from 0% (0/42) to 4% (1/23). Four studies reported the proportion of patients who needed a permanent pacemaker; this ranged from 0% (0/41) to 23% (46/202). One study reported additional complications of bleeding in 9% (2/23) of patients; the need for an intra-aortic balloon pump in 4% (1/23); transient low cardiac output in 4% (1/23); and severe systemic inflammatory response syndrome in 4% (1/23). For more details, refer to the Sources of evidence. The Specialist Advisors listed the potential adverse events as oesophageal injury, heart block, intra-operative myocardial infarction and excessive tissue damage. # Other comments Most of the data were on patients having mitral valve surgery. There was only limited evidence on the efficacy of microwave ablation when performed with other procedures such as coronary artery bypass grafting. This procedure appears to be more efficacious in patients whose atrial fibrillation has been of short duration (less than 1 year). It was noted that there are variations in technique and microwave energy settings used for this procedure. It was also noted that it may be difficult to determine when full-thickness ablation has been achieved.# Further information NICE has published interventional procedures guidance on radiofrequency ablation for atrial fibrillation and cryoablation for atrial fibrillation. NICE is also currently developing a guideline for the diagnosis and treatment of atrial fibrillation . # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedure overview of microwave ablation for atrial fibrillation in association with other cardiac surgery, December 2004. # Information for patients NICE has produced information on this procedure for the public. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': 'Current evidence on the safety and efficacy of microwave ablation for atrial fibrillation in association with other cardiac surgery appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nPatient selection and follow-up should be carried out by a multidisciplinary team. Cardiac surgeons undertaking this procedure should have specific training in the use of microwave energy equipment.', 'The procedure': '# Indications\n\nAtrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It may be classified as paroxysmal, persistent or permanent. It is the most common type of arrhythmia and the incidence increases markedly with age. Patients with atrial fibrillation may be asymptomatic or they may have symptoms such as palpitations, dizziness and breathlessness. They also have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain.\n\nAtrial fibrillation usually occurs in the absence of structural heart disease. However, if structural heart disease is present, it is most commonly mitral stenosis.\n\nConservative treatments include medication, electrical cardioversion to control the heart rhythm and anticoagulants to prevent the formation of blood clots. The conventional surgical approach, known as the Cox maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative methods of creating lesions in the atria by ablation have been developed, using energy sources such as radiofrequency, cryotherapy and ultrasound.\n\n# Outline of the procedure\n\nMicrowave ablation for atrial fibrillation is typically carried out in patients undergoing concomitant open heart surgery (often mitral valve replacement or repair). The procedure uses thermal damage, rather than incisions, to block impulse conduction. The heat generated by a flexible microwave probe coagulates the heart tissue, forming linear scars or lesions that disrupt the transmission of the abnormal electrical impulses. The procedure may be carried out on both atria or on the left atrium only. It can be performed from within or outside the atrium.\n\n# Efficacy\n\nIn one randomised controlled trial, patients treated with open heart surgery and microwave ablation were compared with those treated with open heart surgery alone. Immediately after the surgery, 92% (22/24) of patients who had microwave ablation were in sinus rhythm compared with 32% (6/19) of patients in the control group (p = 0.05). At 12 months, 80% (12/15) of patients who had microwave ablation were in sinus rhythm compared with 33% (3/9) of control patients (p < 0.05). A non-randomised controlled trial reported that 62% (84/136) of patients treated with microwave ablation were in sinus rhythm at 12 months, compared with 10% (5/51) of patients having heart surgery without microwave ablation (p = 0.0001). A second non-randomised controlled trial that compared patients who had microwave ablation with those who had radiofrequency ablation reported no significant difference in the number of patients in sinus rhythm at 12 months; the results were 59% (13/22) for the microwave ablation group and 57% (8/14) for the radiofrequency ablation group.\n\nCase series reported that 61% (25/41) and 76% (32/42) of patients who had microwave ablation were in sinus rhythm immediately after surgery. In a further case series, 62% (74/119) of patients were in sinus rhythm at 12-month follow-up. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors considered this procedure to be a variation on the Cox maze technique.\n\n# Safety\n\nThis procedure is performed during open heart surgery; therefore it is difficult to differentiate the complications that relate specifically to microwave ablation.\n\nThe main complications reported were in-hospital mortality and the requirement for a permanent pacemaker. In the randomised controlled trial, the in-hospital mortality was 4% (1/24) for patients treated with microwave ablation and heart surgery, compared with 5% (1/19) for patients who had heart surgery only. Four other studies reported in-hospital mortality rates, which ranged from 0% (0/42) to 4% (1/23). Four studies reported the proportion of patients who needed a permanent pacemaker; this ranged from 0% (0/41) to 23% (46/202). One study reported additional complications of bleeding in 9% (2/23) of patients; the need for an intra-aortic balloon pump in 4% (1/23); transient low cardiac output in 4% (1/23); and severe systemic inflammatory response syndrome in 4% (1/23). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors listed the potential adverse events as oesophageal injury, heart block, intra-operative myocardial infarction and excessive tissue damage.\n\n# Other comments\n\nMost of the data were on patients having mitral valve surgery. There was only limited evidence on the efficacy of microwave ablation when performed with other procedures such as coronary artery bypass grafting.\n\nThis procedure appears to be more efficacious in patients whose atrial fibrillation has been of short duration (less than 1 year).\n\nIt was noted that there are variations in technique and microwave energy settings used for this procedure. It was also noted that it may be difficult to determine when full-thickness ablation has been achieved.', 'Further information': 'NICE has published interventional procedures guidance on radiofrequency ablation for atrial fibrillation and cryoablation for atrial fibrillation. NICE is also currently developing a guideline for the diagnosis and treatment of atrial fibrillation [now published as Atrial fibrillation: diagnosis and management].\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedure overview of microwave ablation for atrial fibrillation in association with other cardiac surgery, December 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for the public. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg122
96047c3ea7a672dabb18e83db349b50068b812a1	nice	Cryoablation for atrial fibrillation in association with other cardiac surgery	Cryoablation for atrial fibrillation in association with other cardiac surgery # Guidance Current evidence on the safety and efficacy of cryoablation for atrial fibrillation in association with other cardiac surgery appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Patient selection and follow-up should be carried out by a multidisciplinary team. Cardiac surgeons undertaking this procedure should have specific training in the use of cryoablation equipment.# The procedure # Indications Atrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It may be classified as paroxysmal, persistent or permanent. It is the most common type of arrhythmia and the incidence increases markedly with age. Patients with atrial fibrillation may be asymptomatic or they may have symptoms such as palpitations, dizziness and breathlessness. They also have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain. Atrial fibrillation usually occurs in the absence of structural heart disease. However, if structural heart disease is present, it is most commonly mitral stenosis. Conservative treatments include medication, electrical cardioversion to control the heart rhythm, and anticoagulants to prevent the formation of blood clots. The conventional surgical approach, known as the Cox maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative methods of creating lesions in the atria by ablation have been developed, using energy sources such as radiofrequency, microwave and ultrasound. # Outline of the procedure Cryoablation for atrial fibrillation is typically carried out in patients undergoing concomitant open heart surgery (often mitral valve replacement or repair). A cryoprobe is used to freeze heart tissue. The damaged tissue forms linear scars or lesions that disrupt the transmission of the abnormal electrical impulses. The procedure may be carried out on both atria or on the left atrium only. It can be performed from within or outside the atrium. # Efficacy One non-randomised trial compared patients treated with mitral valve surgery and cryoablation with patients who had mitral valve surgery and the Cox maze procedure. At discharge, 85% (94/110) of patients treated with cryoablation were in sinus rhythm, compared with 86% (95/110) of patients treated with the Cox maze procedure (p = 0.84). The survival rate at 3 years was 92% for the cryotherapy group and 98% for the Cox maze group (p = 0.32). Two non-randomised trials compared patients who had cryoablation and concomitant heart valve surgery with patients who had heart valve surgery only. In the cryoablation groups, 100% (36/36) and 78% (25/32) of patients were in sinus rhythm immediately after surgery, compared with 33% (5/15) and 22% (4/18) of patients in the control groups. In one of these trials, 90% (26/29) of patients treated with cryoablation were in sinus rhythm at 9 months, compared with 25% (4/16) of patients in the control group. In the other trial, 78% (28/36) of patients treated with cryoablation and 20% (3/15) of patients in the control group were in sinus rhythm at 6 months. For more details, refer to the Sources of evidence. The Specialist Advisors considered this procedure to be a variation on the Cox maze technique. # Safety This procedure is performed during open heart surgery; therefore it is difficult to differentiate the complications that relate specifically to cryoablation. Three studies reported in-hospital mortality, which ranged from 0% (0/28) to 3% (3/95, 1/32). In four studies, 3% (1/32) to 14% (4/28) of patients required a pacemaker following surgery. Other complications included re-operation; delayed cardiac tamponade; mediastinitis; low cardiac output; the need for an intra-aortic balloon pump; dialysis; and transient ischaemic attack. For more details, refer to the Sources of evidence. The Specialist Advisors noted that oesophageal injury, heart block, damage to the circumflex coronary artery and intra-operative myocardial infarction were potential adverse effects of the procedure. # Other comments Most of the data were on patients having mitral valve surgery. There was only limited evidence on the efficacy of cryoablation when performed with other procedures such as coronary artery bypass grafting. This procedure appears to be more efficacious in patients whose atrial fibrillation has been of short duration (less than 1 year). It was noted that there are variations in technique and cryotherapy parameters used for this procedure. It was also noted that it may be difficult to determine when a full-thickness ablation has been achieved.# Further information NICE has published interventional procedures guidance on radiofrequency ablation for atrial fibrillation and microwave ablation for atrial fibrillation. NICE is also currently developing a guideline for the diagnosis and treatment of atrial fibrillation . # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedures overview of cryoablation for atrial fibrillation as an associated procedure with other cardiac surgery, December 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': 'Current evidence on the safety and efficacy of cryoablation for atrial fibrillation in association with other cardiac surgery appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nPatient selection and follow-up should be carried out by a multidisciplinary team. Cardiac surgeons undertaking this procedure should have specific training in the use of cryoablation equipment.', 'The procedure': '# Indications\n\nAtrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It may be classified as paroxysmal, persistent or permanent. It is the most common type of arrhythmia and the incidence increases markedly with age. Patients with atrial fibrillation may be asymptomatic or they may have symptoms such as palpitations, dizziness and breathlessness. They also have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain.\n\nAtrial fibrillation usually occurs in the absence of structural heart disease. However, if structural heart disease is present, it is most commonly mitral stenosis.\n\nConservative treatments include medication, electrical cardioversion to control the heart rhythm, and anticoagulants to prevent the formation of blood clots. The conventional surgical approach, known as the Cox maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative methods of creating lesions in the atria by ablation have been developed, using energy sources such as radiofrequency, microwave and ultrasound.\n\n# Outline of the procedure\n\nCryoablation for atrial fibrillation is typically carried out in patients undergoing concomitant open heart surgery (often mitral valve replacement or repair). A cryoprobe is used to freeze heart tissue. The damaged tissue forms linear scars or lesions that disrupt the transmission of the abnormal electrical impulses. The procedure may be carried out on both atria or on the left atrium only. It can be performed from within or outside the atrium.\n\n# Efficacy\n\nOne non-randomised trial compared patients treated with mitral valve surgery and cryoablation with patients who had mitral valve surgery and the Cox maze procedure. At discharge, 85% (94/110) of patients treated with cryoablation were in sinus rhythm, compared with 86% (95/110) of patients treated with the Cox maze procedure (p = 0.84). The survival rate at 3 years was 92% for the cryotherapy group and 98% for the Cox maze group (p = 0.32).\n\nTwo non-randomised trials compared patients who had cryoablation and concomitant heart valve surgery with patients who had heart valve surgery only. In the cryoablation groups, 100% (36/36) and 78% (25/32) of patients were in sinus rhythm immediately after surgery, compared with 33% (5/15) and 22% (4/18) of patients in the control groups. In one of these trials, 90% (26/29) of patients treated with cryoablation were in sinus rhythm at 9 months, compared with 25% (4/16) of patients in the control group. In the other trial, 78% (28/36) of patients treated with cryoablation and 20% (3/15) of patients in the control group were in sinus rhythm at 6 months. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors considered this procedure to be a variation on the Cox maze technique.\n\n# Safety\n\nThis procedure is performed during open heart surgery; therefore it is difficult to differentiate the complications that relate specifically to cryoablation.\n\nThree studies reported in-hospital mortality, which ranged from 0% (0/28) to 3% (3/95, 1/32). In four studies, 3% (1/32) to 14% (4/28) of patients required a pacemaker following surgery. Other complications included re-operation; delayed cardiac tamponade; mediastinitis; low cardiac output; the need for an intra-aortic balloon pump; dialysis; and transient ischaemic attack. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors noted that oesophageal injury, heart block, damage to the circumflex coronary artery and intra-operative myocardial infarction were potential adverse effects of the procedure.\n\n# Other comments\n\nMost of the data were on patients having mitral valve surgery. There was only limited evidence on the efficacy of cryoablation when performed with other procedures such as coronary artery bypass grafting.\n\nThis procedure appears to be more efficacious in patients whose atrial fibrillation has been of short duration (less than 1 year).\n\nIt was noted that there are variations in technique and cryotherapy parameters used for this procedure. It was also noted that it may be difficult to determine when a full-thickness ablation has been achieved.', 'Further information': 'NICE has published interventional procedures guidance on radiofrequency ablation for atrial fibrillation and microwave ablation for atrial fibrillation. NICE is also currently developing a guideline for the diagnosis and treatment of atrial fibrillation [now published as Atrial fibrillation: diagnosis and management].\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedures overview of cryoablation for atrial fibrillation as an associated procedure with other cardiac surgery, December 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg123
c11e18184e08eb7375513b0a520a7f55ab87e5fe	nice	Radiofrequency ablation for atrial fibrillation in association with other cardiac surgery	Radiofrequency ablation for atrial fibrillation in association with other cardiac surgery # Guidance Current evidence on the safety and efficacy of radiofrequency ablation (RFA) for atrial fibrillation in association with other cardiac surgery appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Patient selection and follow-up should be carried out by a multidisciplinary team. Cardiac surgeons undertaking this procedure should have specific training in the use of radiofrequency equipment.# The procedure # Indications Atrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It may be classified as paroxysmal, persistent or permanent. It is the most common type of arrhythmia and the incidence increases markedly with age. Patients with atrial fibrillation may be asymptomatic or they may have symptoms such as palpitations, dizziness and breathlessness. They also have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain. Atrial fibrillation usually occurs in the absence of structural heart disease. However, if structural heart disease is present, it is most commonly mitral stenosis. Conservative treatments include medication, electrical cardioversion to control the heart rhythm, and anticoagulants to prevent the formation of blood clots. The conventional surgical approach, known as the Cox maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative methods of creating lesions in the atria by ablation have been developed, using energy sources such as microwave, cryotherapy and ultrasound. # Outline of the procedure Radiofrequency ablation (RFA) for atrial fibrillation is typically carried out in patients undergoing concomitant open heart surgery (often mitral valve replacement or repair). The procedure uses thermal damage, rather than incisions, to block impulse conduction. The heat generated coagulates the heart tissue, forming linear scars or lesions that disrupt the transmission of the abnormal electrical impulses. The procedure may be carried out on both atria or on the left atrium only. It can be performed from within or outside the atrium. # Efficacy In one small randomised controlled trial, 82% (9/11) of patients treated with atrial RFA and a mitral valve replacement were in sinus rhythm at 12 months, compared with 21% (3/14) of patients treated with a mitral valve replacement alone (p < 0.05). One non-randomised controlled trial reported that 81% (83/102) of patients treated with atrial RFA and cardiac surgery were in sinus rhythm at a mean follow-up of 12.5 months, compared with 11% (3/27) of patients who had cardiac surgery without RFA (p < 0.0001). For more details, refer to the Sources of evidence. The Specialist Advisors considered this procedure to be a variation on the Cox maze technique. # Safety This procedure is performed during open heart surgery; therefore it is difficult to differentiate the complications that relate specifically to RFA. In-hospital mortality was reported by six studies, and ranged from 0.8% (1/132) to 8% (3/40). In a study of 103 patients, one death was reported to be the result of an oesophageal perforation caused by RFA. Another study noted that none of the peri-operative deaths was considered to be related to the use of RFA. Two studies reported that 2% (3/132) and 8% (18/234) of patients needed re-exploration for bleeding. Two studies reported that 0.8% (2/234) and 8% (16/200) of patients required re-operation. Other less common complications included the need for an intra-aortic balloon pump, sternal wound infection, stroke, atrio-oesophageal perforation and left atrial thrombus. For more details, refer to the Sources of evidence. The Specialist Advisors listed the potential adverse effects of RFA as oesophageal injury, heart block, perforation of the heart and coronary artery damage. # Other comments Most of the data were on patients having mitral valve surgery. There was only limited evidence on the efficacy of RFA when performed with other procedures such as coronary artery bypass grafting. This procedure appears to be more efficacious in patients whose atrial fibrillation has been of short duration (less than 1 year). It was noted that there are variations in technique and radiofrequency energy settings used for this procedure. It was also noted that it may be difficult to determine when full-thickness ablation has been achieved.# Further information NICE has published interventional procedures guidance on microwave ablation for atrial fibrillation and cryoablation for atrial fibrillation. NICE is also currently developing a guideline for the diagnosis and treatment of atrial fibrillation . NICE has recently been notified of radiofrequency catheter ablation for atrial fibrillation . # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Interventional procedure overview of radiofrequency ablation for atrial fibrillation in association with other cardiac surgery, July 2004. # Information for patients NICE has produced information on this procedure for the patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': 'Current evidence on the safety and efficacy of radiofrequency ablation (RFA) for atrial fibrillation in association with other cardiac surgery appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nPatient selection and follow-up should be carried out by a multidisciplinary team. Cardiac surgeons undertaking this procedure should have specific training in the use of radiofrequency equipment.', 'The procedure': '# Indications\n\nAtrial fibrillation is the irregular and rapid beating of the upper two chambers of the heart (the atria). It may be classified as paroxysmal, persistent or permanent. It is the most common type of arrhythmia and the incidence increases markedly with age. Patients with atrial fibrillation may be asymptomatic or they may have symptoms such as palpitations, dizziness and breathlessness. They also have an increased risk of stroke as a result of blood clots forming in the left atrium and then embolising to the brain.\n\nAtrial fibrillation usually occurs in the absence of structural heart disease. However, if structural heart disease is present, it is most commonly mitral stenosis.\n\nConservative treatments include medication, electrical cardioversion to control the heart rhythm, and anticoagulants to prevent the formation of blood clots. The conventional surgical approach, known as the Cox maze procedure, involves making multiple, strategically placed incisions in both atria to isolate and stop the abnormal electrical impulses. Alternative methods of creating lesions in the atria by ablation have been developed, using energy sources such as microwave, cryotherapy and ultrasound.\n\n# Outline of the procedure\n\nRadiofrequency ablation (RFA) for atrial fibrillation is typically carried out in patients undergoing concomitant open heart surgery (often mitral valve replacement or repair). The procedure uses thermal damage, rather than incisions, to block impulse conduction. The heat generated coagulates the heart tissue, forming linear scars or lesions that disrupt the transmission of the abnormal electrical impulses. The procedure may be carried out on both atria or on the left atrium only. It can be performed from within or outside the atrium.\n\n# Efficacy\n\nIn one small randomised controlled trial, 82% (9/11) of patients treated with atrial RFA and a mitral valve replacement were in sinus rhythm at 12 months, compared with 21% (3/14) of patients treated with a mitral valve replacement alone (p < 0.05). One non-randomised controlled trial reported that 81% (83/102) of patients treated with atrial RFA and cardiac surgery were in sinus rhythm at a mean follow-up of 12.5 months, compared with 11% (3/27) of patients who had cardiac surgery without RFA (p < 0.0001). For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors considered this procedure to be a variation on the Cox maze technique.\n\n# Safety\n\nThis procedure is performed during open heart surgery; therefore it is difficult to differentiate the complications that relate specifically to RFA.\n\nIn-hospital mortality was reported by six studies, and ranged from 0.8% (1/132) to 8% (3/40). In a study of 103 patients, one death was reported to be the result of an oesophageal perforation caused by RFA. Another study noted that none of the peri-operative deaths was considered to be related to the use of RFA.\n\nTwo studies reported that 2% (3/132) and 8% (18/234) of patients needed re-exploration for bleeding. Two studies reported that 0.8% (2/234) and 8% (16/200) of patients required re-operation. Other less common complications included the need for an intra-aortic balloon pump, sternal wound infection, stroke, atrio-oesophageal perforation and left atrial thrombus. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors listed the potential adverse effects of RFA as oesophageal injury, heart block, perforation of the heart and coronary artery damage.\n\n# Other comments\n\nMost of the data were on patients having mitral valve surgery. There was only limited evidence on the efficacy of RFA when performed with other procedures such as coronary artery bypass grafting.\n\nThis procedure appears to be more efficacious in patients whose atrial fibrillation has been of short duration (less than 1 year).\n\nIt was noted that there are variations in technique and radiofrequency energy settings used for this procedure. It was also noted that it may be difficult to determine when full-thickness ablation has been achieved.', 'Further information': 'NICE has published interventional procedures guidance on microwave ablation for atrial fibrillation and cryoablation for atrial fibrillation. NICE is also currently developing a guideline for the diagnosis and treatment of atrial fibrillation [now published as Atrial fibrillation: diagnosis and management].\n\nNICE has recently been notified of radiofrequency catheter ablation for atrial fibrillation [guidance now published as Percutaneous radiofrequency catheter ablation for atrial fibrillation].\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nInterventional procedure overview of radiofrequency ablation for atrial fibrillation in association with other cardiac surgery, July 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for the patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg121
5efe7d0a263f6453b260f4e7875762c2a9aece9e	nice	Guidance on the use of paclitaxel in the treatment of ovarian cancer	Guidance on the use of paclitaxel in the treatment of ovarian cancer Evidence-based recommendations on paclitaxel for treating ovarian cancer in adults. # Guidance This guidance replaces 'Ovarian cancer – taxanes' (NICE Technology Appraisal Guidance No 3) issued in May 2000. This guidance has been partially updated by 'Paclitaxel, pegylated liposomal doxorubicin hydrochloride and topotecan for second-line or subsequent treatment of advanced ovarian cancer (review)' (NICE technology appraisal guidance 91 ). The recommendations that have been updated are indicated in section 1 below. It is recommended that paclitaxel in combination with a platinum-based compound or platinum-based therapy alone (cisplatin or carboplatin) are offered as alternatives for first-line chemotherapy (usually following surgery) in the treatment of ovarian cancer. The choice of treatment for first-line chemotherapy for ovarian cancer should be made after discussion between the responsible clinician and the patient about the risks and benefits of the options available. In choosing between treatment with a platinum-based compound alone or paclitaxel in combination with a platinum-based compound, this discussion should cover the side-effect profiles of the alternative therapies, the stage of the woman's disease, the extent of surgical treatment of the tumour, and disease-related performance status. Recommendations 1.3, 1.4 and 1.5 have been updated and replaced by NICE technology appraisal guidance 91.# Clinical need and practice Ovarian cancer is a significant cause of early death, resulting in approximately 5000 deaths in the UK each year. Early stages of the disease are often asymptomatic, and as a result most women are diagnosed with advanced disease. This gives a relatively poor prognosis, and 5-year survival rates are reported to be around 30% in the UK and up to 40% in some European countries. Surgery is usually the first intervention used to treat the disease. However, in most women it is not possible to remove the tumour completely. Radiotherapy is usually of limited effectiveness and has side-effects on other abdominal organs. Platinum-based chemotherapy has been the established therapy in ovarian cancer for some time. However, as research evidence emerged, paclitaxel (Taxol) was added in combination with platinum. It is estimated that 75% of women with ovarian cancer currently receive a paclitaxel/platinum combination as first-line therapy. Although most patients (70% to 80%) initially respond to first-line chemotherapy, most responders eventually relapse (55% to 75% within 2 years). Responses can occur when first-line chemotherapy is repeated for a second and sometimes a third time, although they occur proportionately less frequently and do not last as long. A complete response is defined as malignant disease not detectable for at least 4 weeks, and a partial response is defined as tumour size reduced by at least 50% for more than 4 weeks. Women who initially respond to first-line therapy are also more likely to respond to second and subsequent courses of therapy. The two factors shown to be predictive of second and subsequent response to first-line therapy are the length of the progression-free interval and the extent of the relapse (that is the number of tumour sites involved and their volume). Current best practice for women who initially respond to first-line therapy is to give second and possibly subsequent courses of the same treatment at some point. Once re-treatment with first-line therapies has failed, second-line therapies can be offered. These may alleviate symptoms, but may also prolong survival. At the same time, however, they are likely to have a different range of adverse effects. Seven chemotherapy agents are licensed for second-line treatment of ovarian cancer: paclitaxel, carboplatin, chlorambucil, treosulfan, hexamethylmelamine (altretamine), topetecan, and pegylated liposomal doxorubicin hydrochloride (PLDH). Choice of second-line therapy is influenced by the effectiveness of the different agents and the patient's response to first-line therapy regimens. In May 2000, the National Institute for Clinical Excellence issued the following guidance. Paclitaxel in combination with a platinum-based therapy (cisplatin or carboplatin) should be the standard initial therapy for patients with ovarian cancer following surgery. The use of paclitaxel/platinum combination therapy in the treatment of recurrent (or resistant) ovarian cancer is recommended if the patient has not previously received this drug combination. If the patient has already received both drugs, the combination of paclitaxel and platinumbased therapy in recurrent (or resistant) ovarian cancer is not recommended, outside the context of clinical trials.It was recommended that the NICE guidance should be reviewed once full results from a further study (ICON3) were available. The present document has been prepared as part of that review.# The technology Paclitaxel (Taxol) is a cytotoxic anticancer drug and belongs to the taxane group of drugs. It has the following licensed indications for ovarian cancer in the UK: primary ovarian cancer in combination with cisplatin (a platinum drug) in patients with advanced disease or residual disease after initial surgical treatment metastatic ovarian cancer where standard platinum-containing therapy (cisplatin or carboplatin) has failed (that is, paclitaxel as monotherapy). Paclitaxel is usually administered at a dose of 175 mg per m2 body surface area, in a 3-hour intravenous infusion, followed by a platinum compound, at 3-weekly intervals. The paclitaxel infusion is usually undertaken on an outpatient basis, with drug costs of approximately £1100 per cycle. Patients normally receive six cycles, with a total drug cost of approximately £6600, excluding costs of platinum drugs, pre-medication, wider outpatient or inpatient care, the cost of treating side effects, and value added tax (VAT). While paclitaxel is licensed in combination with cisplatin for first-line therapy, both carboplatin and cisplatin are licensed for monotherapy in ovarian cancer and there is good evidence of their equivalent efficacy. However, carboplatin is recognised as being less toxic and resulting in fewer side effects. Consequently in UK clinical practice, paclitaxel is usually provided in combination with carboplatin.# Evidence The Appraisal Committee reviewed the evidence from a number of sources (Appendix B). # Clinical effectiveness ## First-line treatment Four randomised controlled trials (RCTs) provide the main evidence base for the consideration of paclitaxel as first-line therapy in ovarian cancer. Full results from the ICON3 trial and updated results from two others (GOG111, OV10) have become available since NICE issued its last guidance on the use of paclitaxel in the treatment of ovarian cancer. The GOG111 trial compared combination treatments of paclitaxel (135 mg/m2)/cisplatin (75 mg/m2) and cisplatin (75 mg/m2)/cyclophosphamide (750 mg/m2) in 410 women. All had severe disease (as defined by the International Federation of Gynaecology staging system, FIGO stage III or IV) and sub-optimal tumour reduction following surgery. No statistically significant difference in overall tumour response (that is, complete and partial response) was found (relative risk = 1.19, 95% CI = 0.95 to 1.5). However, median progression-free survival was statistically significantly longer for patients receiving the paclitaxel/cisplatin combination (18 months vs 13 months, relative risk = 0.7, 95% confidence interval = 0.5 to 0.8, p value < 0.001). Overall survival was also statistically significantly longer in these patients (38 months vs 24 months, relative risk = 0.6, 95% CI = 0.5 to 0.8, p < 0.001). Estimates from updated longer-term study results suggest that the death rate is 30% less among those treated with the paclitaxel-containing regimen (relative hazard: 0.7, 95% CI = 0.57 to 0.87). No statistically significant difference in performance scores was found between the two groups. The OV10 trial also compared the combinations of paclitaxel (175 mg/m2)/cisplatin (75 mg/m2) and cisplatin (75 mg/m2)/cyclophosphamide (750 mg/m2). The 680 women had optimal or sub-optimal tumour reduction following surgery, and 93% had FIGO stage III or IV disease. A statistically significant difference in overall tumour response (that is, complete and partial response) in favour of the paclitaxel combination was found (relative risk = 1.92, 95% CI = 1.52 to 2.42). Like GOG111, the study also found statistically significantly longer median progression-free survival for the paclitaxel combination (15.3 months vs 11.5 months, hazard ratio = 0.74, 95% CI = 0.63 to 0.88, p value = 0.0005). Overall survival was also statistically significantly higher in this group (35.6 months vs 25.8 months, hazard ratio = 0.73, 95% CI = 0.60 to 0.89, p value = 0.0016). The GOG132 trial included comparison of combination paclitaxel (135 mg/m2)/cisplatin (75 mg/m2) with cisplatin (100 mg/m2) alone. All 424 women had FIGO stage III or IV disease and sub-optimal tumour reduction following surgery. No statistically significant difference in overall tumour response (that is, complete and partial response) was found between the group receiving cisplatin alone and those receiving the paclitaxel/cisplatin combination (relative risk = 0.97, 95% CI = 0.86 to 1.09). However, unlike GOG111 and OV10, no statistically significant differences were found in progression-free survival (14.1 months vs 16.4 months, hazard ratio = 1.06, 95% CI = 0.86 to 1.30), and overall survival (26.6 months vs 30.2 months, hazard ratio = 0.99, 95% CI = 0.80 to 1.23). The difference between the findings of the trial and those reported for the GOG111 and OV10 studies may be explained by the extent of patient cross-over between treatments before the disease progressed. However it is unlikely that this is sufficient to explain such markedly different findings. The most recent trial, ICON3, compared a different combination of paclitaxel (175 mg/m2)/carboplatin (5 AUC) with either carboplatin (5 AUC) alone or a combination of cyclophosphamide (750 mg/m2)/doxorubicin (75 mg/m2)/cisplatin (75 mg/m2) (CAP). The trial differs from the others, in that patients had a wider range of residual tumour following surgery (54% had optimally reduced tumours), and a smaller proportion (80%) had FIGO stage III and IV disease. Of the total 2074 women recruited, 1421 were randomised to receive the paclitaxel/carboplatin combination or carboplatin alone. The findings of the ICON3 trial after more than 3 years' follow-up also differ from those of the GOG111 and OV10 studies. No statistically significant difference was found between the groups receiving the paclitaxel/platinum combination or carboplatin alone, in terms of progression-free survival (17.1 months vs 16.1 months, hazard ratio = 0.94, 95% CI = 0.84 to 1.05, p value = 0.24) or overall survival (37.6 months vs 36.1 months, hazard ratio = 0.96, 95% CI = 0.84 to 1.09, p value = 0.53). Also, no statistically significant differences were found in anxiety and depression scores. It is possible that the recruitment of more patients with less severe disease could have diluted the effect of paclitaxel treatment, but sub-group analyses by FIGO stage and extent of residual tumour did not show any trend supporting this. The trial design allowed choice of the control arm before randomisation, and although some suggest that this could also have diluted any treatment effect, it may be that this may better reflect clinical practice in some respects. The four trials showed consistently that treatment with paclitaxel in combination with platinum leads to more side effects. Over the four trials statistically significantly higher rates of neutropenia, allergic reactions, cardiovascular problems, hypersensitivity, neuromotor and neurosensory problems, fever and alopecia were reported in patients receiving the paclitaxel/carboplatin combination compared with the control treatments. While design differences between the four trials, in terms of severity of disease of included patients, differences in treatment and control drugs and doses, length of follow-up, and the extent of cross-over (before and after disease progression), may hamper statistical pooling of results, meta-analyses have been undertaken by the Medical Research Council (MRC) and Bristol-Myers Squibb (BMS). These take account of statistical heterogeneity as far as possible, and their results appear consistent, reporting that the findings for progression-free survival (hazard ratios = 0.84, 95% CI = 0.70 to 1.02 and 0.87, 95% CI 0.72 to 1.05 ) and overall survival (hazard ratios = 0.82, 95% CI 0.66 to 1.01 and 0.82, 95% CI 0.68 to 1.00 ) across the trials do not show statistically significant differences between paclitaxel/platinum and the alternatives. ## Second-line treatment Four published RCTs on the second-line use of paclitaxel (monotherapy) in the treatment of ovarian cancer were identified. However, two of these studies compared paclitaxel with unlicensed treatments, and one compared different dosing schedules of paclitaxel itself. In the remaining RCT, paclitaxel was compared with topotecan in 235 women who had been previously treated with a platinum-based compound (they had not been previously treated with paclitaxel). The trial found no statistically significant differences in overall tumour response, progression-free survival or overall survival. The incidence of neutropenia, anaemia, thrombocytopenia, leukopenia, nausea and vomiting was significantly lower among patients receiving paclitaxel than among those receiving topotecan. However, there was a significantly higher incidence of alopecia among the paclitaxel-treated group. # Cost effectiveness Eleven cost-effectiveness analyses and three cost–utility analyses were available as evidence on the first-line use of paclitaxel. All were based on trials favouring paclitaxel (that is, GOG111 or OV10), and therefore found the paclitaxel/platinum combination to be more costly and more effective than control treatments. Three of the analyses could be directly applied to the UK. Two published UK cost-effectiveness analyses found that the incremental cost per life-year gained for paclitaxel/platinum ranged between £7173 and £12,417, depending on the effectiveness trial results and drug doses applied. One of the studies reported the incremental cost per progression-free life-year gained to be between £20,084 and £22,021, again depending on the trial results applied. One published UK cost–utility analysis was available, but its methods were not well reported, and its results need to be interpreted with caution. An incremental cost–utility estimate based on this analysis, for paclitaxel/platinum compared with carboplatin alone, showed the incremental cost per quality-adjusted life year to be £5273. A cost-effectiveness analysis undertaken by the manufacturer of paclitaxel was also available. The analysis was based on resource use and outcomes from GOG111, though carboplatin was substituted as the control treatment, as this better reflects UK practice. Consequently the analysis assumed equivalent efficacy between carboplatin and cisplatin in combination with paclitaxel. UK unit costs were incorporated from routine sources, and included: chemotherapy drugs, pre-medication, drug administration, management of febrile neutropenia, and other inpatient and outpatient care. For the paclitaxel/carboplatin combination vs carboplatin alone, the analysis reported an incremental cost of £7074 per life-year gained and £10,808 per progression-free life-year gained. Given that this analysis was based on the survival in the most favourable survival findings available (that is, a hazard ratio of 0.61 in favour of paclitaxel/platinum combination for overall survival), sensitivity analyses were undertaken by NICE to indicate the likely magnitude of effect on the cost-effectiveness ratio of changing the survival gains attributed to paclitaxel/platinum. Simply adjusting the manufacturer's analysis to the survival difference reported by ICON3 (hazard ratio of 0.96) suggests an incremental cost per life-year gained in the region of £45,000. However, other analyses undertaken by NICE suggest that the cost per life-year gained could be much higher. # Consideration of the evidence Having carefully considered the design and full findings of ICON3 in conjunction with the three other published (updated) RCTs, the Committee concluded that all of the trials contribute to the understanding of the clinical effectiveness of paclitaxel in the first-line treatment of ovarian cancer. The Committee noted that the availability of the full ICON3 evidence meant that two of the four published trials favoured paclitaxel in combination with a platinum-based compound, whereas two trials failed to show a significant difference in survival between the combination and a platinum-based compound alone. The combination of these findings in meta-analyses suggested that there was no statistically significant survival advantage for one of these therapeutic approaches over the other. In addition, cost-effectiveness estimates varied considerably with the assumed magnitude of the survival difference. The Committee took account of this range of trial evidence as well as other factors that would differentiate between the two regimens including the side-effect profiles of the treatments, and the broad range of cost-effectiveness estimates presented. On this basis the Committee considered that paclitaxel/platinum combination treatment should no longer be recommended exclusively as standard therapy for women receiving first-line chemotherapy for ovarian cancer. As a consequence the Committee considered that both platinum therapy alone and a combination of paclitaxel and a platinum compound were appropriate first-line treatments for women with ovarian cancer. The Committee discussed pathways of care for women with ovarian cancer. It was recognised that women with a good initial response to first-line therapy will be offered additional courses of the chosen treatment, and will be offered second-line treatment options once the tumour fails to respond to the chosen first-line regimen. In view of the limited evidence available on the clinical effectiveness of paclitaxel in second-line treatment, the Committee concluded that paclitaxel should be considered as an option for second-line treatment only for women who do not receive it as part of their first-line therapy. For such women, it should be offered as one option alongside other drugs that are licensed for second-line treatment of ovarian cancer.# Implications for the NHS In May 2000 the Institute's guidance indicated that the total annual cost of adding paclitaxel to platinum therapy in England and Wales was approximately £28 million (assuming that 4000 patients were treated at a cost of £7000 each). Given that the guidance set out in Section 1 promotes informed choice between the available treatments, it is difficult to estimate the likely current resource impact on the NHS. However it appears unlikely that the guidance will result in an increase in the resources required to treat ovarian cancer. In fact, since women who do not receive paclitaxel in combination as first-line chemotherapy may receive the drug later as second-line therapy, the total number receiving paclitaxel at some point in their treatment may remain approximately unchanged, as may the total cost of chemotherapy for ovarian cancer.# Further research Research would be beneficial to examine the following aspects of effectiveness and cost effectiveness of paclitaxel: whether paclitaxel/platinum combination therapy is of particular benefit to identifiable clinical sub-groups the optimal sequencing of paclitaxel therapy with other ovarian chemotherapy compounds – that is paclitaxel/ platinum combination vs platinum followed by paclitaxel in sequence.# Related guidance In August 2001, NICE issued the guidance on topotecan: National Institute for Clinical Excellence (2001), Guidance on the use of topotecan for the treatment of ovarian cancer. NICE Technology Appraisal Guidance No.28. London: National Institute for Clinical Excellence. Available from www.nice.org.uk In July 2002, NICE issued guidance on the use of PLDH in ovarian cancer: National Institute for Clinical Excellence (2002), Guidance on the use of pegylated liposomal doxorubicin hydrochloride in the treatment of advanced ovarian cancer. NICE Technology Appraisal Guidance No. 45. London: National Institute for Clinical Excellence. Available from www.nice.org.uk.# Review of guidance The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated assessment report, and decide whether the technology should be referred to the Appraisal Committee for review. It is planned that a review of this technology, along with topotecan and PLDH, will start in July 2003 and will take into account all new evidence. Andrew DillonChief ExecutiveJanuary 2003# Appendix C. Patient information. Guidance on the use of paclitaxel in the treatment of ovarian cancer A summary for patients and carers can be found on the NICE website.# Appendix D. Detail on criteria for audit of the use of paclitaxel in the treatment of women with ovarian cancer # Possible objectives for an audit An audit on the treatment of ovarian cancer could be carried out to ensure that: paclitaxel is used appropriately women with ovarian cancer participate in making the choice concerning their therapy chemotherapy for women with ovarian cancer is supervised by an appropriate specialist. # Patients to be included in an audit All women undergoing treatment for ovarian cancer over a reasonable time period, for example, 1 year. For measures 3 and 4 below, it may be useful to include women who were diagnosed and begun on chemotherapy sufficiently long ago that relapses and second-line therapy may have occurred. # Measures that can be used as a basis for audit The measures that can be used in an audit are as follows: Criterion Standard Exception Definition of Terms . Paclitaxel in combination with a platinum-based compound or platinum-based therapy alone is offered for first-line chemotherapy % of women with ovarian cancer A. None First-line = usually following surgery. Platinum-based compound = cisplatin or carboplatin . The choice of treatment for first-line chemotherapy is based on discussion between the patient and the responsible clinician % of women with ovarian cancer None Local specialists should agree on how discussion with the woman about the risks and benefits of the options available is documented, for audit purposes. Reference should be made to side-effect profiles of the alternative therapies, the stage of the woman's disease, the extent of surgical treatment of the tumour, and disease-related performance status . Additional courses of treatment with the chosen chemotherapy regimen are offered to women following relapse after initial (or subsequent) courses of first-line chemotherapy, if the extent and duration of the initial response is adequate % of women with ovarian cancer who received first-line chemotherapy and who have experienced a relapse A. Inadequate or too short a duration of initial response B. The woman declines treatment following discussion with the responsible clinician Local specialists should agree on how to judge the adequacy and duration of initial response, for audit purposes . Paclitaxel is considered as second-line (or subsequent) treatment % of women with ovarian cancer A. The woman has not received paclitaxel previously as part of first-line treatment . The provision of chemotherapy is supervised by an oncologist specialising in ovarian cancer % of women with ovarian cancer None Local specialists should agree on what constitutes supervision, for audit purposes ## Calculation of compliance with the measures Compliance with the measure described in the table is calculated as follows. Number of patients whose care is consistent with the criterion plus the number meeting any applicable exceptions Number of patients in the audit to which the Criterion and Exception(s), where applicable, apply X 100 Clinicians should review the findings of measurement, identify if practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that desired improvement is being achieved.# Changes after publication March 2014: implementation section updated to clarify that paclitaxel is recommended as an option for treating ovarian cancer. Additional minor maintenance update also carried out. March 2012: minor maintenance This guidance has been partially updated by 'Paclitaxel, pegylated liposomal doxorubicin hydrochloride and topotecan for second-line or subsequent treatment of advanced ovarian cancer (review)' (NICE technology appraisal guidance 91 . Recommendations 1.3, 1.4 and 1.5 on re-challenge therapy and the second-line treatment of advanced ovarian cancer have been replaced. The recommendations for first-line treatment still stand. See TA91 for details of the new recommendations and evidence considered.# About this guidance NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales. This guidance was developed using the NICE single technology appraisal process. It replaces 'Ovarian cancer – taxanes' (NICE Technology Appraisal Guidance No 3) issued in May 2000. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2003. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.	{'Guidance': "This guidance replaces 'Ovarian cancer – taxanes' (NICE Technology Appraisal Guidance No 3) issued in May 2000.\n\nThis guidance has been partially updated by 'Paclitaxel, pegylated liposomal doxorubicin hydrochloride and topotecan for second-line or subsequent treatment of advanced ovarian cancer (review)' (NICE technology appraisal guidance 91 [TA91]). The recommendations that have been updated are indicated in section 1 below.\n\nIt is recommended that paclitaxel in combination with a platinum-based compound or platinum-based therapy alone (cisplatin or carboplatin) are offered as alternatives for first-line chemotherapy (usually following surgery) in the treatment of ovarian cancer.\n\nThe choice of treatment for first-line chemotherapy for ovarian cancer should be made after discussion between the responsible clinician and the patient about the risks and benefits of the options available. In choosing between treatment with a platinum-based compound alone or paclitaxel in combination with a platinum-based compound, this discussion should cover the side-effect profiles of the alternative therapies, the stage of the woman's disease, the extent of surgical treatment of the tumour, and disease-related performance status.\n\nRecommendations 1.3, 1.4 and 1.5 have been updated and replaced by NICE technology appraisal guidance 91.", 'Clinical need and practice': "Ovarian cancer is a significant cause of early death, resulting in approximately 5000 deaths in the UK each year.\n\nEarly stages of the disease are often asymptomatic, and as a result most women are diagnosed with advanced disease. This gives a relatively poor prognosis, and 5-year survival rates are reported to be around 30% in the UK and up to 40% in some European countries.\n\nSurgery is usually the first intervention used to treat the disease. However, in most women it is not possible to remove the tumour completely. Radiotherapy is usually of limited effectiveness and has side-effects on other abdominal organs.\n\nPlatinum-based chemotherapy has been the established therapy in ovarian cancer for some time. However, as research evidence emerged, paclitaxel (Taxol) was added in combination with platinum. It is estimated that 75% of women with ovarian cancer currently receive a paclitaxel/platinum combination as first-line therapy.\n\nAlthough most patients (70% to 80%) initially respond to first-line chemotherapy, most responders eventually relapse (55% to 75% within 2 years). Responses can occur when first-line chemotherapy is repeated for a second and sometimes a third time, although they occur proportionately less frequently and do not last as long. A complete response is defined as malignant disease not detectable for at least 4 weeks, and a partial response is defined as tumour size reduced by at least 50% for more than 4 weeks.\n\nWomen who initially respond to first-line therapy are also more likely to respond to second and subsequent courses of therapy. The two factors shown to be predictive of second and subsequent response to first-line therapy are the length of the progression-free interval and the extent of the relapse (that is the number of tumour sites involved and their volume). Current best practice for women who initially respond to first-line therapy is to give second and possibly subsequent courses of the same treatment at some point.\n\nOnce re-treatment with first-line therapies has failed, second-line therapies can be offered. These may alleviate symptoms, but may also prolong survival. At the same time, however, they are likely to have a different range of adverse effects.\n\nSeven chemotherapy agents are licensed for second-line treatment of ovarian cancer: paclitaxel, carboplatin, chlorambucil, treosulfan, hexamethylmelamine (altretamine), topetecan, and pegylated liposomal doxorubicin hydrochloride (PLDH).\n\nChoice of second-line therapy is influenced by the effectiveness of the different agents and the patient's response to first-line therapy regimens.\n\nIn May 2000, the National Institute for Clinical Excellence issued the following guidance.\n\nPaclitaxel in combination with a platinum-based therapy (cisplatin or carboplatin) should be the standard initial therapy for patients with ovarian cancer following surgery.\n\nThe use of paclitaxel/platinum combination therapy in the treatment of recurrent (or resistant) ovarian cancer is recommended if the patient has not previously received this drug combination. If the patient has already received both drugs, the combination of paclitaxel and platinumbased therapy in recurrent (or resistant) ovarian cancer is not recommended, outside the context of clinical trials.It was recommended that the NICE guidance should be reviewed once full results from a further study (ICON3) were available. The present document has been prepared as part of that review.", 'The technology': 'Paclitaxel (Taxol) is a cytotoxic anticancer drug and belongs to the taxane group of drugs. It has the following licensed indications for ovarian cancer in the UK:\n\nprimary ovarian cancer in combination with cisplatin (a platinum drug) in patients with advanced disease or residual disease after initial surgical treatment\n\nmetastatic ovarian cancer where standard platinum-containing therapy (cisplatin or carboplatin) has failed (that is, paclitaxel as monotherapy).\n\nPaclitaxel is usually administered at a dose of 175 mg per m2 body surface area, in a 3-hour intravenous infusion, followed by a platinum compound, at 3-weekly intervals. The paclitaxel infusion is usually undertaken on an outpatient basis, with drug costs of approximately £1100 per cycle. Patients normally receive six cycles, with a total drug cost of approximately £6600, excluding costs of platinum drugs, pre-medication, wider outpatient or inpatient care, the cost of treating side effects, and value added tax (VAT).\n\nWhile paclitaxel is licensed in combination with cisplatin for first-line therapy, both carboplatin and cisplatin are licensed for monotherapy in ovarian cancer and there is good evidence of their equivalent efficacy. However, carboplatin is recognised as being less toxic and resulting in fewer side effects. Consequently in UK clinical practice, paclitaxel is usually provided in combination with carboplatin.', 'Evidence ': "The Appraisal Committee reviewed the evidence from a number of sources (Appendix B).\n\n# Clinical effectiveness\n\n## First-line treatment\n\nFour randomised controlled trials (RCTs) provide the main evidence base for the consideration of paclitaxel as first-line therapy in ovarian cancer. Full results from the ICON3 trial and updated results from two others (GOG111, OV10) have become available since NICE issued its last guidance on the use of paclitaxel in the treatment of ovarian cancer.\n\nThe GOG111 trial compared combination treatments of paclitaxel (135 mg/m2)/cisplatin (75 mg/m2) and cisplatin (75 mg/m2)/cyclophosphamide (750 mg/m2) in 410 women. All had severe disease (as defined by the International Federation of Gynaecology staging system, FIGO stage III or IV) and sub-optimal tumour reduction following surgery. No statistically significant difference in overall tumour response (that is, complete and partial response) was found (relative risk = 1.19, 95% CI = 0.95 to 1.5). However, median progression-free survival was statistically significantly longer for patients receiving the paclitaxel/cisplatin combination (18 months vs 13 months, relative risk = 0.7, 95% confidence interval [CI] = 0.5 to 0.8, p value < 0.001). Overall survival was also statistically significantly longer in these patients (38 months vs 24 months, relative risk = 0.6, 95% CI = 0.5 to 0.8, p < 0.001). Estimates from updated longer-term study results suggest that the death rate is 30% less among those treated with the paclitaxel-containing regimen (relative hazard: 0.7, 95% CI = 0.57 to 0.87). No statistically significant difference in performance scores was found between the two groups.\n\nThe OV10 trial also compared the combinations of paclitaxel (175 mg/m2)/cisplatin (75 mg/m2) and cisplatin (75 mg/m2)/cyclophosphamide (750 mg/m2). The 680 women had optimal or sub-optimal tumour reduction following surgery, and 93% had FIGO stage III or IV disease. A statistically significant difference in overall tumour response (that is, complete and partial response) in favour of the paclitaxel combination was found (relative risk = 1.92, 95% CI = 1.52 to 2.42). Like GOG111, the study also found statistically significantly longer median progression-free survival for the paclitaxel combination (15.3 months vs 11.5 months, hazard ratio = 0.74, 95% CI = 0.63 to 0.88, p value = 0.0005). Overall survival was also statistically significantly higher in this group (35.6 months vs 25.8 months, hazard ratio = 0.73, 95% CI = 0.60 to 0.89, p value = 0.0016).\n\nThe GOG132 trial included comparison of combination paclitaxel (135 mg/m2)/cisplatin (75 mg/m2) with cisplatin (100 mg/m2) alone. All 424 women had FIGO stage III or IV disease and sub-optimal tumour reduction following surgery. No statistically significant difference in overall tumour response (that is, complete and partial response) was found between the group receiving cisplatin alone and those receiving the paclitaxel/cisplatin combination (relative risk = 0.97, 95% CI = 0.86 to 1.09). However, unlike GOG111 and OV10, no statistically significant differences were found in progression-free survival (14.1 months vs 16.4 months, hazard ratio = 1.06, 95% CI = 0.86 to 1.30), and overall survival (26.6 months vs 30.2 months, hazard ratio = 0.99, 95% CI = 0.80 to 1.23). The difference between the findings of the trial and those reported for the GOG111 and OV10 studies may be explained by the extent of patient cross-over between treatments before the disease progressed. However it is unlikely that this is sufficient to explain such markedly different findings.\n\nThe most recent trial, ICON3, compared a different combination of paclitaxel (175 mg/m2)/carboplatin (5 AUC) with either carboplatin (5 AUC) alone or a combination of cyclophosphamide (750 mg/m2)/doxorubicin (75 mg/m2)/cisplatin (75 mg/m2) (CAP). The trial differs from the others, in that patients had a wider range of residual tumour following surgery (54% had optimally reduced tumours), and a smaller proportion (80%) had FIGO stage III and IV disease. Of the total 2074 women recruited, 1421 were randomised to receive the paclitaxel/carboplatin combination or carboplatin alone. The findings of the ICON3 trial after more than 3 years' follow-up also differ from those of the GOG111 and OV10 studies. No statistically significant difference was found between the groups receiving the paclitaxel/platinum combination or carboplatin alone, in terms of progression-free survival (17.1 months vs 16.1 months, hazard ratio = 0.94, 95% CI = 0.84 to 1.05, p value = 0.24) or overall survival (37.6 months vs 36.1 months, hazard ratio = 0.96, 95% CI = 0.84 to 1.09, p value = 0.53). Also, no statistically significant differences were found in anxiety and depression scores. It is possible that the recruitment of more patients with less severe disease could have diluted the effect of paclitaxel treatment, but sub-group analyses by FIGO stage and extent of residual tumour did not show any trend supporting this. The trial design allowed choice of the control arm before randomisation, and although some suggest that this could also have diluted any treatment effect, it may be that this may better reflect clinical practice in some respects.\n\nThe four trials showed consistently that treatment with paclitaxel in combination with platinum leads to more side effects. Over the four trials statistically significantly higher rates of neutropenia, allergic reactions, cardiovascular problems, hypersensitivity, neuromotor and neurosensory problems, fever and alopecia were reported in patients receiving the paclitaxel/carboplatin combination compared with the control treatments.\n\nWhile design differences between the four trials, in terms of severity of disease of included patients, differences in treatment and control drugs and doses, length of follow-up, and the extent of cross-over (before and after disease progression), may hamper statistical pooling of results, meta-analyses have been undertaken by the Medical Research Council (MRC) and Bristol-Myers Squibb (BMS). These take account of statistical heterogeneity as far as possible, and their results appear consistent, reporting that the findings for progression-free survival (hazard ratios = 0.84, 95% CI = 0.70 to 1.02 [MRC] and 0.87, 95% CI 0.72 to 1.05 [BMS]) and overall survival (hazard ratios = 0.82, 95% CI 0.66 to 1.01 [MRC] and 0.82, 95% CI 0.68 to 1.00 [BMS]) across the trials do not show statistically significant differences between paclitaxel/platinum and the alternatives.\n\n## Second-line treatment\n\nFour published RCTs on the second-line use of paclitaxel (monotherapy) in the treatment of ovarian cancer were identified. However, two of these studies compared paclitaxel with unlicensed treatments, and one compared different dosing schedules of paclitaxel itself.\n\nIn the remaining RCT, paclitaxel was compared with topotecan in 235 women who had been previously treated with a platinum-based compound (they had not been previously treated with paclitaxel). The trial found no statistically significant differences in overall tumour response, progression-free survival or overall survival. The incidence of neutropenia, anaemia, thrombocytopenia, leukopenia, nausea and vomiting was significantly lower among patients receiving paclitaxel than among those receiving topotecan. However, there was a significantly higher incidence of alopecia among the paclitaxel-treated group.\n\n# Cost effectiveness\n\nEleven cost-effectiveness analyses and three cost–utility analyses were available as evidence on the first-line use of paclitaxel. All were based on trials favouring paclitaxel (that is, GOG111 or OV10), and therefore found the paclitaxel/platinum combination to be more costly and more effective than control treatments. Three of the analyses could be directly applied to the UK.\n\nTwo published UK cost-effectiveness analyses found that the incremental cost per life-year gained for paclitaxel/platinum ranged between £7173 and £12,417, depending on the effectiveness trial results and drug doses applied. One of the studies reported the incremental cost per progression-free life-year gained to be between £20,084 and £22,021, again depending on the trial results applied.\n\nOne published UK cost–utility analysis was available, but its methods were not well reported, and its results need to be interpreted with caution. An incremental cost–utility estimate based on this analysis, for paclitaxel/platinum compared with carboplatin alone, showed the incremental cost per quality-adjusted life year to be £5273.\n\nA cost-effectiveness analysis undertaken by the manufacturer of paclitaxel was also available. The analysis was based on resource use and outcomes from GOG111, though carboplatin was substituted as the control treatment, as this better reflects UK practice. Consequently the analysis assumed equivalent efficacy between carboplatin and cisplatin in combination with paclitaxel. UK unit costs were incorporated from routine sources, and included: chemotherapy drugs, pre-medication, drug administration, management of febrile neutropenia, and other inpatient and outpatient care. For the paclitaxel/carboplatin combination vs carboplatin alone, the analysis reported an incremental cost of £7074 per life-year gained and £10,808 per progression-free life-year gained.\n\nGiven that this analysis was based on the survival in the most favourable survival findings available (that is, a hazard ratio of 0.61 in favour of paclitaxel/platinum combination for overall survival), sensitivity analyses were undertaken by NICE to indicate the likely magnitude of effect on the cost-effectiveness ratio of changing the survival gains attributed to paclitaxel/platinum. Simply adjusting the manufacturer's analysis to the survival difference reported by ICON3 (hazard ratio of 0.96) suggests an incremental cost per life-year gained in the region of £45,000. However, other analyses undertaken by NICE suggest that the cost per life-year gained could be much higher.\n\n# Consideration of the evidence\n\nHaving carefully considered the design and full findings of ICON3 in conjunction with the three other published (updated) RCTs, the Committee concluded that all of the trials contribute to the understanding of the clinical effectiveness of paclitaxel in the first-line treatment of ovarian cancer.\n\nThe Committee noted that the availability of the full ICON3 evidence meant that two of the four published trials favoured paclitaxel in combination with a platinum-based compound, whereas two trials failed to show a significant difference in survival between the combination and a platinum-based compound alone. The combination of these findings in meta-analyses suggested that there was no statistically significant survival advantage for one of these therapeutic approaches over the other. In addition, cost-effectiveness estimates varied considerably with the assumed magnitude of the survival difference.\n\nThe Committee took account of this range of trial evidence as well as other factors that would differentiate between the two regimens including the side-effect profiles of the treatments, and the broad range of cost-effectiveness estimates presented. On this basis the Committee considered that paclitaxel/platinum combination treatment should no longer be recommended exclusively as standard therapy for women receiving first-line chemotherapy for ovarian cancer. As a consequence the Committee considered that both platinum therapy alone and a combination of paclitaxel and a platinum compound were appropriate first-line treatments for women with ovarian cancer.\n\nThe Committee discussed pathways of care for women with ovarian cancer. It was recognised that women with a good initial response to first-line therapy will be offered additional courses of the chosen treatment, and will be offered second-line treatment options once the tumour fails to respond to the chosen first-line regimen.\n\nIn view of the limited evidence available on the clinical effectiveness of paclitaxel in second-line treatment, the Committee concluded that paclitaxel should be considered as an option for second-line treatment only for women who do not receive it as part of their first-line therapy. For such women, it should be offered as one option alongside other drugs that are licensed for second-line treatment of ovarian cancer.", 'Implications for the NHS': "In May 2000 the Institute's guidance indicated that the total annual cost of adding paclitaxel to platinum therapy in England and Wales was approximately £28 million (assuming that 4000 patients were treated at a cost of £7000 each).\n\nGiven that the guidance set out in Section 1 promotes informed choice between the available treatments, it is difficult to estimate the likely current resource impact on the NHS. However it appears unlikely that the guidance will result in an increase in the resources required to treat ovarian cancer. In fact, since women who do not receive paclitaxel in combination as first-line chemotherapy may receive the drug later as second-line therapy, the total number receiving paclitaxel at some point in their treatment may remain approximately unchanged, as may the total cost of chemotherapy for ovarian cancer.", 'Further research': 'Research would be beneficial to examine the following aspects of effectiveness and cost effectiveness of paclitaxel:\n\nwhether paclitaxel/platinum combination therapy is of particular benefit to identifiable clinical sub-groups\n\nthe optimal sequencing of paclitaxel therapy with other ovarian chemotherapy compounds – that is paclitaxel/ platinum combination vs platinum followed by paclitaxel in sequence.', 'Related guidance': 'In August 2001, NICE issued the guidance on topotecan: National Institute for Clinical Excellence (2001), Guidance on the use of topotecan for the treatment of ovarian cancer. NICE Technology Appraisal Guidance No.28. London: National Institute for Clinical Excellence. Available from www.nice.org.uk\n\nIn July 2002, NICE issued guidance on the use of PLDH in ovarian cancer: National Institute for Clinical Excellence (2002), Guidance on the use of pegylated liposomal doxorubicin hydrochloride in the treatment of advanced ovarian cancer. NICE Technology Appraisal Guidance No. 45. London: National Institute for Clinical Excellence. Available from www.nice.org.uk.', 'Review of guidance': 'The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated assessment report, and decide whether the technology should be referred to the Appraisal Committee for review.\n\nIt is planned that a review of this technology, along with topotecan and PLDH, will start in July 2003 and will take into account all new evidence.\n\nAndrew DillonChief ExecutiveJanuary 2003', 'Appendix C. Patient information. Guidance on the use of paclitaxel in the treatment of ovarian cancer': 'A summary for patients and carers can be found on the NICE website.', 'Appendix D. Detail on criteria for audit of the use of paclitaxel in the treatment of women with ovarian cancer': "# Possible objectives for an audit\n\nAn audit on the treatment of ovarian cancer could be carried out to ensure that:\n\npaclitaxel is used appropriately\n\nwomen with ovarian cancer participate in making the choice concerning their therapy\n\nchemotherapy for women with ovarian cancer is supervised by an appropriate specialist.\n\n# Patients to be included in an audit\n\nAll women undergoing treatment for ovarian cancer over a reasonable time period, for example, 1 year. For measures 3 and 4 below, it may be useful to include women who were diagnosed and begun on chemotherapy sufficiently long ago that relapses and second-line therapy may have occurred.\n\n# Measures that can be used as a basis for audit\n\nThe measures that can be used in an audit are as follows:\n\nCriterion\n\nStandard\n\nException\n\nDefinition of Terms\n\n. Paclitaxel in combination with a platinum-based compound or platinum-based therapy alone is offered for first-line chemotherapy\n\n% of women with ovarian cancer\n\nA. None\n\nFirst-line = usually following surgery. Platinum-based compound = cisplatin or carboplatin\n\n. The choice of treatment for first-line chemotherapy is based on discussion between the patient and the responsible clinician\n\n% of women with ovarian cancer\n\nNone\n\nLocal specialists should agree on how discussion with the woman about the risks and benefits of the options available is documented, for audit purposes. Reference should be made to side-effect profiles of the alternative therapies, the stage of the woman's disease, the extent of surgical treatment of the tumour, and disease-related performance status\n\n. Additional courses of treatment with the chosen chemotherapy regimen are offered to women following relapse after initial (or subsequent) courses of first-line chemotherapy, if the extent and duration of the initial response is adequate\n\n% of women with ovarian cancer who received first-line chemotherapy and who have experienced a relapse\n\nA. Inadequate or too short a duration of initial response\n\nB. The woman declines treatment following discussion with the responsible clinician\n\nLocal specialists should agree on how to judge the adequacy and duration of initial response, for audit purposes\n\n. Paclitaxel is considered as second-line (or subsequent) treatment\n\n% of women with ovarian cancer\n\nA. The woman has not received paclitaxel previously as part of first-line treatment\n\n\n\n. The provision of chemotherapy is supervised by an oncologist specialising in ovarian cancer\n\n% of women with ovarian cancer\n\nNone\n\nLocal specialists should agree on what constitutes supervision, for audit purposes\n\n## Calculation of compliance with the measures\n\nCompliance with the measure described in the table is calculated as follows.\n\nNumber of patients whose care is consistent with the criterion plus the number meeting any applicable exceptions\n\n/\n\nNumber of patients in the audit to which the Criterion and Exception(s), where applicable, apply\n\nX 100\n\nClinicians should review the findings of measurement, identify if practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that desired improvement is being achieved.", 'Changes after publication': "March 2014: implementation section updated to clarify that paclitaxel is recommended as an option for treating ovarian cancer. Additional minor maintenance update also carried out.\n\nMarch 2012: minor maintenance\n\nThis guidance has been partially updated by 'Paclitaxel, pegylated liposomal doxorubicin hydrochloride and topotecan for second-line or subsequent treatment of advanced ovarian cancer (review)' (NICE technology appraisal guidance 91 [TA91]. Recommendations 1.3, 1.4 and 1.5 on re-challenge therapy and the second-line treatment of advanced ovarian cancer have been replaced. The recommendations for first-line treatment still stand. See TA91 for details of the new recommendations and evidence considered.", 'About this guidance': "NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales.\n\nThis guidance was developed using the NICE single technology appraisal process.\n\nIt replaces 'Ovarian cancer – taxanes' (NICE Technology Appraisal Guidance No 3) issued in May 2000.\n\nWe have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2003. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE."}	https://www.nice.org.uk/guidance/ta55	Evidence-based recommendations on paclitaxel for treating ovarian cancer in adults.
e77febaf139712557220e964ccb96afb39e2d8bc	nice	High-intensity focused ultrasound for prostate cancer	High-intensity focused ultrasound for prostate cancer # Guidance Current evidence on the safety and efficacy of high-intensity focused ultrasound (HIFU), as measured by reduction in prostate-specific antigen (PSA) levels and biopsy findings, appears adequate to support the use of this procedure for the treatment of prostate cancer provided that the normal arrangements are in place for consent, audit and clinical governance. The effects of HIFU for prostate cancer on quality of life and long-term survival remain uncertain. Clinicians should therefore ensure that patients understand the uncertainties and the alternative treatment options. Use of NICE's information for the public is recommended. Interpretation of the data was difficult because it was not clear from the literature when the procedure was used for primary or for salvage treatment. Further research and audit should address clinical outcomes, long-term survival and indications for treatment (differentiating between the use of the procedure for primary and for salvage treatment).# The procedure # Indications High-intensity focused ultrasound (HIFU) may be used to treat carcinoma of the prostate, either as a primary or salvage therapy. Treatment options depend on the stage of the cancer. Current primary treatments for localised prostate cancer include 'watchful waiting', radiotherapy and radical prostatectomy. Metastatic prostate cancer is usually treated with hormone therapy. Treatment options for locally recurrent prostate cancer after radiotherapy are limited and include salvage radical prostatectomy, salvage cryotherapy and salvage brachytherapy. # Outline of the procedure HIFU for prostate cancer is carried out under a spinal or general anaesthesia. An endorectal probe incorporating an ultrasound scanner and a HIFU treatment applicator is inserted. The probe emits a beam of ultrasound, which is focused to reach a high intensity in the target area. Absorption of the ultrasound energy creates an increase in temperature, which destroys tissue. A cooling balloon surrounding the probe protects the rectal mucosa from the high temperature. A urethral or suprapubic catheter is used after the procedure. Transurethral resection of the prostate may be carried out immediately before the HIFU treatment, to reduce the volume of the prostate and minimise the amount of necrotic debris left after the procedure. HIFU treatment can be repeated if necessary. # Efficacy The evidence was based on case series and the main outcomes reported were negative biopsy rates and PSA nadir levels. Some studies reported disease-free survival rates but the criteria used to define disease varied. A systematic review, including eight case series, reported a negative biopsy rate of 60% (37/62) in one study with follow up not specified, and 80% (75/94) in a study with 3-year follow up. In three further studies in the review, the proportion of patients without clinical or biochemical evidence of disease ranged from 56% (28/50) at 24 months to 66% (67/102) at 19 months. Three additional case series reported negative biopsy rates between 87% (251/288) in a study with mean follow up of 13 months and 93% (128/137) in a study with mean follow up of 22.5 months. One of these studies, which included 146 patients, also reported disease-free survival rates of 54% or 71.5%, depending on the criteria used to define disease-free status. For more details, refer to the Sources of evidence section. The Specialist Advisors considered that long-term data are needed to establish whether the procedure reduces prostate-cancer-specific mortality. # Safety Urinary tract infections and stress incontinence were the most commonly reported complications, affecting between 4% (6/137) and 48% (46/96) and between 8% (9/111) and 23% (23/102) of patients in two case series. Recto-urethral fistula was reported in 0.7% (1/137) and 3% (3/111) of patients. Four studies reported rates of impotence after the procedure between 24% (75/315) and 100% (62/62) but the proportion of men who were potent before treatment was inadequately reported. Other complications included prolonged urinary retention, urge incontinence, urgency, bladder neck stenosis, urethral stenosis, urethritis, prostatic abscess, epididymitis, asymptomatic rectal burns and chronic pelvic pain. For more details, refer to the Sources of evidence section. The Specialist Advisors listed urinary incontinence, rectal fistula, bowel perforation and erectile dysfunction as potential adverse events but noted that HIFU appears to be safer than alternative radical treatments for prostate cancer. Two Specialist Advisors noted that there were concerns regarding control of local heating and limiting sound energy to the target area. # Other comments In recommending that further research and audit should address long-term survival, it is noted that prostate cancer patients frequently die from unrelated causes. Most of the evidence related to localised prostate cancer.# Other NICE recommendations on high-intensity focused ultrasound for prostate cancer Further recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008, as follows: High intensity focused ultrasound (HIFU) and cryotherapy are not recommended for men with localised prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions. Clinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available in NICE's guideline on prostate cancer diagnosis and management. The IP guidance on high-intensity focused ultrasound for prostate cancer remains current, and should be read in conjunction with the clinical guideline.# Further information NICE has issued guidance on urological cancer services, which includes prostate cancer. NICE has also issued interventional procedures guidance on laparoscopic radical prostatectomy and salvage cryotherapy for recurrent prostate cancer. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of high-intensity focused ultrasound (HIFU), as measured by reduction in prostate-specific antigen (PSA) levels and biopsy findings, appears adequate to support the use of this procedure for the treatment of prostate cancer provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe effects of HIFU for prostate cancer on quality of life and long-term survival remain uncertain. Clinicians should therefore ensure that patients understand the uncertainties and the alternative treatment options. Use of NICE's information for the public is recommended.\n\nInterpretation of the data was difficult because it was not clear from the literature when the procedure was used for primary or for salvage treatment. Further research and audit should address clinical outcomes, long-term survival and indications for treatment (differentiating between the use of the procedure for primary and for salvage treatment).", 'The procedure': "# Indications\n\nHigh-intensity focused ultrasound (HIFU) may be used to treat carcinoma of the prostate, either as a primary or salvage therapy.\n\nTreatment options depend on the stage of the cancer. Current primary treatments for localised prostate cancer include 'watchful waiting', radiotherapy and radical prostatectomy. Metastatic prostate cancer is usually treated with hormone therapy.\n\nTreatment options for locally recurrent prostate cancer after radiotherapy are limited and include salvage radical prostatectomy, salvage cryotherapy and salvage brachytherapy.\n\n# Outline of the procedure\n\nHIFU for prostate cancer is carried out under a spinal or general anaesthesia. An endorectal probe incorporating an ultrasound scanner and a HIFU treatment applicator is inserted. The probe emits a beam of ultrasound, which is focused to reach a high intensity in the target area. Absorption of the ultrasound energy creates an increase in temperature, which destroys tissue. A cooling balloon surrounding the probe protects the rectal mucosa from the high temperature. A urethral or suprapubic catheter is used after the procedure.\n\nTransurethral resection of the prostate may be carried out immediately before the HIFU treatment, to reduce the volume of the prostate and minimise the amount of necrotic debris left after the procedure. HIFU treatment can be repeated if necessary.\n\n# Efficacy\n\nThe evidence was based on case series and the main outcomes reported were negative biopsy rates and PSA nadir levels. Some studies reported disease-free survival rates but the criteria used to define disease varied. A systematic review, including eight case series, reported a negative biopsy rate of 60% (37/62) in one study with follow up not specified, and 80% (75/94) in a study with 3-year follow up. In three further studies in the review, the proportion of patients without clinical or biochemical evidence of disease ranged from 56% (28/50) at 24 months to 66% (67/102) at 19 months.\n\nThree additional case series reported negative biopsy rates between 87% (251/288) in a study with mean follow up of 13 months and 93% (128/137) in a study with mean follow up of 22.5 months. One of these studies, which included 146 patients, also reported disease-free survival rates of 54% or 71.5%, depending on the criteria used to define disease-free status. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered that long-term data are needed to establish whether the procedure reduces prostate-cancer-specific mortality.\n\n# Safety\n\nUrinary tract infections and stress incontinence were the most commonly reported complications, affecting between 4% (6/137) and 48% (46/96) and between 8% (9/111) and 23% (23/102) of patients in two case series. Recto-urethral fistula was reported in 0.7% (1/137) and 3% (3/111) of patients. Four studies reported rates of impotence after the procedure between 24% (75/315) and 100% (62/62) but the proportion of men who were potent before treatment was inadequately reported. Other complications included prolonged urinary retention, urge incontinence, urgency, bladder neck stenosis, urethral stenosis, urethritis, prostatic abscess, epididymitis, asymptomatic rectal burns and chronic pelvic pain. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors listed urinary incontinence, rectal fistula, bowel perforation and erectile dysfunction as potential adverse events but noted that HIFU appears to be safer than alternative radical treatments for prostate cancer. Two Specialist Advisors noted that there were concerns regarding control of local heating and limiting sound energy to the target area.\n\n# Other comments\n\nIn recommending that further research and audit should address long-term survival, it is noted that prostate cancer patients frequently die from unrelated causes.\n\nMost of the evidence related to localised prostate cancer.", 'Other NICE recommendations on high-intensity focused ultrasound for prostate cancer': "Further recommendations have been made as part of the clinical guideline on prostate cancer published in February 2008, as follows:\n\nHigh intensity focused ultrasound (HIFU) and cryotherapy are not recommended for men with localised prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions.\n\nClinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available in NICE's guideline on prostate cancer diagnosis and management. The IP guidance on high-intensity focused ultrasound for prostate cancer remains current, and should be read in conjunction with the clinical guideline.", 'Further information': "NICE has issued guidance on urological cancer services, which includes prostate cancer. NICE has also issued interventional procedures guidance on laparoscopic radical prostatectomy and salvage cryotherapy for recurrent prostate cancer.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind."}	https://www.nice.org.uk/guidance/ipg118
bb08dd365f6c0369f66be7b565c59bbb7f41da8f	nice	Artificial metacarpophalangeal and interphalangeal joint replacement for end-stage arthritis	Artificial metacarpophalangeal and interphalangeal joint replacement for end-stage arthritis # Guidance Current evidence on the safety and efficacy of artificial metacarpophalangeal (MCP) and interphalangeal (IP) joint replacement of the hand for end-stage arthritis appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Most of the evidence was based on a single type of joint prosthesis. The range of prostheses used is continually changing and clinicians are encouraged to submit their results to the appropriate joint-replacement registry for evaluation of long-term outcomes of different types of prosthesis.# The procedure # Indications Arthritis of the hand joints is a common condition that deteriorates over time, although the severity of symptoms, rate of deterioration and functional effects are variable. Artificial metacarpophalangeal (MCP) and interphalangeal (IP) joints are used primarily to treat the pain of severe end-stage arthritis. Conservative treatments for arthritis of the hand include anti-inflammatory and analgesic medication, and steroid injections. Other treatments include complete joint excision without replacement (also called excision arthroplasty), native graft arthroplasties (in which the patient's own tissue, typically tendon, is interposed in the space left after joint excision) and fusion of joints (arthrodesis). # Outline of the procedure A general anaesthetic is usually used and a tourniquet is applied to the affected arm to maintain a blood-free operation site. An incision is made over the diseased joint and the tendons are retracted. The joint is removed with an oscillating saw and a prosthetic joint (typically made of a silicone-based material) is inserted in its place. A splint is applied to the fingers. # Efficacy Four studies reported efficacy data on a total of 125 patients and 202 joints. Pain relief was the main outcome reported. In three studies, the proportion of joints with less pain after the procedure ranged from 97% (67/69) to 100% (31/31). Two studies, including 74 joints with osteoarthritis, reported that there was no significant improvement in the range of movement, but another study reported that 71% (22/31) of joints had improved power and 81% (25/31) had improved dexterity. Two studies reported that 95% (18/19) and 87% (27/31) of patients were satisfied with the result of the surgery, after mean follow-up of 3 years and 6 years, respectively. For more details, refer to the sources of evidence. The Specialist Advisors noted concerns regarding the long-term benefits compared with the use of arthrodesis. # Safety A systematic review, including 70 articles (15,556 MCP and IP joint replacements), reported on complications. The most common complication was change to surrounding bones, including bone cysts, osteolysis, resorption and heterotopic bone formation, in 4% (577/15,556) of implants. Other complications included implant fracture in 2% (352/15,556) of joints, implant loosening in less than 1% (114/15,556) and infection in less than 1% (86/15,556). Removal of the implant was necessary in 1% (143/15,556) of joints. The reasons for removal included implant fracture, infection, loosening, pain and synovitis. Two small case series reported that 7% (5/69) and 3% (1/31) of implants had fractured after mean follow-up periods of 3 years and 6 years, respectively. For more details, refer to the sources of evidence. The Specialist Advisors listed potential adverse effects including stiffness, loosening of the prosthesis, generation of wear debris, bone resorption, nerve injury, wound haematoma, silicone synovitis, infection and prosthesis fatigue. # Other comments This procedure is primarily used to treat pain in end-stage arthritis.# Further information NICE has issued guidance on artificial trapeziometacarpal joint replacement for end-stage osteoarthritis. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind. # Sources of evidence The evidence considered by the interventional procedures advisory committee is described in the overview to this guidance.	{'Guidance': 'Current evidence on the safety and efficacy of artificial metacarpophalangeal (MCP) and interphalangeal (IP) joint replacement of the hand for end-stage arthritis appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nMost of the evidence was based on a single type of joint prosthesis. The range of prostheses used is continually changing and clinicians are encouraged to submit their results to the appropriate joint-replacement registry for evaluation of long-term outcomes of different types of prosthesis.', 'The procedure': "# Indications\n\nArthritis of the hand joints is a common condition that deteriorates over time, although the severity of symptoms, rate of deterioration and functional effects are variable. Artificial metacarpophalangeal (MCP) and interphalangeal (IP) joints are used primarily to treat the pain of severe end-stage arthritis.\n\nConservative treatments for arthritis of the hand include anti-inflammatory and analgesic medication, and steroid injections. Other treatments include complete joint excision without replacement (also called excision arthroplasty), native graft arthroplasties (in which the patient's own tissue, typically tendon, is interposed in the space left after joint excision) and fusion of joints (arthrodesis).\n\n# Outline of the procedure\n\nA general anaesthetic is usually used and a tourniquet is applied to the affected arm to maintain a blood-free operation site. An incision is made over the diseased joint and the tendons are retracted. The joint is removed with an oscillating saw and a prosthetic joint (typically made of a silicone-based material) is inserted in its place. A splint is applied to the fingers.\n\n# Efficacy\n\nFour studies reported efficacy data on a total of 125 patients and 202 joints. Pain relief was the main outcome reported. In three studies, the proportion of joints with less pain after the procedure ranged from 97% (67/69) to 100% (31/31). Two studies, including 74 joints with osteoarthritis, reported that there was no significant improvement in the range of movement, but another study reported that 71% (22/31) of joints had improved power and 81% (25/31) had improved dexterity. Two studies reported that 95% (18/19) and 87% (27/31) of patients were satisfied with the result of the surgery, after mean follow-up of 3 years and 6 years, respectively. For more details, refer to the sources of evidence.\n\nThe Specialist Advisors noted concerns regarding the long-term benefits compared with the use of arthrodesis.\n\n# Safety\n\nA systematic review, including 70 articles (15,556 MCP and IP joint replacements), reported on complications. The most common complication was change to surrounding bones, including bone cysts, osteolysis, resorption and heterotopic bone formation, in 4% (577/15,556) of implants. Other complications included implant fracture in 2% (352/15,556) of joints, implant loosening in less than 1% (114/15,556) and infection in less than 1% (86/15,556). Removal of the implant was necessary in 1% (143/15,556) of joints. The reasons for removal included implant fracture, infection, loosening, pain and synovitis. Two small case series reported that 7% (5/69) and 3% (1/31) of implants had fractured after mean follow-up periods of 3 years and 6 years, respectively. For more details, refer to the sources of evidence.\n\nThe Specialist Advisors listed potential adverse effects including stiffness, loosening of the prosthesis, generation of wear debris, bone resorption, nerve injury, wound haematoma, silicone synovitis, infection and prosthesis fatigue.\n\n# Other comments\n\nThis procedure is primarily used to treat pain in end-stage arthritis.", 'Further information': 'NICE has issued guidance on artificial trapeziometacarpal joint replacement for end-stage osteoarthritis.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.\n\n# Sources of evidence\n\nThe evidence considered by the interventional procedures advisory committee is described in the overview to this guidance.'}	https://www.nice.org.uk/guidance/ipg110
2baeed9d3969b5a8e494c438d2d2914d4be3d15b	nice	Artificial trapeziometacarpal joint replacement for end-stage osteoarthritis	Artificial trapeziometacarpal joint replacement for end-stage osteoarthritis # Guidance Current evidence on the safety and efficacy of artificial trapeziometacarpal (TMC) joint replacement for end-stage osteoarthritis appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Most of the evidence was based on a single type of joint prosthesis. The range of prostheses used is continually changing and clinicians are encouraged to submit their results to the appropriate joint replacement registry for evaluation of long-term outcomes of different types of prosthesis.# The procedure # Indications Osteoarthritis of the hand joints is a common condition that deteriorates over time, although the severity of symptoms, rate of deterioration and functional effects are variable. Artificial trapeziometacarpal (TMC) joints are primarily used to treat the pain of severe end-stage osteoarthritis. Conservative treatments for osteoarthritis of the hand include anti-inflammatory and analgesic medication, and steroid injections. Other treatments include complete joint excision without replacement (also called excision arthroplasty), native graft arthroplasties (in which the patient's own tissue, typically tendon, is interposed in the space left after joint excision) and fusion of joints (arthrodesis). # Outline of the procedure A general anaesthetic is usually used and a tourniquet is applied to the affected arm to maintain a blood-free operation site. An incision is made over the diseased joint and the tendons are retracted. The joint is removed with an oscillating saw, and a prosthetic joint (typically made of a silicone-based material) is inserted in its place. A splint is applied to the fingers. # Efficacy The five studies reviewed described a total of 257 patients. In one small randomised controlled trial comparing silicone prosthesis arthroplasty with tendon arthroplasty, the proportion of satisfied patients was similar in the two groups (80% versus 85%; 12/15 and 11/13 patients, respectively). The mean pain reduction was also similar in both groups of patients. A non-randomised comparative study of 89 patients reported significantly less pain at 12 months in 50 joints treated with a silicone prosthesis arthroplasty, compared with 54 joints treated with sling excision arthroplasty (p < 0.01). Patients in the silicone prosthesis group reported better function for most tasks (statistically significant for being able to carry a milk bottle and taking off the handbrake of a car), but there was no statistically significant difference in patient satisfaction between the two groups. A case series of 58 patients with a mean follow-up of 16 years reported that maximal improvement was achieved at 5 years. A small case series reported that 88% (22/25) of patients had less pain than before the procedure after a mean follow-up of 6.5 years. For more details, refer to the sources of evidence section. The specialist advisors considered that the long-term benefits of this procedure need to be compared with the long-term benefits of established procedures such as excision arthroplasty and joint fusion. # Safety Four studies comprising a total of 242 patients reported on safety of the procedure. In 3 studies, between 6% (4/62) and 20% (6/30) of implants had to be removed. The reasons for removal were listed as subluxation, fracture, dislocation, infection, pain, stiffness, and silicone synovitis. One study of 90 patients reported that components loosened in 16% (13/79) of replacement joints after a mean follow-up period of 6 years. Two studies reported that a small number of patients had reflex sympathetic dystrophy after the procedure (3% and 4% of patients). For more details, refer to the sources of evidence section. The Specialist Advisors considered that the main potential adverse effects include infection, stiffness, nerve injury, silicone synovitis and failure of the joint replacement.# Further information The Institute has issued guidance on artificial metacarpophalangeal and interphalangeal joint replacement for end-stage arthritis. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': 'Current evidence on the safety and efficacy of artificial trapeziometacarpal (TMC) joint replacement for end-stage osteoarthritis appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nMost of the evidence was based on a single type of joint prosthesis. The range of prostheses used is continually changing and clinicians are encouraged to submit their results to the appropriate joint replacement registry for evaluation of long-term outcomes of different types of prosthesis.', 'The procedure': "# Indications\n\nOsteoarthritis of the hand joints is a common condition that deteriorates over time, although the severity of symptoms, rate of deterioration and functional effects are variable. Artificial trapeziometacarpal (TMC) joints are primarily used to treat the pain of severe end-stage osteoarthritis.\n\nConservative treatments for osteoarthritis of the hand include anti-inflammatory and analgesic medication, and steroid injections. Other treatments include complete joint excision without replacement (also called excision arthroplasty), native graft arthroplasties (in which the patient's own tissue, typically tendon, is interposed in the space left after joint excision) and fusion of joints (arthrodesis).\n\n# Outline of the procedure\n\nA general anaesthetic is usually used and a tourniquet is applied to the affected arm to maintain a blood-free operation site. An incision is made over the diseased joint and the tendons are retracted. The joint is removed with an oscillating saw, and a prosthetic joint (typically made of a silicone-based material) is inserted in its place. A splint is applied to the fingers.\n\n# Efficacy\n\nThe five studies reviewed described a total of 257 patients. In one small randomised controlled trial comparing silicone prosthesis arthroplasty with tendon arthroplasty, the proportion of satisfied patients was similar in the two groups (80% versus 85%; 12/15 and 11/13 patients, respectively). The mean pain reduction was also similar in both groups of patients. A non-randomised comparative study of 89 patients reported significantly less pain at 12 months in 50 joints treated with a silicone prosthesis arthroplasty, compared with 54 joints treated with sling excision arthroplasty (p < 0.01). Patients in the silicone prosthesis group reported better function for most tasks (statistically significant for being able to carry a milk bottle and taking off the handbrake of a car), but there was no statistically significant difference in patient satisfaction between the two groups. A case series of 58 patients with a mean follow-up of 16 years reported that maximal improvement was achieved at 5 years. A small case series reported that 88% (22/25) of patients had less pain than before the procedure after a mean follow-up of 6.5 years. For more details, refer to the sources of evidence section.\n\nThe specialist advisors considered that the long-term benefits of this procedure need to be compared with the long-term benefits of established procedures such as excision arthroplasty and joint fusion.\n\n# Safety\n\nFour studies comprising a total of 242 patients reported on safety of the procedure. In 3 studies, between 6% (4/62) and 20% (6/30) of implants had to be removed. The reasons for removal were listed as subluxation, fracture, dislocation, infection, pain, stiffness, and silicone synovitis. One study of 90 patients reported that components loosened in 16% (13/79) of replacement joints after a mean follow-up period of 6 years. Two studies reported that a small number of patients had reflex sympathetic dystrophy after the procedure (3% [2/58] and 4% [1/25] of patients). For more details, refer to the sources of evidence section.\n\nThe Specialist Advisors considered that the main potential adverse effects include infection, stiffness, nerve injury, silicone synovitis and failure of the joint replacement.", 'Further information': "The Institute has issued guidance on artificial metacarpophalangeal and interphalangeal joint replacement for end-stage arthritis.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind."}	https://www.nice.org.uk/guidance/ipg111
1a970f20ae3fe6d66484f388c0122da7c298dfa5	nice	Endoscopic dacryocystorhinostomy	Endoscopic dacryocystorhinostomy # Guidance Current evidence on the safety and efficacy of endoscopic dacryocystorhinostomy appears adequate to support use of the procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Specific training is particularly important and the Royal College of Ophthalmologists and the British Association of Otorhinolaryngologists – Head & Neck Surgeons have agreed to produce joint standards for training.# The procedure # Indications Endoscopic dacryocystorhinostomy (DCR) is indicated for patients with lacrimal sac obstruction or nasolacrimal duct obstruction (NLDO). NLDO is common, and presenting symptoms include watering of the eye and dacryocystitis (infection). Endoscopic DCR is usually considered for patients who have been refractory to conventional treatment such as warm compresses, massage and probing of the nasolacrimal duct. If NLDO is left untreated, the symptoms persist and may be distressing for the patient. Endoscopic DCR is one of several techniques used to unblock the nasolacrimal duct. The standard approach for DCR is open surgery. # Outline of the procedure Endoscopic DCR is a minimally invasive procedure used to bypass the nasolacrimal duct. Under local anaesthesia, an endoscope is inserted into the nose. Surgical instruments or a laser are used to create an opening between the nose and the lacrimal sac through the mucosa and intervening bone. Silicone tubes can be inserted with the aim of improving long-term patency. # Efficacy One randomised controlled trial reported success rates of 75% (24/32) for endoscopic DCR. After 12 months, 59% (19/32) of patients were asymptomatic. A large study that compared the use of lasers with electrocautery instruments for endoscopic DCR in 398 patients reported success rates of 92% (222/242) and 90% (28/31) using two different laser types, and 87% (39/45) for electrocautery instruments. At 1-year follow-up, 83% (65/78) of patients were symptom-free after a laser-assisted procedure in a case series of patients with dacryostenosis. For more details, refer to the Sources of evidence section. The Specialist Advisors stated that endoscopic DCR is now established practice, that failure rates are similar to conventional treatment, and that healing rates may be quicker. # Safety The rates of reported complications were low and they commonly included minor bleeding. Adverse events were found to occur at similar rates with or without the use of lasers. One study of 78 consecutive patients undergoing laser-assisted DCR observed no incidents of bleeding or infection. For more details, refer to the Sources of evidence section. The Specialist Advisors stated that infection was a potential adverse event, and that scar tissue formation at the site of the laser beam caused lower success rates. # Other comments It was noted that the impact of using a silicone tube to maintain patency was uncertain. The evidence on this procedure related to adults. The treatment of the watering eye in infants was not considered.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': 'Current evidence on the safety and efficacy of endoscopic dacryocystorhinostomy appears adequate to support use of the procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nSpecific training is particularly important and the Royal College of Ophthalmologists and the British Association of Otorhinolaryngologists – Head & Neck Surgeons have agreed to produce joint standards for training.', 'The procedure': '# Indications\n\nEndoscopic dacryocystorhinostomy (DCR) is indicated for patients with lacrimal sac obstruction or nasolacrimal duct obstruction (NLDO). NLDO is common, and presenting symptoms include watering of the eye and dacryocystitis (infection). Endoscopic DCR is usually considered for patients who have been refractory to conventional treatment such as warm compresses, massage and probing of the nasolacrimal duct. If NLDO is left untreated, the symptoms persist and may be distressing for the patient.\n\nEndoscopic DCR is one of several techniques used to unblock the nasolacrimal duct. The standard approach for DCR is open surgery.\n\n# Outline of the procedure\n\nEndoscopic DCR is a minimally invasive procedure used to bypass the nasolacrimal duct.\n\nUnder local anaesthesia, an endoscope is inserted into the nose. Surgical instruments or a laser are used to create an opening between the nose and the lacrimal sac through the mucosa and intervening bone. Silicone tubes can be inserted with the aim of improving long-term patency.\n\n# Efficacy\n\nOne randomised controlled trial reported success rates of 75% (24/32) for endoscopic DCR. After 12 months, 59% (19/32) of patients were asymptomatic. A large study that compared the use of lasers with electrocautery instruments for endoscopic DCR in 398 patients reported success rates of 92% (222/242) and 90% (28/31) using two different laser types, and 87% (39/45) for electrocautery instruments. At 1-year follow-up, 83% (65/78) of patients were symptom-free after a laser-assisted procedure in a case series of patients with dacryostenosis. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors stated that endoscopic DCR is now established practice, that failure rates are similar to conventional treatment, and that healing rates may be quicker.\n\n# Safety\n\nThe rates of reported complications were low and they commonly included minor bleeding. Adverse events were found to occur at similar rates with or without the use of lasers. One study of 78 consecutive patients undergoing laser-assisted DCR observed no incidents of bleeding or infection. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors stated that infection was a potential adverse event, and that scar tissue formation at the site of the laser beam caused lower success rates.\n\n# Other comments\n\nIt was noted that the impact of using a silicone tube to maintain patency was uncertain.\n\nThe evidence on this procedure related to adults. The treatment of the watering eye in infants was not considered.', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind."}	https://www.nice.org.uk/guidance/ipg113
f1d482b70351aa648ca546a744bccafc72544e0f	nice	Lung volume reduction surgery for advanced emphysema	Lung volume reduction surgery for advanced emphysema # Guidance Current evidence on the safety and efficacy of lung volume reduction surgery for advanced emphysema appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Clinicians wishing to use lung volume reduction surgery for advanced emphysema should ensure that patients are fully informed about the risks of the procedure and the likelihood of deterioration in the longer term. Use of NICE's information for the public is recommended. Patient selection is important because mortality is increased in patients with the most seriously compromised lung function. NICE has issued a clinical guideline on chronic obstructive pulmonary disease. The procedure should be undertaken by a multidisciplinary team that includes a respiratory physician, specialists in pulmonary rehabilitation and a thoracic surgeon.# The procedure # Indications Emphysema is a chronic lung disease. The walls of the air sacs (alveoli) in the lung weaken and disintegrate, leaving behind abnormally large air spaces that remain filled with air even when the patient breathes out. These air spaces may coalesce to form larger air-filled sacs called bullae. The surface area of the alveoli is decreased, so there is less space for the exchange of oxygen and carbon dioxide. This leads to reduced levels of oxygen in the blood. The most common symptoms of emphysema are shortness of breath (dyspnoea), coughing, fatigue and weight loss. Emphysema often co-exists with chronic bronchitis. Both of these conditions may be described by the more general term of chronic obstructive pulmonary disease (COPD). Treatment for COPD involves a multidisciplinary approach, which may include education, exercise, breathing retraining, smoking cessation, oral and inhaled medication, oxygen therapy, and lung transplantation. Lung volume reduction surgery may be an option for patients with severe symptoms for whom conservative treatments have proved inadequate. # Outline of the procedure Lung volume reduction surgery is a palliative treatment that aims to remove the least functional part of the lungs. Computed tomography (CT) and perfusion scanning are used to identify the diseased lung tissue. The diseased part of the lung can be accessed by various techniques including median sternotomy, video-assisted thoracoscopy and thoracotomy. The first two are the most common techniques. Median sternotomy involves cutting through the sternum to open the chest. The video-assisted procedure involves making a number of small incisions in both sides of the chest to allow the insertion of instruments into the chest between the ribs. A thoracotomy involves making an incision between the ribs on one side of the chest and separating the ribs to access the lung. The aim of the surgery is to reduce the volume of the lung. This is done by using a surgical stapling device to cut and seal the tissue, laser ablation to shrink lung volume, or a combination of both. Once the tissue has been removed, the lung is re-inflated and the chest closed. # Efficacy Evidence on efficacy indicates that in certain patients lung function, exercise performance and quality of life are improved in the short term after lung volume reduction surgery. These results have been relatively consistent across study designs and were confirmed in the National Emphysema Treatment Trial, a recent large-scale randomised controlled trial comparing surgery with medical therapy. The National Emphysema Treatment Trial randomised 1218 patients, of whom 580 underwent surgery. At 24 months, exercise capacity had improved in 15% (54/371) of patients in the surgery group compared with 3% (10/378) of patients in the medical group (p < 0.001). Quality of life had also improved in the surgical group (121/371) as compared with the medical group (34/378) at 24 months (33% versus 9%, p < 0.001). However, the trial found no difference in overall mortality between the two groups (0.11 deaths per person-year, risk ratio 1.01, p = 0.90). For more details, refer to the Sources of evidence section. The Specialist Advisors considered that the procedure is beneficial for a select proportion of patients, but the benefit tends to decline with time. # Safety The most common complication was persistent air leak from the lung. In one study of 250 patients, 45% (113/250) of patients experienced prolonged air leaks lasting more than 7 days, with 8 of these patients (3%) requiring a subsequent operation. Other complications in this series included pneumonia 10% (24/250), in-hospital mortality 5% (12/250), myocardial infarction 2% (5/250), deep vein thrombosis 2% (4/250), small bowel obstruction 2% (6/250) and phrenic nerve injury < 1% (2/250). For more details, refer to the Sources of evidence section. Complications include those that may arise from pre-existing co-morbidities as well as those that are directly due to the surgery. The Specialist Advisors considered that the risks of surgery were well known. They listed the main complications as being air leaks, chest infections and respiratory failure. # Other comments It was noted that endobronchial techniques are being used increasingly as an alternative to this procedure.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and efficacy of lung volume reduction surgery for advanced emphysema appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians wishing to use lung volume reduction surgery for advanced emphysema should ensure that patients are fully informed about the risks of the procedure and the likelihood of deterioration in the longer term. Use of NICE's information for the public is recommended.\n\nPatient selection is important because mortality is increased in patients with the most seriously compromised lung function. NICE has issued a clinical guideline on chronic obstructive pulmonary disease.\n\nThe procedure should be undertaken by a multidisciplinary team that includes a respiratory physician, specialists in pulmonary rehabilitation and a thoracic surgeon.", 'The procedure': '# Indications\n\nEmphysema is a chronic lung disease. The walls of the air sacs (alveoli) in the lung weaken and disintegrate, leaving behind abnormally large air spaces that remain filled with air even when the patient breathes out. These air spaces may coalesce to form larger air-filled sacs called bullae. The surface area of the alveoli is decreased, so there is less space for the exchange of oxygen and carbon dioxide. This leads to reduced levels of oxygen in the blood. The most common symptoms of emphysema are shortness of breath (dyspnoea), coughing, fatigue and weight loss.\n\nEmphysema often co-exists with chronic bronchitis. Both of these conditions may be described by the more general term of chronic obstructive pulmonary disease (COPD).\n\nTreatment for COPD involves a multidisciplinary approach, which may include education, exercise, breathing retraining, smoking cessation, oral and inhaled medication, oxygen therapy, and lung transplantation. Lung volume reduction surgery may be an option for patients with severe symptoms for whom conservative treatments have proved inadequate.\n\n# Outline of the procedure\n\nLung volume reduction surgery is a palliative treatment that aims to remove the least functional part of the lungs. Computed tomography (CT) and perfusion scanning are used to identify the diseased lung tissue. The diseased part of the lung can be accessed by various techniques including median sternotomy, video-assisted thoracoscopy and thoracotomy. The first two are the most common techniques. Median sternotomy involves cutting through the sternum to open the chest. The video-assisted procedure involves making a number of small incisions in both sides of the chest to allow the insertion of instruments into the chest between the ribs. A thoracotomy involves making an incision between the ribs on one side of the chest and separating the ribs to access the lung.\n\nThe aim of the surgery is to reduce the volume of the lung. This is done by using a surgical stapling device to cut and seal the tissue, laser ablation to shrink lung volume, or a combination of both. Once the tissue has been removed, the lung is re-inflated and the chest closed.\n\n# Efficacy\n\nEvidence on efficacy indicates that in certain patients lung function, exercise performance and quality of life are improved in the short term after lung volume reduction surgery. These results have been relatively consistent across study designs and were confirmed in the National Emphysema Treatment Trial, a recent large-scale randomised controlled trial comparing surgery with medical therapy.\n\nThe National Emphysema Treatment Trial randomised 1218 patients, of whom 580 underwent surgery. At 24 months, exercise capacity had improved in 15% (54/371) of patients in the surgery group compared with 3% (10/378) of patients in the medical group (p < 0.001). Quality of life had also improved in the surgical group (121/371) as compared with the medical group (34/378) at 24 months (33% versus 9%, p < 0.001). However, the trial found no difference in overall mortality between the two groups (0.11 deaths per person-year, risk ratio 1.01, p = 0.90). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered that the procedure is beneficial for a select proportion of patients, but the benefit tends to decline with time.\n\n# Safety\n\nThe most common complication was persistent air leak from the lung. In one study of 250 patients, 45% (113/250) of patients experienced prolonged air leaks lasting more than 7 days, with 8 of these patients (3%) requiring a subsequent operation. Other complications in this series included pneumonia 10% (24/250), in-hospital mortality 5% (12/250), myocardial infarction 2% (5/250), deep vein thrombosis 2% (4/250), small bowel obstruction 2% (6/250) and phrenic nerve injury < 1% (2/250). For more details, refer to the Sources of evidence section.\n\nComplications include those that may arise from pre-existing co-morbidities as well as those that are directly due to the surgery.\n\nThe Specialist Advisors considered that the risks of surgery were well known. They listed the main complications as being air leaks, chest infections and respiratory failure.\n\n# Other comments\n\nIt was noted that endobronchial techniques are being used increasingly as an alternative to this procedure.', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind."}	https://www.nice.org.uk/guidance/ipg114
5a88663772a2d6c276ee05e44bc0dbe84ab013dc	nice	Coil embolisation of unruptured intracranial aneurysms	Coil embolisation of unruptured intracranial aneurysms The Interventional Procedures Advisory Committee (IPAC) originally considered this procedure as part of coil embolisation for intracranial aneurysms. However, as a result of comments received during the initial consultation in June 2003, IPAC decided to consider the procedure separately for ruptured intracranial aneurysms and for unruptured intracranial aneurysms. # Guidance Current evidence suggests that coil embolisation is efficacious in obliterating unruptured intracranial aneurysms and that its safety is similar to that of surgical treatment. The annual risk of haemorrhage from unruptured intracranial aneurysms varies widely, depending on their site and size; and the lifetime risk depends on life expectancy and other factors. The decision to treat unruptured intracranial aneurysms by coil embolisation therefore requires judgement of the risks for each patient, and recognition of the importance of patient choice. Clinicians wishing to undertake this procedure should ensure that: normal arrangements are in place for audit and clinical governance patients understand the relative risks of coil embolisation and surgery compared to the risk of having no treatment when giving their consent for this treatment. Use of NICE's information for the public on coil embolisation of unruptured cranial aneurysms is recommended. The procedure should only be performed in specialist units with expertise in the endovascular treatment of intracranial aneurysms.# The procedure # Indications Intracranial aneurysms are small balloon-like dilated portions of blood vessels that may occasionally rupture, causing haemorrhage, stroke or death. Usually, the cause is unknown, but people with genetic causes of weak blood vessels are more likely to develop aneurysms. The traditional treatment for ruptured or unruptured aneurysms involves open surgery to clip the abnormal blood vessels inside the skull. # Outline of the procedure The coil technique involves approaching the aneurysm from inside the diseased blood vessel, thereby avoiding the need to open the skull. A thin tube containing the coil on a guidewire is inserted into a large artery, usually in the groin, and passed up into the skull under radiological guidance. The coil is placed inside the aneurysm and detached from the guidewire. Once in position, it causes clotting and stops blood from entering the aneurysm. Multiple coils may be inserted into the aneurysm through the same tube until the aneurysm is filled with coils. The coil technique is mainly carried out on ruptured aneurysms but may also be used to treat unruptured aneurysms. # Efficacy In a large observational study, it was reported that overall morbidity and mortality associated with endovascular repair was 9% (41/451) at 1 year after having the procedure, compared with 12% (233/1917) for surgery. Similar results were reported in smaller studies comparing the two techniques. However, these comparisons are difficult because patient characteristics differed between the two groups; for example, those who underwent endovascular repair were often older than those who had surgery. For the patients undergoing endovascular repair by coil embolisation in the International Study of Unruptured Intracranial Aneurysms, obliteration was complete in 55% (207/379) of patients, incomplete in 24% (91/379), unsuccessful in 18% (67/379), and unknown in 3% (12/379) of patients. At 1 year after the procedure, less than 1% of patients (4/451) had a moderate or severe disability, as measured by the Rankin score. In other studies on this procedure, the rate of permanent complications ranged from 5% (6/116) to 8% (3/38). For more details, refer to the Sources of evidence section. The Specialist Advisors considered that the main uncertainty related to the long-term durability of the procedure. # Safety In a retrospective study of 62 patients, the procedure-related complication rate was 23% (14/62) after coil embolisation. Major complications resulting in reduced functional status were reported in five patients (8%) and minor complications causing prolonged hospitalisation were reported in nine patients (15%). Adverse events during initial and follow-up hospitalisation included intra- or postoperative rupture (6%, 4/62 patients) and cranial neuropathy (11%, 7/62 patients). For more details, refer to the Sources of evidence section. In the large observational study, perioperative haemorrhage was noted in 2% (10/451) and cerebral infarction in 6% (26/451) of patients who underwent endovascular repair. The Specialist Advisors considered that this was a safe procedure. One Advisor noted that complications during the procedure include rupture of the aneurysm or thrombo-embolic occlusion of intracranial vessels, but these complications are uncommon. There is also a small risk of delayed haemorrhage from the aneurysm.# Further information This guidance relates to unruptured aneurysms. See also published separate NICE guidance on the use of coil embolisation for ruptured intracranial aneurysms. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind. ISBN: 978-1-4731-3985-5	{'Guidance': "Current evidence suggests that coil embolisation is efficacious in obliterating unruptured intracranial aneurysms and that its safety is similar to that of surgical treatment.\n\nThe annual risk of haemorrhage from unruptured intracranial aneurysms varies widely, depending on their site and size; and the lifetime risk depends on life expectancy and other factors. The decision to treat unruptured intracranial aneurysms by coil embolisation therefore requires judgement of the risks for each patient, and recognition of the importance of patient choice. Clinicians wishing to undertake this procedure should ensure that:\n\nnormal arrangements are in place for audit and clinical governance\n\npatients understand the relative risks of coil embolisation and surgery compared to the risk of having no treatment when giving their consent for this treatment. Use of NICE's information for the public on coil embolisation of unruptured cranial aneurysms is recommended.\n\nThe procedure should only be performed in specialist units with expertise in the endovascular treatment of intracranial aneurysms.", 'The procedure': '# Indications\n\nIntracranial aneurysms are small balloon-like dilated portions of blood vessels that may occasionally rupture, causing haemorrhage, stroke or death. Usually, the cause is unknown, but people with genetic causes of weak blood vessels are more likely to develop aneurysms.\n\nThe traditional treatment for ruptured or unruptured aneurysms involves open surgery to clip the abnormal blood vessels inside the skull.\n\n# Outline of the procedure\n\nThe coil technique involves approaching the aneurysm from inside the diseased blood vessel, thereby avoiding the need to open the skull. A thin tube containing the coil on a guidewire is inserted into a large artery, usually in the groin, and passed up into the skull under radiological guidance. The coil is placed inside the aneurysm and detached from the guidewire. Once in position, it causes clotting and stops blood from entering the aneurysm. Multiple coils may be inserted into the aneurysm through the same tube until the aneurysm is filled with coils.\n\nThe coil technique is mainly carried out on ruptured aneurysms but may also be used to treat unruptured aneurysms.\n\n# Efficacy\n\nIn a large observational study, it was reported that overall morbidity and mortality associated with endovascular repair was 9% (41/451) at 1 year after having the procedure, compared with 12% (233/1917) for surgery. Similar results were reported in smaller studies comparing the two techniques. However, these comparisons are difficult because patient characteristics differed between the two groups; for example, those who underwent endovascular repair were often older than those who had surgery.\n\nFor the patients undergoing endovascular repair by coil embolisation in the International Study of Unruptured Intracranial Aneurysms, obliteration was complete in 55% (207/379) of patients, incomplete in 24% (91/379), unsuccessful in 18% (67/379), and unknown in 3% (12/379) of patients. At 1 year after the procedure, less than 1% of patients (4/451) had a moderate or severe disability, as measured by the Rankin score. In other studies on this procedure, the rate of permanent complications ranged from 5% (6/116) to 8% (3/38). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered that the main uncertainty related to the long-term durability of the procedure.\n\n# Safety\n\nIn a retrospective study of 62 patients, the procedure-related complication rate was 23% (14/62) after coil embolisation. Major complications resulting in reduced functional status were reported in five patients (8%) and minor complications causing prolonged hospitalisation were reported in nine patients (15%). Adverse events during initial and follow-up hospitalisation included intra- or postoperative rupture (6%, 4/62 patients) and cranial neuropathy (11%, 7/62 patients). For more details, refer to the Sources of evidence section.\n\nIn the large observational study, perioperative haemorrhage was noted in 2% (10/451) and cerebral infarction in 6% (26/451) of patients who underwent endovascular repair.\n\nThe Specialist Advisors considered that this was a safe procedure. One Advisor noted that complications during the procedure include rupture of the aneurysm or thrombo-embolic occlusion of intracranial vessels, but these complications are uncommon. There is also a small risk of delayed haemorrhage from the aneurysm.', 'Further information': "This guidance relates to unruptured aneurysms. See also published separate NICE guidance on the use of coil embolisation for ruptured intracranial aneurysms.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.\n\nISBN: 978-1-4731-3985-5"}	https://www.nice.org.uk/guidance/ipg105	The Interventional Procedures Advisory Committee (IPAC) originally considered this procedure as part of coil embolisation for intracranial aneurysms. However, as a result of comments received during the initial consultation in June 2003, IPAC decided to consider the procedure separately for ruptured intracranial aneurysms and for unruptured intracranial aneurysms.
1a1da17c84c532c97c0fbda96ab5e9603759d55a	nice	Coil embolisation of ruptured intracranial aneurysms	Coil embolisation of ruptured intracranial aneurysms # Guidance Current evidence on the safety and efficacy of coil embolisation of ruptured intracranial aneurysms appears adequate to support use of the procedure, provided that normal arrangements are in place for consent, audit and clinical governance. The procedure should only be performed in specialist units with expertise in the endovascular treatment of intracranial aneurysms. Clear arrangements should be in place for the involvement of different clinical disciplines in treatment and follow-up. Patients with subarachnoid haemorrhage should have rapid access to appropriate specialist care.# The procedure # Indications Intracranial aneurysms are small balloon-like dilated portions of blood vessels that may occasionally rupture, causing haemorrhage, stroke or death. Usually the cause is unknown but people with genetic causes of weak blood vessels are more likely to develop aneurysms. Rupture of intracranial aneurysms causes subarachnoid haemorrhage and has a poor prognosis. About 30% of people die within 24 hours and a further 25–30% die within 4 weeks. The alternative treatment for ruptured intracranial aneurysm involves open surgery to clip the aneurysm inside the skull. # Outline of the procedure The coil technique involves approaching the aneurysm from inside the diseased blood vessel, thereby avoiding the need to open the skull. A thin tube containing the coil on a guidewire is inserted into a large artery, usually in the groin, and passed up into the skull under radiological guidance. The coil is placed inside the aneurysm and detached from the guidewire. Once in position, it causes clotting and stops blood from entering the aneurysm. Multiple coils may be inserted into the aneurysm through the same tube until the aneurysm is filled with coils. # Efficacy Use of the procedure was supported by a high-quality randomised controlled trial. In the trial, 'dependency' reflected a moderate to severe disability as defined by the modified Rankin score. The trial showed a 7% absolute risk reduction in dependency or death for patients treated with coils compared with patients treated by surgical clipping. For more details, refer to the Sources of evidence section. The Specialist Advisors stated that, in the short term, the procedure is more effective clinically than surgical clipping. However, the long-term durability of coil embolisation has not been established. # Safety Complications associated with the procedure included perforation of the aneurysm, intracranial haematoma and re-bleeding. In a case series of 403 patients, aneurysm perforation was observed in 11 patients (3%) and cerebral clot embolisation in 10 patients (2%). Coil migration occurred in two patients (0.5%). For more details, refer to the Sources of evidence section. The Specialist Advisors considered this procedure to be safer than surgical clipping. They stated that procedural mortality and stroke were the main adverse events. They also stated that there is a small risk of re-bleeding, and that this should be monitored over the long term. # Other comments Currently, evidence on the procedure's long-term results is limited to a mean follow-up of 3.7 years.# Further information This guidance relates to ruptured intracranial aneurysms. See also published separate NICE guidance on the use of coil embolisation for unruptured intracranial aneurysms. In 2002, the Royal College of Physicians published guidelines on the management of stroke, including subarachnoid haemorrhage. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind. ISBN: 978-1-4731-3986-2	{'Guidance': 'Current evidence on the safety and efficacy of coil embolisation of ruptured intracranial aneurysms appears adequate to support use of the procedure, provided that normal arrangements are in place for consent, audit and clinical governance.\n\nThe procedure should only be performed in specialist units with expertise in the endovascular treatment of intracranial aneurysms. Clear arrangements should be in place for the involvement of different clinical disciplines in treatment and follow-up.\n\nPatients with subarachnoid haemorrhage should have rapid access to appropriate specialist care.', 'The procedure': "# Indications\n\nIntracranial aneurysms are small balloon-like dilated portions of blood vessels that may occasionally rupture, causing haemorrhage, stroke or death. Usually the cause is unknown but people with genetic causes of weak blood vessels are more likely to develop aneurysms. Rupture of intracranial aneurysms causes subarachnoid haemorrhage and has a poor prognosis. About 30% of people die within 24 hours and a further 25–30% die within 4 weeks.\n\nThe alternative treatment for ruptured intracranial aneurysm involves open surgery to clip the aneurysm inside the skull.\n\n# Outline of the procedure\n\nThe coil technique involves approaching the aneurysm from inside the diseased blood vessel, thereby avoiding the need to open the skull. A thin tube containing the coil on a guidewire is inserted into a large artery, usually in the groin, and passed up into the skull under radiological guidance. The coil is placed inside the aneurysm and detached from the guidewire. Once in position, it causes clotting and stops blood from entering the aneurysm. Multiple coils may be inserted into the aneurysm through the same tube until the aneurysm is filled with coils.\n\n# Efficacy\n\nUse of the procedure was supported by a high-quality randomised controlled trial. In the trial, 'dependency' reflected a moderate to severe disability as defined by the modified Rankin score. The trial showed a 7% absolute risk reduction in dependency or death for patients treated with coils compared with patients treated by surgical clipping. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors stated that, in the short term, the procedure is more effective clinically than surgical clipping. However, the long-term durability of coil embolisation has not been established.\n\n# Safety\n\nComplications associated with the procedure included perforation of the aneurysm, intracranial haematoma and re-bleeding. In a case series of 403 patients, aneurysm perforation was observed in 11 patients (3%) and cerebral clot embolisation in 10 patients (2%). Coil migration occurred in two patients (0.5%). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered this procedure to be safer than surgical clipping. They stated that procedural mortality and stroke were the main adverse events. They also stated that there is a small risk of re-bleeding, and that this should be monitored over the long term.\n\n# Other comments\n\nCurrently, evidence on the procedure's long-term results is limited to a mean follow-up of 3.7 years.", 'Further information': "This guidance relates to ruptured intracranial aneurysms. See also published separate NICE guidance on the use of coil embolisation for unruptured intracranial aneurysms.\n\nIn 2002, the Royal College of Physicians published guidelines on the management of stroke, including subarachnoid haemorrhage.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.\n\nISBN: 978-1-4731-3986-2"}	https://www.nice.org.uk/guidance/ipg106
1e63f1630c262f90028a6db96ba14b66ebeed3b5	nice	Auditory brain stem implants	Auditory brain stem implants # Guidance Current evidence on the safety and efficacy of auditory brain stem implants appears adequate to support the use of this procedure by surgical teams experienced in this technique, provided that normal arrangements are in place for consent, audit and clinical governance.# The procedure # Indications This procedure is used to treat total deafness in both ears caused by damage to the vestibulocochlear nerve as a result of tumours or surgery. In people with vestibulocochlear nerve damage, hearing is not improved by hearing aids or cochlear implants. # Outline of the procedure The cochlear nucleus lies in the brain stem and is responsible for processing sound signals carried from the ear through the vestibulocochlear nerve. Auditory brain stem implants are electrodes placed in the cochlear nucleus. Removal of vestibulocochlear nerve tumours and placement of auditory brain stem implants are often done at the same time. An incision is made in the skin on the side of the head and some of the bone behind the ear is removed. This exposes the tumour so that it can be removed and also allows access to the brain stem beneath it. The electrodes can then be implanted into the cochlear nucleus. The brain stem may sometimes be approached through the back of the head. People with auditory brain stem implants wear an external receiver and speech processor. This device converts sounds into electrical signals, which are then sent to the implant. # Efficacy The evidence was limited to case series data. One study reported that 85% (75/88) of patients received auditory sensations when their implants were activated. In another study, some hearing was reported in 94% (51/54) of patients. For more details, refer to the Sources of evidence section. One Specialist Advisor commented that results were unpredictable. # Safety The main complications reported in the identified studies were: cerebrospinal fluid leak 3% (2/61); meningitis 2% (1/61); and pulmonary embolism 2% (1/54). A study of 61 patients reported no severe or serious non-auditory sensations. Tingling in various parts of the body was reported to be 'not uncommon' in a study of 88 patients. For more details, refer to the Sources of evidence section. The Specialist Advisors listed the potential adverse effects of the procedure as death, damage to lower cranial nerves, intracranial haematoma/brainstem stroke, meningitis, and implant-related infection. # Other comments This procedure is suitable for a small proportion of patients who have complete hearing loss for whom no alternative treatment would restore hearing. In the UK, this procedure has been performed on only a small number of patients in a limited number of hospitals. Long-term data are needed for this procedure.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': 'Current evidence on the safety and efficacy of auditory brain stem implants appears adequate to support the use of this procedure by surgical teams experienced in this technique, provided that normal arrangements are in place for consent, audit and clinical governance.', 'The procedure': "# Indications\n\nThis procedure is used to treat total deafness in both ears caused by damage to the vestibulocochlear nerve as a result of tumours or surgery.\n\nIn people with vestibulocochlear nerve damage, hearing is not improved by hearing aids or cochlear implants.\n\n# Outline of the procedure\n\nThe cochlear nucleus lies in the brain stem and is responsible for processing sound signals carried from the ear through the vestibulocochlear nerve. Auditory brain stem implants are electrodes placed in the cochlear nucleus.\n\nRemoval of vestibulocochlear nerve tumours and placement of auditory brain stem implants are often done at the same time. An incision is made in the skin on the side of the head and some of the bone behind the ear is removed. This exposes the tumour so that it can be removed and also allows access to the brain stem beneath it. The electrodes can then be implanted into the cochlear nucleus. The brain stem may sometimes be approached through the back of the head. People with auditory brain stem implants wear an external receiver and speech processor. This device converts sounds into electrical signals, which are then sent to the implant.\n\n# Efficacy\n\nThe evidence was limited to case series data. One study reported that 85% (75/88) of patients received auditory sensations when their implants were activated. In another study, some hearing was reported in 94% (51/54) of patients. For more details, refer to the Sources of evidence section.\n\nOne Specialist Advisor commented that results were unpredictable.\n\n# Safety\n\nThe main complications reported in the identified studies were: cerebrospinal fluid leak 3% (2/61); meningitis 2% (1/61); and pulmonary embolism 2% (1/54). A study of 61 patients reported no severe or serious non-auditory sensations. Tingling in various parts of the body was reported to be 'not uncommon' in a study of 88 patients. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors listed the potential adverse effects of the procedure as death, damage to lower cranial nerves, intracranial haematoma/brainstem stroke, meningitis, and implant-related infection.\n\n# Other comments\n\nThis procedure is suitable for a small proportion of patients who have complete hearing loss for whom no alternative treatment would restore hearing. In the UK, this procedure has been performed on only a small number of patients in a limited number of hospitals.\n\nLong-term data are needed for this procedure.", 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg108
cf1e73fd20469d78bea496ef90db7f6919fc8173	nice	Wireless capsule endoscopy for investigation of the small bowel	Wireless capsule endoscopy for investigation of the small bowel The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on wireless capsule endoscopy for investigation of the small bowel. # Guidance Current evidence on the safety and diagnostic yield of wireless capsule endoscopy appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. Clinicians should consider the use of other investigations prior to wireless capsule endoscopy, particularly in patients with Crohn's disease in whom strictures are suspected.# The procedure # Indications The main indication for this procedure is obscure gastrointestinal bleeding, which is defined as bleeding of unknown origin that persists or recurs after a negative initial endoscopy (colonoscopy and/or upper gastrointestinal endoscopy). Diagnosis may be difficult because bleeding can often be slow and/or intermittent. Patients may experience prolonged blood loss, leading to iron deficiency (anaemia) and a feeling of tiredness. Another important indication is the diagnosis and investigation of Crohn's disease. Bleeding from the small intestine can result from a number of conditions, including vascular lesions (angiodysplasia), small bowel tumours, and Crohn's disease (which may be suspected because of other symptoms). There are several methods for evaluation of the small bowel, including push enteroscopy (using a flexible endoscope through which images of the bowel's lining can be seen), intraoperative endoscopy and radiological small-bowel follow-through studies (in which the patient is required to drink barium and then have X-ray pictures taken of their abdomen at timed intervals). For most of these methods, the diagnostic accuracy (the ability to diagnose and exclude disease correctly) is poor. # Outline of the procedure The patient swallows a small capsule, usually after an overnight fast. This capsule consists of a camera, a light source and a wireless circuit for the acquisition and transmission of signals. As the capsule moves through the gastrointestinal tract, images are transmitted to a data recorder worn on a belt outside the body. These data are transferred to a computer for interpretation. The capsule is then passed in the patient's stool and is not used again. This procedure allows for the end-to-end visualisation of the small bowel. However, the presence of a motility disorder or stricture may preclude successful investigation. # Efficacy The published evidence suggests that wireless capsule endoscopy can detect a bleeding source in 31–76% (4/13–25/33) of patients with obscure gastrointestinal bleeding. In all studies, wireless capsule endoscopy had a higher diagnostic yield (proportion of patients identified with an apparent abnormality) than the comparator test. However, in most cases, patients had undergone extensive prior investigations, which would be likely to decrease the apparent diagnostic yield for the comparator procedures. It was not possible to determine the relative diagnostic performance (ability to detect correctly both the presence and absence of disease) of wireless capsule endoscopy compared with alternative conventional diagnostic tests. Several studies reported that wireless capsule endoscopy findings had changed patient management, but limited details were given as to whether change in management improved health outcomes. For more details, refer to the Sources of evidence section. For suspected Crohn's disease, the evidence suggests that wireless capsule endoscopy identifies small bowel lesions suggestive of this diagnosis in 43–71% (9/21–12/17) of patients with normal findings on conventional tests. Three studies reported that wireless capsule endoscopy findings had changed patient management, with two studies reporting clinical improvement in 83–100% (10/12–9/9) of patients. The available evidence, however, is not of sufficient quantity and quality to determine the relative diagnostic performance of wireless capsule endoscopy compared with alternative conventional diagnostic tests in diagnosing unselected patients with suspected Crohn's disease. For more details, refer to the Sources of evidence section. # Safety No significant complications were reported in the studies. The most commonly reported adverse events associated with the procedure were abdominal pain, nausea and vomiting. Delayed passage of the capsule was also reported in a number of studies but, in the majority of cases, this resolved without specific treatment. In a study of 200 patients performed to assess the complications associated with the use of wireless capsule endoscopy, six (3%) patients had complications associated with the procedure. These included two patients who experienced delayed passage and had to have surgery to remove the capsule, one patient who was unable to swallow the capsule and one patient who inadvertently aspirated the capsule. For more details, refer to the Sources of evidence section. The Specialist Advisors considered this to be a safe procedure. They noted that the most likely adverse event was lodgement of the capsule in narrowed areas of the small bowel, causing bowel obstruction. One Advisor commented that this complication was more likely in patients with suspected Crohn's disease than in patients with obscure gastrointestinal bleeding. # Other comments It was noted that there are other indications.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.	{'Guidance': "Current evidence on the safety and diagnostic yield of wireless capsule endoscopy appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nClinicians should consider the use of other investigations prior to wireless capsule endoscopy, particularly in patients with Crohn's disease in whom strictures are suspected.", 'The procedure': "# Indications\n\nThe main indication for this procedure is obscure gastrointestinal bleeding, which is defined as bleeding of unknown origin that persists or recurs after a negative initial endoscopy (colonoscopy and/or upper gastrointestinal endoscopy). Diagnosis may be difficult because bleeding can often be slow and/or intermittent. Patients may experience prolonged blood loss, leading to iron deficiency (anaemia) and a feeling of tiredness. Another important indication is the diagnosis and investigation of Crohn's disease.\n\nBleeding from the small intestine can result from a number of conditions, including vascular lesions (angiodysplasia), small bowel tumours, and Crohn's disease (which may be suspected because of other symptoms).\n\nThere are several methods for evaluation of the small bowel, including push enteroscopy (using a flexible endoscope through which images of the bowel's lining can be seen), intraoperative endoscopy and radiological small-bowel follow-through studies (in which the patient is required to drink barium and then have X-ray pictures taken of their abdomen at timed intervals). For most of these methods, the diagnostic accuracy (the ability to diagnose and exclude disease correctly) is poor.\n\n# Outline of the procedure\n\nThe patient swallows a small capsule, usually after an overnight fast. This capsule consists of a camera, a light source and a wireless circuit for the acquisition and transmission of signals. As the capsule moves through the gastrointestinal tract, images are transmitted to a data recorder worn on a belt outside the body. These data are transferred to a computer for interpretation. The capsule is then passed in the patient's stool and is not used again.\n\nThis procedure allows for the end-to-end visualisation of the small bowel. However, the presence of a motility disorder or stricture may preclude successful investigation.\n\n# Efficacy\n\nThe published evidence suggests that wireless capsule endoscopy can detect a bleeding source in 31–76% (4/13–25/33) of patients with obscure gastrointestinal bleeding. In all studies, wireless capsule endoscopy had a higher diagnostic yield (proportion of patients identified with an apparent abnormality) than the comparator test. However, in most cases, patients had undergone extensive prior investigations, which would be likely to decrease the apparent diagnostic yield for the comparator procedures. It was not possible to determine the relative diagnostic performance (ability to detect correctly both the presence and absence of disease) of wireless capsule endoscopy compared with alternative conventional diagnostic tests. Several studies reported that wireless capsule endoscopy findings had changed patient management, but limited details were given as to whether change in management improved health outcomes. For more details, refer to the Sources of evidence section.\n\nFor suspected Crohn's disease, the evidence suggests that wireless capsule endoscopy identifies small bowel lesions suggestive of this diagnosis in 43–71% (9/21–12/17) of patients with normal findings on conventional tests. Three studies reported that wireless capsule endoscopy findings had changed patient management, with two studies reporting clinical improvement in 83–100% (10/12–9/9) of patients. The available evidence, however, is not of sufficient quantity and quality to determine the relative diagnostic performance of wireless capsule endoscopy compared with alternative conventional diagnostic tests in diagnosing unselected patients with suspected Crohn's disease. For more details, refer to the Sources of evidence section.\n\n# Safety\n\nNo significant complications were reported in the studies. The most commonly reported adverse events associated with the procedure were abdominal pain, nausea and vomiting. Delayed passage of the capsule was also reported in a number of studies but, in the majority of cases, this resolved without specific treatment. In a study of 200 patients performed to assess the complications associated with the use of wireless capsule endoscopy, six (3%) patients had complications associated with the procedure. These included two patients who experienced delayed passage and had to have surgery to remove the capsule, one patient who was unable to swallow the capsule and one patient who inadvertently aspirated the capsule. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered this to be a safe procedure. They noted that the most likely adverse event was lodgement of the capsule in narrowed areas of the small bowel, causing bowel obstruction. One Advisor commented that this complication was more likely in patients with suspected Crohn's disease than in patients with obscure gastrointestinal bleeding.\n\n# Other comments\n\nIt was noted that there are other indications.", 'Further information': '# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the overview to this guidance.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.'}	https://www.nice.org.uk/guidance/ipg101	The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on wireless capsule endoscopy for investigation of the small bowel.
8a18d60a6cc8b4173e46c4deb15e7876c7b09254	nice	Sacral nerve stimulation for faecal incontinence	Sacral nerve stimulation for faecal incontinence # Guidance This document replaces previous guidance on sacral nerve stimulation for faecal incontinence (interventional procedure guidance 5). Current evidence on the safety and efficacy of sacral nerve stimulation for faecal incontinence appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. The procedure should only be performed in specialist units by clinicians with a particular interest in the assessment and treatment of faecal incontinence.# The procedure # Indications Faecal incontinence occurs when a person loses control of their bowel and is unable to retain faeces in the rectum. Faecal incontinence may result from dysfunction of the anal sphincter, which may be due to sphincter damage, spinal injury or a neurological disorder. Faecal incontinence is associated with a high level of physical and social disability. Typically, first-line treatment for faecal incontinence is conservative, such as anti-diarrhoeal medication and pelvic floor muscle training (including biofeedback therapy). In patients for whom conservative treatments have been unsuccessful, surgical alternatives include tightening the sphincter (overlapping sphincteroplasty), creating a new sphincter from the patient's own muscle (for example, dynamic graciloplasty) or implanting an artificial sphincter. Some patients may require colostomy. Sacral nerve stimulation is a surgical treatment option for patients with faecal incontinence. # Outline of the procedure In patients with a weak but structurally intact sphincter, it may be possible to alter sphincter and bowel behaviour using the surrounding nerves and muscles. It involves applying an electric current to one of the sacral nerves via an electrode placed through the corresponding sacral foramen. Commonly, the procedure is tested in each patient over a 2- to 3-week period, with a temporary percutaneous peripheral nerve electrode attached to an external stimulator. If significant benefit is achieved, then the permanent implantable pulse generator can be implanted. # Efficacy This procedure was subject to a systematic review commissioned by the Institute. The systematic review included six case series studies reporting on 266 patients in total. In patients who had permanent implants, complete continence was achieved in 41–75% (19/46–12/16) of patients, whereas 75–100% (3/4–16/16) of patients experienced a decrease of 50% or more in the number of incontinence episodes. There was also evidence to suggest an improvement in the ability to defer defecation after permanent implantation. Patients also reported improvements in both disease-specific and general quality-of-life scores after the procedure. For more details, refer to the Sources of evidence section. # Safety Complications were reported both during the test peripheral nerve evaluation phase and after implantation. Evidence from the systematic review indicated that of the 266 patients receiving test evaluation, 4% (10/266) experienced an adverse event. Fifty-six per cent (149/266) went on to receive permanent implantation. Of the patients who had permanent implants, 13% (19/149) reported adverse events. These included three patients who developed infections requiring device removal, seven patients who had lead migration requiring either relocation (five cases) or removal of the device, and six patients who experienced pain after implantation. Implantation techniques have been modified in recent years, with a view to reducing the occurrence of complications. Andrew DillonChief ExecutiveNovember 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. Fraser C, Glazener C, Grant A et al. Systematic review of the efficacy and safety of sacral nerve stimulation for faecal incontinence. Aberdeen: Review Body for Interventional Procedures; 2004. Commissioned by the National Institute for Clinical Excellence. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It updates and replaces NICE interventional procedure guidance 5. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'This document replaces previous guidance on sacral nerve stimulation for faecal incontinence (interventional procedure guidance 5).\n\nCurrent evidence on the safety and efficacy of sacral nerve stimulation for faecal incontinence appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe procedure should only be performed in specialist units by clinicians with a particular interest in the assessment and treatment of faecal incontinence.', 'The procedure': "# Indications\n\nFaecal incontinence occurs when a person loses control of their bowel and is unable to retain faeces in the rectum. Faecal incontinence may result from dysfunction of the anal sphincter, which may be due to sphincter damage, spinal injury or a neurological disorder.\n\nFaecal incontinence is associated with a high level of physical and social disability.\n\nTypically, first-line treatment for faecal incontinence is conservative, such as anti-diarrhoeal medication and pelvic floor muscle training (including biofeedback therapy). In patients for whom conservative treatments have been unsuccessful, surgical alternatives include tightening the sphincter (overlapping sphincteroplasty), creating a new sphincter from the patient's own muscle (for example, dynamic graciloplasty) or implanting an artificial sphincter. Some patients may require colostomy. Sacral nerve stimulation is a surgical treatment option for patients with faecal incontinence.\n\n# Outline of the procedure\n\nIn patients with a weak but structurally intact sphincter, it may be possible to alter sphincter and bowel behaviour using the surrounding nerves and muscles. It involves applying an electric current to one of the sacral nerves via an electrode placed through the corresponding sacral foramen. Commonly, the procedure is tested in each patient over a 2- to 3-week period, with a temporary percutaneous peripheral nerve electrode attached to an external stimulator. If significant benefit is achieved, then the permanent implantable pulse generator can be implanted.\n\n# Efficacy\n\nThis procedure was subject to a systematic review commissioned by the Institute. The systematic review included six case series studies reporting on 266 patients in total. In patients who had permanent implants, complete continence was achieved in 41–75% (19/46–12/16) of patients, whereas 75–100% (3/4–16/16) of patients experienced a decrease of 50% or more in the number of incontinence episodes. There was also evidence to suggest an improvement in the ability to defer defecation after permanent implantation. Patients also reported improvements in both disease-specific and general quality-of-life scores after the procedure. For more details, refer to the Sources of evidence section.\n\n# Safety\n\nComplications were reported both during the test peripheral nerve evaluation phase and after implantation. Evidence from the systematic review indicated that of the 266 patients receiving test evaluation, 4% (10/266) experienced an adverse event. Fifty-six per cent (149/266) went on to receive permanent implantation. Of the patients who had permanent implants, 13% (19/149) reported adverse events. These included three patients who developed infections requiring device removal, seven patients who had lead migration requiring either relocation (five cases) or removal of the device, and six patients who experienced pain after implantation.\n\nImplantation techniques have been modified in recent years, with a view to reducing the occurrence of complications.\n\nAndrew DillonChief ExecutiveNovember 2004", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\nFraser C, Glazener C, Grant A et al. Systematic review of the efficacy and safety of sacral nerve stimulation for faecal incontinence. Aberdeen: Review Body for Interventional Procedures; 2004. Commissioned by the National Institute for Clinical Excellence.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt updates and replaces NICE interventional procedure guidance 5.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg99
d7e0d391e4fec0b3f7d1781c52a1ba8f3ff3e321	nice	Dental checks: intervals between oral health reviews	Dental checks: intervals between oral health reviews This guideline covers assigning recall intervals between oral health reviews that are appropriate to the needs of individual patients. The guideline takes account of the effect of dental checks on: people’s wellbeing, general health and preventive habits; caries incidence and avoiding restorations; periodontal health and avoiding tooth loss; and avoiding pain and anxiety. It aims to improve or maintain patients’ quality of life and reduce morbidity associated with oral and dental disease. # Introduction Six-monthly dental check-ups have been customary in the General Dental Service in the UK since the inception of the NHS. In recent years there has been significant debate over the timing of recall intervals for dental check-ups, and this has coincided with a move towards making NHS dental services in England and Wales more oriented to prevention and more clinically effective in meeting patients' needs. The Department of Health's strategy document NHS Dentistry: Options for Change (2002) and subsequent legislation are bringing about changes in the organisation of dental services and the way in which oral health is assessed. Under the new arrangements, a comprehensive oral health assessment will be conducted when a patient first visits a dental practice and will involve taking full histories, carrying out thorough dental and head and neck examinations and providing initial preventive advice. The dentist and patient will discuss the findings and agree a personalised care plan and a 'destination' for this journey of care. The dental team and patient will then work through this first personal care plan. After an agreed interval, the patient will return for an oral health review, during which the histories and examination will be updated and any changes in risk factors noted. The dental team will also assess the effectiveness of the treatment and preventive advice provided previously, and will give more advice as necessary. The patient and dentist will discuss the findings of the review and agree the next, refined, personalised care plan and a specific 'destination' for this new journey of care. The purpose of this guideline is to help clinicians assign recall intervals between oral health reviews that are appropriate to the needs of individual patients. The recommendations apply to patients of all ages (both dentate and edentulous) receiving primary care from NHS dental staff in England and Wales. The guideline takes into account the potential of the patient and the dental team to improve or maintain the patient's quality of life and to reduce morbidity associated with oral and dental disease. The recommendations take account of the impact of dental checks on: patients' wellbeing, general health and preventive habits; caries incidence and avoiding restorations; periodontal health and avoiding tooth loss; and avoiding pain and anxiety. This guideline does not cover: recall intervals for scale and polish treatments the prescription and timing of dental radiographs intervals between examinations that are not routine dental recalls; that is, intervals between examinations relating to ongoing courses of treatment emergency dental interventions or intervals between episodes of specialist care. The following guidance is based on the best available evidence. There is evidence relating to risk factors for oral disease and on the effectiveness of dental health education and oral health promotion, and this was used to inform the guideline recommendations. However, the research evidence on many aspects of dental recall intervals was limited, and recommendations were based on the clinical experience of the guideline development group and advice received during the consultation process.# Recommendations People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care. Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding. The recommended interval between oral health reviews should be determined specifically for each patient and tailored to meet his or her needs, on the basis of an assessment of disease levels and risk of or from dental disease. This assessment should integrate the evidence presented in this guideline with the clinical judgement and expertise of the dental team, and should be discussed with the patient. During an oral health review, the dental team (led by the dentist) should ensure that comprehensive histories are taken, examinations are conducted and initial preventive advice is given (see NICE's guideline on oral health promotion: general dental practice). This will allow the dental team and the patient (and/or his or her parent, guardian or carer) to discuss, where appropriate: the effects of oral hygiene, diet, fluoride use, tobacco and alcohol on oral health the risk factors (see the checklist in appendix G of the full guideline) that may influence the patient's oral health, and their implications for deciding the appropriate recall interval the outcome of previous care episodes and the suitability of previously recommended intervals the patient's ability or desire to visit the dentist at the recommended interval the financial costs to the patient of having the oral health review and any subsequent treatments. The interval before the next oral health review should be chosen, either at the end of an oral health review if no further treatment is indicated, or on completion of a specific treatment journey. The recommended shortest and longest intervals between oral health reviews are as follows: The shortest interval between oral health reviews for all patients should be 3 months.A recall interval of less than 3 months is not normally needed for a routine dental recall. A patient may need to be seen more frequently for specific reasons such as disease management, ongoing courses of treatment, emergency dental interventions, or episodes of specialist care, which are outside the scope of an oral health review. The longest interval between oral health reviews for patients younger than 18 years should be 12 months. There is evidence that the rate of progression of dental caries can be more rapid in children and adolescents than in older people, and it seems to be faster in primary teeth than in permanent teeth (see the full guideline). Periodic developmental assessment of the dentition is also required in children.Recall intervals of no longer than 12 months give the opportunity for delivering and reinforcing preventive advice and for raising awareness of the importance of good oral health. This is particularly important in young children, to lay the foundations for life-long dental health. The longest interval between oral health reviews for patients aged 18 years and older should be 24 months. Recall intervals for patients who have repeatedly demonstrated that they can maintain oral health and who are not considered to be at risk of or from oral disease may be extended over time up to an interval of 24 months. Intervals of longer than 24 months are undesirable because they could diminish the professional relationship between dentist and patient, and people's lifestyles may change. For practical reasons, the patient should be assigned a recall interval of 3, 6, 9 or 12 months if he or she is younger than 18 years old, or 3, 6, 9, 12, 15, 18, 21 or 24 months if he or she is aged 18 years or older. The dentist should discuss the recommended recall interval with the patient and record this interval, and the patient's agreement or disagreement with it, in the current record-keeping system. The recall interval should be reviewed again at the next oral health review, to learn from the patient's responses to the oral care provided and the health outcomes achieved. This feedback and the findings of the oral health review should be used to adjust the next recall interval chosen. Patients should be informed that their recommended recall interval may vary over time. The interval may be maintained at the same level if it is achieving its aims. For someone with low disease activity, it may be possible to gradually extend the interval towards the 24‑month maximum period – once the patient and the dental team are confident that this is satisfactory. Patients whose disease activity continues unabated may need a shorter interval and may need more intensive preventive care and closer supervision.Patients should be encouraged to seek advice from a dentist before their next scheduled review if there are any significant changes in their risk factors. They also need to understand that (as is the case with the current 6‑month recall regimen) there is no guarantee that new disease will not develop between recall visits.# Recommendations for research While developing this guideline, the research evidence in a number of areas was found either to be inconclusive or not to exist. Research in the following areas would help in updating this guideline and implementing it in general dental practice: Dental attendance patterns should be examined for changes after the publication of the guideline. After publication of the guideline, information will be needed on whether patients visit the dentist at the agreed interval, and their reasons for this. Research is needed on the long-term clinical and cost effectiveness of one-to-one oral health advice and whether this may depend on: the frequency with which it is delivered the physical or oral health of the patient -ther characteristics of the patient (for example, age, sex, social class, occupation) the medium used to deliver the advice who delivers the advice. Research is needed to examine the effects of varying dental recall intervals on oral health, and on which aspects of the oral health review influence oral health. Research is needed to examine the impact of oral health (relating to gingivitis, caries, periodontal disease and mucosal disease) on quality of life. Research is needed to examine the effects on periodontal health of routine scale and polish treatment (in conjunction with oral hygiene instruction) in different populations. Specifically, research is needed to examine the clinical effectiveness and cost effectiveness of providing this intervention at different time intervals. Research designs will need to accommodate the mix of arrangements (NHS, private and mixed configurations) under which dental primary care is provided.	{'Introduction': "Six-monthly dental check-ups have been customary in the General Dental Service in the UK since the inception of the NHS. In recent years there has been significant debate over the timing of recall intervals for dental check-ups, and this has coincided with a move towards making NHS dental services in England and Wales more oriented to prevention and more clinically effective in meeting patients' needs.\n\nThe Department of Health's strategy document NHS Dentistry: Options for Change (2002) and subsequent legislation are bringing about changes in the organisation of dental services and the way in which oral health is assessed. Under the new arrangements, a comprehensive oral health assessment will be conducted when a patient first visits a dental practice and will involve taking full histories, carrying out thorough dental and head and neck examinations and providing initial preventive advice. The dentist and patient will discuss the findings and agree a personalised care plan and a 'destination' for this journey of care. The dental team and patient will then work through this first personal care plan.\n\nAfter an agreed interval, the patient will return for an oral health review, during which the histories and examination will be updated and any changes in risk factors noted. The dental team will also assess the effectiveness of the treatment and preventive advice provided previously, and will give more advice as necessary. The patient and dentist will discuss the findings of the review and agree the next, refined, personalised care plan and a specific 'destination' for this new journey of care.\n\nThe purpose of this guideline is to help clinicians assign recall intervals between oral health reviews that are appropriate to the needs of individual patients. The recommendations apply to patients of all ages (both dentate and edentulous) receiving primary care from NHS dental staff in England and Wales. The guideline takes into account the potential of the patient and the dental team to improve or maintain the patient's quality of life and to reduce morbidity associated with oral and dental disease.\n\nThe recommendations take account of the impact of dental checks on: patients' wellbeing, general health and preventive habits; caries incidence and avoiding restorations; periodontal health and avoiding tooth loss; and avoiding pain and anxiety.\n\nThis guideline does not cover:\n\nrecall intervals for scale and polish treatments\n\nthe prescription and timing of dental radiographs\n\nintervals between examinations that are not routine dental recalls; that is, intervals between examinations relating to ongoing courses of treatment\n\nemergency dental interventions or intervals between episodes of specialist care.\n\nThe following guidance is based on the best available evidence. There is evidence relating to risk factors for oral disease and on the effectiveness of dental health education and oral health promotion, and this was used to inform the guideline recommendations. However, the research evidence on many aspects of dental recall intervals was limited, and recommendations were based on the clinical experience of the guideline development group and advice received during the consultation process.", 'Recommendations': "People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care.\n\nMaking decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.\n\nThe recommended interval between oral health reviews should be determined specifically for each patient and tailored to meet his or her needs, on the basis of an assessment of disease levels and risk of or from dental disease.\n\nThis assessment should integrate the evidence presented in this guideline with the clinical judgement and expertise of the dental team, and should be discussed with the patient.\n\nDuring an oral health review, the dental team (led by the dentist) should ensure that comprehensive histories are taken, examinations are conducted and initial preventive advice is given (see NICE's guideline on oral health promotion: general dental practice). This will allow the dental team and the patient (and/or his or her parent, guardian or carer) to discuss, where appropriate:\n\nthe effects of oral hygiene, diet, fluoride use, tobacco and alcohol on oral health\n\nthe risk factors (see the checklist in appendix G of the full guideline) that may influence the patient's oral health, and their implications for deciding the appropriate recall interval\n\nthe outcome of previous care episodes and the suitability of previously recommended intervals\n\nthe patient's ability or desire to visit the dentist at the recommended interval\n\nthe financial costs to the patient of having the oral health review and any subsequent treatments.\n\nThe interval before the next oral health review should be chosen, either at the end of an oral health review if no further treatment is indicated, or on completion of a specific treatment journey.\n\nThe recommended shortest and longest intervals between oral health reviews are as follows:\n\nThe shortest interval between oral health reviews for all patients should be 3 months.A recall interval of less than 3\xa0months is not normally needed for a routine dental recall. A patient may need to be seen more frequently for specific reasons such as disease management, ongoing courses of treatment, emergency dental interventions, or episodes of specialist care, which are outside the scope of an oral health review.\n\nThe longest interval between oral health reviews for patients younger than 18\xa0years should be 12\xa0months. There is evidence that the rate of progression of dental caries can be more rapid in children and adolescents than in older people, and it seems to be faster in primary teeth than in permanent teeth (see the full guideline). Periodic developmental assessment of the dentition is also required in children.Recall intervals of no longer than 12\xa0months give the opportunity for delivering and reinforcing preventive advice and for raising awareness of the importance of good oral health. This is particularly important in young children, to lay the foundations for life-long dental health.\n\nThe longest interval between oral health reviews for patients aged 18\xa0years and older should be 24\xa0months. Recall intervals for patients who have repeatedly demonstrated that they can maintain oral health and who are not considered to be at risk of or from oral disease may be extended over time up to an interval of 24\xa0months. Intervals of longer than 24\xa0months are undesirable because they could diminish the professional relationship between dentist and patient, and people's lifestyles may change.\n\nFor practical reasons, the patient should be assigned a recall interval of 3, 6, 9 or 12\xa0months if he or she is younger than 18\xa0years old, or 3, 6, 9, 12, 15, 18, 21 or 24\xa0months if he or she is aged 18\xa0years or older.\n\nThe dentist should discuss the recommended recall interval with the patient and record this interval, and the patient's agreement or disagreement with it, in the current record-keeping system.\n\nThe recall interval should be reviewed again at the next oral health review, to learn from the patient's responses to the oral care provided and the health outcomes achieved. This feedback and the findings of the oral health review should be used to adjust the next recall interval chosen. Patients should be informed that their recommended recall interval may vary over time. The interval may be maintained at the same level if it is achieving its aims. For someone with low disease activity, it may be possible to gradually extend the interval towards the 24‑month maximum period – once the patient and the dental team are confident that this is satisfactory. Patients whose disease activity continues unabated may need a shorter interval and may need more intensive preventive care and closer supervision.Patients should be encouraged to seek advice from a dentist before their next scheduled review if there are any significant changes in their risk factors. They also need to understand that (as is the case with the current 6‑month recall regimen) there is no guarantee that new disease will not develop between recall visits.", 'Recommendations for research': 'While developing this guideline, the research evidence in a number of areas was found either to be inconclusive or not to exist. Research in the following areas would help in updating this guideline and implementing it in general dental practice:\n\nDental attendance patterns should be examined for changes after the publication of the guideline.\n\nAfter publication of the guideline, information will be needed on whether patients visit the dentist at the agreed interval, and their reasons for this.\n\nResearch is needed on the long-term clinical and cost effectiveness of one-to-one oral health advice and whether this may depend on:\n\n\n\nthe frequency with which it is delivered\n\nthe physical or oral health of the patient\n\nother characteristics of the patient (for example, age, sex, social class, occupation)\n\nthe medium used to deliver the advice\n\nwho delivers the advice.\n\n\n\nResearch is needed to examine the effects of varying dental recall intervals on oral health, and on which aspects of the oral health review influence oral health.\n\nResearch is needed to examine the impact of oral health (relating to gingivitis, caries, periodontal disease and mucosal disease) on quality of life.\n\nResearch is needed to examine the effects on periodontal health of routine scale and polish treatment (in conjunction with oral hygiene instruction) in different populations. Specifically, research is needed to examine the clinical effectiveness and cost effectiveness of providing this intervention at different time intervals.\n\nResearch designs will need to accommodate the mix of arrangements (NHS, private and mixed configurations) under which dental primary care is provided.'}	https://www.nice.org.uk/guidance/cg19	This guideline covers assigning recall intervals between oral health reviews that are appropriate to the needs of individual patients. The guideline takes account of the effect of dental checks on: people’s wellbeing, general health and preventive habits; caries incidence and avoiding restorations; periodontal health and avoiding tooth loss; and avoiding pain and anxiety. It aims to improve or maintain patients’ quality of life and reduce morbidity associated with oral and dental disease.
2a38f2a63e1bd1df80fd9fd289ed7766d700d1a7	nice	Radiofrequency valvotomy for pulmonary atresia	Radiofrequency valvotomy for pulmonary atresia # Guidance Current evidence on the safety and efficacy of radiofrequency valvotomy for pulmonary atresia with intact interventricular septum is limited due to the rarity of the condition, but appears adequate to support the use of the procedure for the treatment of seriously ill neonates, provided that normal arrangements are in place for consent, audit and clinical governance. Radiofrequency valvotomy for pulmonary atresia with intact interventricular septum should be performed in carefully selected patients in specialist centres with paediatric cardiac surgery facilities. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database.# The procedure # Indications Radiofrequency valvotomy is used to treat pulmonary atresia, a congenital malformation of the pulmonary valve in which the valve orifice fails to develop. The valve is completely closed, thereby obstructing the outflow of blood from the heart to the lungs. Babies with this type of cyanotic congenital heart disease survive only for the first few days of life. During those first few days, if there is no operation to open the pulmonary valve or to make a shunt between the aorta and the pulmonary arteries, the condition is fatal. The standard treatment for pulmonary atresia is open heart surgery that includes the Fontan procedure (the surgical creation of a right ventricular bypass by directly connecting either the right atrium or the superior or inferior vena cava with the pulmonary artery) and the Blalock-Taussig shunt (a palliative procedure in which a shunt is created to allow blood to pass from the aorta to the pulmonary artery by dividing the left subclavian artery and connecting it to the left pulmonary artery). Further open heart surgery may include open surgical valvotomy. # Outline of the procedure Radiofrequency valvotomy is a minimally invasive cardiac catheterisation procedure that involves creating an opening in the blocked pulmonary valve followed by dilatation using balloon angioplasty. It avoids the need for open surgery but some children will later need a permanent shunt procedure or surgical relief of pulmonary valve obstruction. # Efficacy The evidence was limited to one small nonrandomised comparative study and four small uncontrolled studies. The success rate of the procedure varied between 75% (9/12) and 93% (14/15). The proportion of patients with establishment of a biventricular circulation was reported in four studies. In the comparative study, 63% (12/19) of patients had a biventricular circulation established after radiofrequency valvotomy, compared with 50% (7/14) after surgical valvotomy. In the other three studies, a biventricular circulation was established in between 42% (5/12) and 53% (16/30) of patients. For more details, refer to the Sources of evidence section. One Specialist Advisor commented that proper patient selection was important in order to achieve good clinical outcomes. # Safety In the comparative study, the mortality rate for patients who underwent radiofrequency valvotomy was 16% (3/19), compared with 29% (4/14) for patients who underwent surgical valvotomy. The largest non-comparative study (of 30 patients) reported three postoperative deaths and two late deaths. Other complications reported in the studies included perforation of the pulmonary artery in between 3% (1/30) and 33% (4/12) of patients, and perforation of the right ventricular outflow tract in 17% (3/18) of patients. For more details, refer to the Sources of evidence section. The Specialist Advisors considered the main risks of the procedure to be death, perforation of the heart, cardiac tamponade, cardiac or pulmonary artery perforation/rupture, arrhythmias, infection and multiple organ failure. # Other comments In making its recommendations, the Advisory Committee was influenced by the specialist advice that the procedure is established treatment for severely ill neonates who may otherwise die. Andrew DillonChief ExecutiveOctober 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of radiofrequency valvotomy in pulmonary atresia', March 2003. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication May 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of radiofrequency valvotomy for pulmonary atresia with intact interventricular septum is limited due to the rarity of the condition, but appears adequate to support the use of the procedure for the treatment of seriously ill neonates, provided that normal arrangements are in place for consent, audit and clinical governance.\n\nRadiofrequency valvotomy for pulmonary atresia with intact interventricular septum should be performed in carefully selected patients in specialist centres with paediatric cardiac surgery facilities.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database.', 'The procedure': '# Indications\n\nRadiofrequency valvotomy is used to treat pulmonary atresia, a congenital malformation of the pulmonary valve in which the valve orifice fails to develop. The valve is completely closed, thereby obstructing the outflow of blood from the heart to the lungs. Babies with this type of cyanotic congenital heart disease survive only for the first few days of life. During those first few days, if there is no operation to open the pulmonary valve or to make a shunt between the aorta and the pulmonary arteries, the condition is fatal.\n\nThe standard treatment for pulmonary atresia is open heart surgery that includes the Fontan procedure (the surgical creation of a right ventricular bypass by directly connecting either the right atrium or the superior or inferior vena cava with the pulmonary artery) and the Blalock-Taussig shunt (a palliative procedure in which a shunt is created to allow blood to pass from the aorta to the pulmonary artery by dividing the left subclavian artery and connecting it to the left pulmonary artery). Further open heart surgery may include open surgical valvotomy.\n\n# Outline of the procedure\n\nRadiofrequency valvotomy is a minimally invasive cardiac catheterisation procedure that involves creating an opening in the blocked pulmonary valve followed by dilatation using balloon angioplasty. It avoids the need for open surgery but some children will later need a permanent shunt procedure or surgical relief of pulmonary valve obstruction.\n\n# Efficacy\n\nThe evidence was limited to one small nonrandomised comparative study and four small uncontrolled studies. The success rate of the procedure varied between 75% (9/12) and 93% (14/15). The proportion of patients with establishment of a biventricular circulation was reported in four studies. In the comparative study, 63% (12/19) of patients had a biventricular circulation established after radiofrequency valvotomy, compared with 50% (7/14) after surgical valvotomy. In the other three studies, a biventricular circulation was established in between 42% (5/12) and 53% (16/30) of patients. For more details, refer to the Sources of evidence section.\n\nOne Specialist Advisor commented that proper patient selection was important in order to achieve good clinical outcomes.\n\n# Safety\n\nIn the comparative study, the mortality rate for patients who underwent radiofrequency valvotomy was 16% (3/19), compared with 29% (4/14) for patients who underwent surgical valvotomy. The largest non-comparative study (of 30 patients) reported three postoperative deaths and two late deaths. Other complications reported in the studies included perforation of the pulmonary artery in between 3% (1/30) and 33% (4/12) of patients, and perforation of the right ventricular outflow tract in 17% (3/18) of patients. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered the main risks of the procedure to be death, perforation of the heart, cardiac tamponade, cardiac or pulmonary artery perforation/rupture, arrhythmias, infection and multiple organ failure.\n\n# Other comments\n\nIn making its recommendations, the Advisory Committee was influenced by the specialist advice that the procedure is established treatment for severely ill neonates who may otherwise die.\n\nAndrew DillonChief ExecutiveOctober 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of radiofrequency valvotomy in pulmonary atresia', March 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nMay 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg95
4e06d1383a49809b5039b4da1a94590123e48b40	nice	Endovascular closure of atrial septal defect	Endovascular closure of atrial septal defect The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on endovascular closure of atrial septal defect. # Guidance Current evidence on the safety and efficacy of endovascular closure of atrial septal defect appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. The procedure should be performed in units where there are arrangements for cardiac surgical support in the event of complications. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database.# The procedure # Indications An atrial septal defect is the persistence of a hole (the foramen ovale) in the wall (septum) between the right atrium and left atrium of the heart. The foramen ovale usually closes spontaneously after birth; an atrial septal defect is present when this closure does not occur. In the most common type, called an ostium secundum atrial septal defect, the septum between the atria fails to form properly during foetal development, resulting in a permanent hole. An atrial septal defect allows blood to flow from the left atrium to the right atrium, thereby increasing the flow of blood to the lungs. This is known as a shunt. Patients with atrial septal defects are usually asymptomatic through infancy and childhood. Symptoms such as exertional dyspnoea, fatigue, palpitations and syncope can occur and increasing age carries a higher risk of stroke. Some patients may develop congestive heart failure. Not all atrial septal defects require treatment, but it is generally agreed that larger defects and those associated with either symptoms or significant enlargement of the heart should be closed electively. Conventional surgery for atrial septal defect is performed through an incision in the front of the chest. After establishing cardiopulmonary bypass, the right atrium is opened to gain access to the interatrial septum. The defect is then repaired using a patch or stitches. Patients usually stay in hospital for several days after the operation. # Outline of the procedure Endovascular closure of an atrial septal defect involves making a small incision in the groin to introduce a guidewire and delivery sheath into the femoral vein. An occluder device is then introduced through the delivery sheath on a semi-rigid cable and expanded within the atrial septal defect to close it. Echocardiography and fluoroscopic guidance are used to determine the size and position of the defect and to place the occlude device. A balloon may be used to measure the diameter of the defect. Patients can usually go home the next day. Small residual shunts after the procedure often resolve as endothelial tissue grows over and around the device. The claimed advantages compared with open surgery are shorter hospital stay, earlier return to normal activities and fewer complications. # Efficacy Three non-randomised controlled studies reported successful closure rates immediately after the endovascular procedure of 96% (423/442), 98% (60/61) and 97% (28/29), compared with rates of 100% (154/154), 98% (60/61) and 100% (64/64), respectively, for conventional surgery. A large case series of 3460 patients reported that 97% (3301/3391) of atrial septal defects were successfully closed immediately after the procedure. Of the 4% (147/3460) of patients followed up for 2 years in this study, all maintained successful closure. A further case series reported that 1% (4/314) of patients had a significant residual shunt immediately after the procedure and 93% (99/107) of patients had a successful closure 1 year after the procedure. For more details, refer to the Sources of evidence section. The Specialist Advisors noted that a small proportion of patients might be left with a residual shunt. # Safety The reported complication rates were low. They included malpositioning of the device, requiring endovascular or surgical retrieval 1% (6/417) to 5% (16/334); arrhythmia 0.4% (2/459) to 5% (3/61); embolisation of the device 0.4% (14/3460) to 4% (14/334); thrombus formation 0.4% (1/258) to 3% (1/37); brachial plexus injury 3% (1/39); right iliac vein dissection 0.6% (1/159); stroke 0.1% (5/3460) to 0.3% (1/334); cardiac tamponade 0.1% (2/3460); cardiac perforation 0.03% (1/3460); and endocarditis 0.03% (1/3460). For more details, refer to the Sources of evidence section. The Specialist Advisors listed arrhythmias, stroke, device embolisation and cardiac tamponade as potential adverse effects of the procedure. # Other comments There is the potential for long-term adverse effects and clinicians should report these to the Medicines and Healthcare products Regulatory Agency (MHRA). These recommendations were based on evidence on the use of the Amplatzer®, CardioSEAL®, STARFlex® and Helex® devices for the endovascular closure of atrial septal defect. The Institute may review the procedure if further data relating to other devices become available. Andrew DillonChief ExecutiveOctober 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of endovascular closure of atrial septal defect', March 2004. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication May 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of endovascular closure of atrial septal defect appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe procedure should be performed in units where there are arrangements for cardiac surgical support in the event of complications.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database.', 'The procedure': '# Indications\n\nAn atrial septal defect is the persistence of a hole (the foramen ovale) in the wall (septum) between the right atrium and left atrium of the heart. The foramen ovale usually closes spontaneously after birth; an atrial septal defect is present when this closure does not occur. In the most common type, called an ostium secundum atrial septal defect, the septum between the atria fails to form properly during foetal development, resulting in a permanent hole. An atrial septal defect allows blood to flow from the left atrium to the right atrium, thereby increasing the flow of blood to the lungs. This is known as a shunt. Patients with atrial septal defects are usually asymptomatic through infancy and childhood. Symptoms such as exertional dyspnoea, fatigue, palpitations and syncope can occur and increasing age carries a higher risk of stroke. Some patients may develop congestive heart failure.\n\nNot all atrial septal defects require treatment, but it is generally agreed that larger defects and those associated with either symptoms or significant enlargement of the heart should be closed electively. Conventional surgery for atrial septal defect is performed through an incision in the front of the chest. After establishing cardiopulmonary bypass, the right atrium is opened to gain access to the interatrial septum. The defect is then repaired using a patch or stitches. Patients usually stay in hospital for several days after the operation.\n\n# Outline of the procedure\n\nEndovascular closure of an atrial septal defect involves making a small incision in the groin to introduce a guidewire and delivery sheath into the femoral vein. An occluder device is then introduced through the delivery sheath on a semi-rigid cable and expanded within the atrial septal defect to close it. Echocardiography and fluoroscopic guidance are used to determine the size and position of the defect and to place the occlude device. A balloon may be used to measure the diameter of the defect. Patients can usually go home the next day. Small residual shunts after the procedure often resolve as endothelial tissue grows over and around the device. The claimed advantages compared with open surgery are shorter hospital stay, earlier return to normal activities and fewer complications.\n\n# Efficacy\n\nThree non-randomised controlled studies reported successful closure rates immediately after the endovascular procedure of 96% (423/442), 98% (60/61) and 97% (28/29), compared with rates of 100% (154/154), 98% (60/61) and 100% (64/64), respectively, for conventional surgery. A large case series of 3460 patients reported that 97% (3301/3391) of atrial septal defects were successfully closed immediately after the procedure. Of the 4% (147/3460) of patients followed up for 2 years in this study, all maintained successful closure. A further case series reported that 1% (4/314) of patients had a significant residual shunt immediately after the procedure and 93% (99/107) of patients had a successful closure 1 year after the procedure. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors noted that a small proportion of patients might be left with a residual shunt.\n\n# Safety\n\nThe reported complication rates were low. They included malpositioning of the device, requiring endovascular or surgical retrieval 1% (6/417) to 5% (16/334); arrhythmia 0.4% (2/459) to 5% (3/61); embolisation of the device 0.4% (14/3460) to 4% (14/334); thrombus formation 0.4% (1/258) to 3% (1/37); brachial plexus injury 3% (1/39); right iliac vein dissection 0.6% (1/159); stroke 0.1% (5/3460) to 0.3% (1/334); cardiac tamponade 0.1% (2/3460); cardiac perforation 0.03% (1/3460); and endocarditis 0.03% (1/3460). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors listed arrhythmias, stroke, device embolisation and cardiac tamponade as potential adverse effects of the procedure.\n\n# Other comments\n\nThere is the potential for long-term adverse effects and clinicians should report these to the Medicines and Healthcare products Regulatory Agency (MHRA).\n\nThese recommendations were based on evidence on the use of the Amplatzer®, CardioSEAL®, STARFlex® and Helex® devices for the endovascular closure of atrial septal defect. The Institute may review the procedure if further data relating to other devices become available.\n\nAndrew DillonChief ExecutiveOctober 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of endovascular closure of atrial septal defect', March 2004.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nMay 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg96	The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on endovascular closure of atrial septal defect.
9400c9d54fda645e5e6b42b5f84a954503468b0b	nice	Endovascular closure of patent ductus arteriosus	Endovascular closure of patent ductus arteriosus The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on endovascular closure of patent ductus arteriosus. # Guidance Current evidence on the safety and efficacy of endovascular closure of patent ductus arteriosus (PDA) appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. The procedure should be performed in units where there are arrangements for cardiac surgical support in the event of complications. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database.# The procedure # Indications The ductus arteriosus is a normal vessel in the fetus that connects the pulmonary artery and the aorta. It allows the fetal blood flow to bypass the lungs, which are not used in utero. The ductus arteriosus usually closes at or shortly after birth. Sometimes it fails to close on its own; this is called a patent (or persistent) ductus arteriosus. Blood can then pass from the aorta into the pulmonary artery, exposing the lungs to increased blood flow and pressure. A large PDA may cause symptoms such as poor weight gain and breathlessness. Without medical treatment, blood vessels in the lung may eventually become damaged by the raised blood pressure. This puts strain on the heart and can lead to heart failure. Persistent ductus arteriosus is also associated with an increased risk of endocarditis, a life-threatening infection of the lining of the heart chambers and valves. Open surgery is the standard treatment. Access to the heart is gained via an incision in the chest and a stitch and/or clip is placed around both ends of the ductus arteriosus (ligation), which is then cut in half if there is enough length (ligation and division). # Outline of the procedure The endovascular procedure involves passing a catheter through a vein or artery into the heart. Pressure measurements and angiograms may be performed to assess the size and shape of the ductus. An occlusion device is then introduced into the ductus through the catheter under X-ray guidance. The choice of device depends largely on the size of the PDA. Coils are suitable for closing PDAs of small to moderate size. Other occlusion devices are used to close larger PDAs. Small residual shunts after the procedure often resolve as endothelial tissue grows over and around the device. # Efficacy Three non-randomised controlled studies reported efficacy data. In two of them, immediate occlusion was reported in 68% (71/105) and 77% (23/30) of patients treated with endovascular closure, and in 89% (8/9) and 96% (140/146) of patients treated with open surgery. The third study reported that 94% (93/99) of patients treated with endovascular closure had a successful outcome immediately after the procedure, compared with 99% (109/110) of patients treated with open surgery. The four case series, with a total of 2035 patients, reported rates of immediate complete occlusion between 44% (90/205) and 98% (214/218) following endovascular closure. In all studies, occlusion rates after a period of follow-up were higher than immediately after the procedure. In one case series of 1258 patients, the occlusion rate was 96% at 2-year follow-up compared with an immediate occlusion rate of 59%. For more details, refer to the Sources of evidence section. The Specialist Advisors noted that a small proportion of patients would have a residual shunt. # Safety The most commonly reported complications were haemolysis (most commonly mild to moderate) and embolisation of the device. Rates of haemolysis varied from 0.3% (1/316) to 9% (3/34), and rates of embolisation varied from 0.6% (2/316) to 7% (7/105). A study of 316 patients reported one death as a result of the procedure. For more details, refer to the Sources of evidence section. The Specialist Advisors considered that device embolisation, haemolysis, vascular injury and death were potential adverse events. # Other comments There is a potential for long-term adverse effects and clinicians should report these to the Medicines and Healthcare products Regulatory Agency (MHRA). These recommendations were based on evidence on the use of the Amplatzer® device and coil embolisation for patent (or persistent) ductus arteriosus. The Institute may review the procedure if further data relating to other devices become available. Andrew DillonChief ExecutiveOctober 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of endovascular closure of patent ductus arteriosus', March 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication May 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of endovascular closure of patent ductus arteriosus (PDA) appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe procedure should be performed in units where there are arrangements for cardiac surgical support in the event of complications.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database.', 'The procedure': '# Indications\n\nThe ductus arteriosus is a normal vessel in the fetus that connects the pulmonary artery and the aorta. It allows the fetal blood flow to bypass the lungs, which are not used in utero. The ductus arteriosus usually closes at or shortly after birth. Sometimes it fails to close on its own; this is called a patent (or persistent) ductus arteriosus. Blood can then pass from the aorta into the pulmonary artery, exposing the lungs to increased blood flow and pressure. A large PDA may cause symptoms such as poor weight gain and breathlessness. Without medical treatment, blood vessels in the lung may eventually become damaged by the raised blood pressure. This puts strain on the heart and can lead to heart failure. Persistent ductus arteriosus is also associated with an increased risk of endocarditis, a life-threatening infection of the lining of the heart chambers and valves.\n\nOpen surgery is the standard treatment. Access to the heart is gained via an incision in the chest and a stitch and/or clip is placed around both ends of the ductus arteriosus (ligation), which is then cut in half if there is enough length (ligation and division).\n\n# Outline of the procedure\n\nThe endovascular procedure involves passing a catheter through a vein or artery into the heart. Pressure measurements and angiograms may be performed to assess the size and shape of the ductus. An occlusion device is then introduced into the ductus through the catheter under X-ray guidance. The choice of device depends largely on the size of the PDA. Coils are suitable for closing PDAs of small to moderate size. Other occlusion devices are used to close larger PDAs. Small residual shunts after the procedure often resolve as endothelial tissue grows over and around the device.\n\n# Efficacy\n\nThree non-randomised controlled studies reported efficacy data. In two of them, immediate occlusion was reported in 68% (71/105) and 77% (23/30) of patients treated with endovascular closure, and in 89% (8/9) and 96% (140/146) of patients treated with open surgery. The third study reported that 94% (93/99) of patients treated with endovascular closure had a successful outcome immediately after the procedure, compared with 99% (109/110) of patients treated with open surgery. The four case series, with a total of 2035 patients, reported rates of immediate complete occlusion between 44% (90/205) and 98% (214/218) following endovascular closure. In all studies, occlusion rates after a period of follow-up were higher than immediately after the procedure. In one case series of 1258 patients, the occlusion rate was 96% at 2-year follow-up compared with an immediate occlusion rate of 59%. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors noted that a small proportion of patients would have a residual shunt.\n\n# Safety\n\nThe most commonly reported complications were haemolysis (most commonly mild to moderate) and embolisation of the device. Rates of haemolysis varied from 0.3% (1/316) to 9% (3/34), and rates of embolisation varied from 0.6% (2/316) to 7% (7/105). A study of 316 patients reported one death as a result of the procedure. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered that device embolisation, haemolysis, vascular injury and death were potential adverse events.\n\n# Other comments\n\nThere is a potential for long-term adverse effects and clinicians should report these to the Medicines and Healthcare products Regulatory Agency (MHRA).\n\nThese recommendations were based on evidence on the use of the Amplatzer® device and coil embolisation for patent (or persistent) ductus arteriosus. The Institute may review the procedure if further data relating to other devices become available.\n\nAndrew DillonChief ExecutiveOctober 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of endovascular closure of patent ductus arteriosus', March 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nMay 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg97	The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on endovascular closure of patent ductus arteriosus.
d16e92ddd23f22cc5a1d85c243ed9fdfeb733cea	nice	Intraoperative fluorescence angiography for the evaluation of coronary artery bypass graft patency	Intraoperative fluorescence angiography for the evaluation of coronary artery bypass graft patency The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on intraoperative flourescence angiography in coronary artery bypass grafting. # Guidance Current evidence on intraoperative fluorescence angiography suggests that the procedure is safe enough for routine use in the evaluation of coronary artery bypass graft patency. There is limited evidence on the diagnostic utility (that is, the extent to which knowledge of its results improves patients' outcomes) of this procedure, and clinicians should therefore audit and review the clinical value of intraoperative fluorescence angiography in all patients having the investigation. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Coronary artery bypass grafting is one of the most common cardiac surgical interventions. In this procedure, a section of vessel from another part of the body is used to reroute (bypass) blood around a blocked coronary artery and improve blood flow to the heart. Early blockage of the graft and poor blood flow may be a significant cause of morbidity and mortality in patients who have undergone coronary artery bypass grafting. Several techniques are used intraoperatively to assess graft patency. These include digital palpation, electromagnetic flow measurement, Doppler studies, and conventional and thermal coronary angiography techniques. A limitation with many of the imaging techniques is that they provide poor resolution and definition of the grafts. # Outline of the procedure Intraoperative fluorescence angiography allows confirmation of the location of the coronary arteries and assessment of bypass graft function during coronary artery bypass procedures. The intraoperative fluorescence imaging system consists of a video camera and a laser diode that emits monochromatic light. The camera, guided by a range-detector diode, is positioned a safe distance above the heart. A small amount of indocyanine green (ICG) dye is then administered as a central venous injection. This dye fluoresces when illuminated using laser energy and the images are recorded digitally. Currently the technique is only semiquantitative, in that it permits assessment of graft flow as 'excellent', 'satisfactory' or 'poor' – it cannot provide an exact measure of graft flow. The penetrating depth of the laser beam is only around 1 mm, limiting the use of this technique to certain grafts. For more details, refer to the Sources of evidence section. # Efficacy The evidence on efficacy is based on four case series studies, with three studies reporting on clinically relevant results. In one study, intraoperative graft patency was assessed in 200 patients: graft patency was confirmed in 192 patients (96%), and the additional information provided by the procedure resulted in graft revision of these eight patients. Similar results were reported in two other studies with 1.4% (4/290) to 3.7% (4/107) of grafts revised after the procedure. No other outcomes were reported. For more details, refer to the Sources of evidence section. One Specialist Advisor considered there to be too little information available regarding efficacy. # Safety Complications associated with this procedure appear to be uncommon. There were no reports of adverse events associated with the use of the ICG dye in evaluating the patency of coronary bypass grafts. Six additional papers were identified that described complications following the administration of ICG dye for indications other than coronary graft patency. Most of these were reports of patients developing anaphylactoid reactions, with an incidence ranging from 0.02% to 0.3%. For more details, refer to the Sources of evidence section. One Specialist Advisor stated that anaphylactic/allergic reactions might occur very rarely as a result of this procedure. Andrew DillonChief ExecutiveOctober 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedures overview of intraoperative fluorescence angiography for the evaluation of coronary artery bypass graft patency', October 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on intraoperative fluorescence angiography suggests that the procedure is safe enough for routine use in the evaluation of coronary artery bypass graft patency.\n\nThere is limited evidence on the diagnostic utility (that is, the extent to which knowledge of its results improves patients' outcomes) of this procedure, and clinicians should therefore audit and review the clinical value of intraoperative fluorescence angiography in all patients having the investigation. The Institute may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nCoronary artery bypass grafting is one of the most common cardiac surgical interventions. In this procedure, a section of vessel from another part of the body is used to reroute (bypass) blood around a blocked coronary artery and improve blood flow to the heart. Early blockage of the graft and poor blood flow may be a significant cause of morbidity and mortality in patients who have undergone coronary artery bypass grafting.\n\nSeveral techniques are used intraoperatively to assess graft patency. These include digital palpation, electromagnetic flow measurement, Doppler studies, and conventional and thermal coronary angiography techniques. A limitation with many of the imaging techniques is that they provide poor resolution and definition of the grafts.\n\n# Outline of the procedure\n\nIntraoperative fluorescence angiography allows confirmation of the location of the coronary arteries and assessment of bypass graft function during coronary artery bypass procedures. The intraoperative fluorescence imaging system consists of a video camera and a laser diode that emits monochromatic light. The camera, guided by a range-detector diode, is positioned a safe distance above the heart. A small amount of indocyanine green (ICG) dye is then administered as a central venous injection. This dye fluoresces when illuminated using laser energy and the images are recorded digitally. Currently the technique is only semiquantitative, in that it permits assessment of graft flow as 'excellent', 'satisfactory' or 'poor' – it cannot provide an exact measure of graft flow. The penetrating depth of the laser beam is only around 1 mm, limiting the use of this technique to certain grafts. For more details, refer to the Sources of evidence section.\n\n# Efficacy\n\nThe evidence on efficacy is based on four case series studies, with three studies reporting on clinically relevant results. In one study, intraoperative graft patency was assessed in 200 patients: graft patency was confirmed in 192 patients (96%), and the additional information provided by the procedure resulted in graft revision of these eight patients. Similar results were reported in two other studies with 1.4% (4/290) to 3.7% (4/107) of grafts revised after the procedure. No other outcomes were reported. For more details, refer to the Sources of evidence section.\n\nOne Specialist Advisor considered there to be too little information available regarding efficacy.\n\n# Safety\n\nComplications associated with this procedure appear to be uncommon. There were no reports of adverse events associated with the use of the ICG dye in evaluating the patency of coronary bypass grafts. Six additional papers were identified that described complications following the administration of ICG dye for indications other than coronary graft patency. Most of these were reports of patients developing anaphylactoid reactions, with an incidence ranging from 0.02% to 0.3%. For more details, refer to the Sources of evidence section.\n\nOne Specialist Advisor stated that anaphylactic/allergic reactions might occur very rarely as a result of this procedure.\n\nAndrew DillonChief ExecutiveOctober 2004", 'Further information ': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedures overview of intraoperative fluorescence angiography for the evaluation of coronary artery bypass graft patency', October 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg98	The National Institute for Health and Clinical Excellence (NICE) has issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on intraoperative flourescence angiography in coronary artery bypass grafting.
9d9440386ff2cb91dd741c805bb94c4d69f2521f	nice	Laparoscopic surgery for inguinal hernia repair	Laparoscopic surgery for inguinal hernia repair Evidence-based recommendations on laparoscopic surgery for treating inguinal hernia. # Guidance This guidance replaces 'Laparoscopic surgery for hernia' (NICE Technology Appraisal Guidance 18) issued in January 2001. For details, see 'About this guidance'. Laparoscopic surgery is recommended as one of the treatment options for the repair of inguinal hernia. To enable patients to choose between open and laparoscopic surgery (either by the transabdominal preperitoneal or by the totally extraperitoneal procedure), they should be fully informed of all of the risks (for example, immediate serious complications, postoperative pain/numbness and long-term recurrence rates) and benefits associated with each of the three procedures. In particular, the following points should be considered in discussions between the patient and the surgeon: the individual's suitability for general anaesthesia the nature of the presenting hernia (that is, primary repair, recurrent hernia or bilateral hernia) the suitability of the particular hernia for a laparoscopic or an open approach the experience of the surgeon in the three techniques. Laparoscopic surgery for inguinal hernia repair by TAPP or TEP should only be performed by appropriately trained surgeons who regularly carry out the procedure.# Clinical need and practice An inguinal hernia is a protrusion of a sac of peritoneum (often containing intestine or other abdominal contents) through a weakness in the abdominal wall in the groin. It usually presents as a lump, with or without some discomfort that may limit daily activities and the ability to work. Around 98% of inguinal hernias are found in men because of the vulnerability of the male anatomy to the formation of hernias in this region. Inguinal hernias can occasionally be life-threatening if the bowel within the peritoneal sac strangulates and/or becomes obstructed. In England, there were approximately 70,000 surgical repairs of inguinal hernia in 2001/02, affecting 0.14% of the population and utilising over 100,000 NHS bed-days of hospital resources. Of these procedures, 62,969 were for the repair of primary hernias and 4939 for the repair of recurrent hernias. Surgical repair (herniorraphy) is undertaken in most individuals presenting with inguinal hernia in order to close the defect, alleviate symptoms of discomfort, prevent serious complications (that is, obstruction or strangulation of the bowel) and reduce the risk of recurrence. Most hernia repairs are undertaken as elective procedures. However, 4.8% of primary repairs and 8.6% of recurrent hernias present as an emergency with a complication. Some individuals present with bilateral hernias, which may be repaired during the same operation or at a later date, and up to 30% of people with a primary unilateral hernia subsequently develop a hernia on the opposite side. Traditional methods of open repair (for example, the Bassini method), which repair the hernia defect by suturing, have not changed significantly since their introduction in the late 19th century. Recently, the availability of prosthetic meshes has led to an increase in the number of 'tension-free' methods of reinforcing the inguinal region. Open mesh methods of repair are classified as open flat mesh (OFM; for example, the Lichtenstein method), open preperitoneal mesh (OPPM; for example, the Stoppa and Nyhus methods) and open plug and mesh repair (OPM; for example, the Rutkow method). Open methods of hernia repair are associated with postoperative pain and numbness because of the large inguinal incision. OFM repairs are thought to be the principal surgical method of hernia repair in the UK.# The technology Laparoscopic surgery is a minimal-access technique that allows the hernia repair to be undertaken without the need to open the abdominal wall. Small incisions are made for the laparoscope and operating instruments, and synthetic mesh is usually used to close the hernia and prevent recurrence. There are two main approaches for the laparoscopic repair of inguinal hernias. Transabdominal preperitoneal (TAPP) repair involves access to the hernia through the peritoneal cavity. Mesh is inserted through the peritoneum and placed over all potential hernia sites in the inguinal region. The peritoneum is then closed above the mesh. Totally extraperitoneal (TEP) repair is the newer laparoscopic technique, in which the hernia site is accessed via the preperitoneal plane without entering the peritoneal cavity. TEP repair is considered to be technically more difficult than the TAPP technique, but it may reduce the risk of damage to intra-abdominal organs. The surgical approach to inguinal hernia repair is the main focus of this appraisal; other issues, such as comparisons between TAPP and TEP and the use of laparoscopic surgery in special subgroups (for example, bilateral or recurrent hernia), are subsidiary considerations. The potential benefits of using a laparoscopic approach include reduced postoperative pain, earlier return to normal activities and a reduction in long-term pain and numbness. The repair of bilateral hernias (including occult hernias detected during contralateral inspection at the time of a unilateral repair) may be undertaken during the same operation. Laparoscopic surgery is associated with additional costs, for the endoscopy system (video unit, monitor, endoscope and CO2 insufflator) and instruments (staplers, diathermy scissors or ports), although these may be reusable. The cost of laparoscopic surgery is highly dependent on whether disposable or reusable equipment is used.# Evidence and interpretation The Appraisal Committee (Appendix A) considered evidence from a number of sources (Appendix B). # Clinical effectiveness Outcomes of interest, against which the effectiveness of laparoscopic and open surgery were assessed, were primary outcomes of recurrence and persistent pain, and secondary outcomes of the rate of complications and persistent numbness, the duration of the operation, length of hospital stay, time to return to normal activities and quality of life. A systematic review of the literature identified 37 randomised controlled trials (RCTs) that compared laparoscopic with open mesh repair of inguinal hernias in a total of 5560 participants. The effectiveness of laparoscopic surgery compared with different methods of open surgery (OFM, OPPM and OPM) was presented separately for the TAPP and TEP laparoscopic methods of repair. The best available data (individual patient data, or aggregate data from studies) were used to generate a meta-analysis of the effectiveness of TAPP and TEP procedures for different outcomes of effectiveness. Laparoscopic surgery was associated with a statistically significant increase in operation time compared with open methods of hernia repair. Meta-analysis of 16 RCTs of TAPP repair demonstrated an overall increase of 13.33 minutes (95% CI 12.08 to 14.57) compared with open repair. Meta-analysis of eight RCTs of TEP repair demonstrated an overall increase of 7.89 minutes (95% CI 6.22 to 9.57) compared with open repair. Laparoscopic surgery was associated with a significantly shorter time to return to usual activities in all of the studies that measured this outcome. Meta-analysis of seven RCTs of TAPP repair reported a hazard ratio (HR) of 0.66 (95% CI 0.58 to 0.75; p < 0.00001), corresponding to a return to normal activities approximately 3 days earlier than after open repair. Meta-analysis of five RCTs of TEP repair reported an HR of 0.49 (95% CI 0.42 to 0.56; p < 0.00001), approximating to a return to usual activities 4 days earlier than after open repair. Both TAPP and TEP procedures demonstrated a statistically significant reduction in persistent numbness compared with open repair. Meta-analysis of eight RCTs comparing TAPP and open repair reported a relative risk (RR) of numbness of 0.26 (95% CI 0.17 to 0.40; p < 0.00001) in favour of TAPP repair. Meta-analysis of four RCTs comparing TEP with open repair reported an RR of 0.67 (95% CI 0.53 to 0.86; p < 0.002) in favour of TEP. One trial (n = 160) that randomised patients to TAPP or OPM repair reported no significant difference (RR 1.00, 95% CI 0.06 to 15.71 for TAPP) between the two techniques. Another trial that randomised 254 patients to TEP or OPM repair reported no significant difference (RR 2.57, 95% CI 0.11 to 62.38) between the two techniques. One RCT of TAPP compared with open repair showed that the reduction in numbness was maintained at 5-year follow-up (3% persistent numbness with TAPP compared with 23% with OFM repair). Overall, there were fewer cases of persistent pain at 1 year post-operation after laparoscopic repair, compared with open repair, in both TAPP and TEP studies. Meta-analysis of eight RCTs of TAPP repair reported an RR of 0.72 (95% CI 0.58 to 0.88; p = 0.001) in favour of TAPP. Meta-analysis of four RCTs of TEP repair reported an RR of 0.77 (95% CI 0.64 to 0.92; p = 0.004) in favour of TEP repair. One RCT of TAPP compared with open repair showed that the reduction in pain was maintained at 5-year follow-up (2% persistent pain with TAPP compared with 10% with OFM repair). The rates of recurrence were similar for laparoscopic and open repair. Meta-analysis of 15 TAPP RCTs reported a total of 26 recurrences out of 1052 TAPP procedures (2.5%) compared with 22 recurrences out of 1062 open repair procedures (2.1%; RR 1.18, 95% CI 0.69 to 2.02). Thirteen RCTs of TEP repair reported a total of 23 recurrences out of 1007 TEP repairs (2.3%), compared with 13 recurrences out of 1002 open repair procedures (1.3%; RR 1.61, 95% CI 0.87 to 2.98). A number of studies reported the incidence of adverse events (complications such as haematoma, seroma, wound-related infection, mesh infection, vascular or visceral injuries and port-site hernia). Laparoscopic repair (both TAPP and TEP) was associated with fewer cases of wound-related infection and haematoma. However, TAPP repair was associated with a higher incidence of vascular and visceral injuries compared with open repair (0.13% vascular injuries with TAPP compared with 0% with TEP and open repair; 0.79% visceral injuries with TAPP compared with 0.16% with TEP and 0.14% with open repair). One RCT randomised 52 patients with unilateral inguinal hernia to TAPP (n=28) or TEP (n=24) repair. There were no statistically significant differences between the procedures in terms of the duration of operation, intra-operative complications, incidence of haematoma, recurrence at 3-month follow-up, or time to return to usual activities. There were no direct comparisons of TAPP and TEP methods of laparoscopic repair in patients with bilateral or recurrent hernia. Trials that evaluated the effectiveness of laparoscopic surgery compared with various forms of open surgery (OFM, OPPM and OPM) in the repair of recurrent inguinal hernias (six trials of TAPP and five trials of TEP) and bilateral inguinal hernias (six trials of TAPP and six trials of TEP) were consistent with the overall results for primary surgery of unilateral inguinal hernias. The Assessment Group evaluated the effect of surgeons' experience on the duration of operation for laparoscopic repair (the 'learning effect'). Inexperienced surgeons (up to 20 procedures) were estimated to perform TAPP procedures in 70 minutes and TEP procedures in 95 minutes, compared with experienced surgeons, who were estimated to perform TAPP procedures in 40 minutes and TEP procedures in 55 minutes. A recent study, published after the Assessment Group's initial review, randomised 2164 patients to laparoscopic surgery (10% TAPP, 90% TEP) or to OFM repair. Many of the results of this study were broadly consistent with the findings of the systematic review and did not affect the pooled results when they were incorporated into meta-analysis. This study reported a statistically significant increase in the recurrence rate with laparoscopic surgery (10.1% for TAPP and TEP combined compared with 4.9% after open repair at 2-year follow up, odds ratio 2.2, 95% CI 1.5 to 3.2). When the recurrence rates from the recent study were incorporated into meta-analysis of TEP compared with OFM repair, the RR of recurrence associated with laparoscopic surgery was increased from 1.61 (95% CI 0.57 to 4.60), in the original report, to 2.0 (95% CI 1.43 to 2.81). The incidence of serious complications was also significantly higher with laparoscopic repair (1.1%; TAPP and TEP combined) compared with open repair (0.1%; OR 11.2, 95% CI 1.3 to 1.7), although this had little effect on the results when incorporated into the meta-analysis. This study also reported a reduction in persistent pain after laparoscopic compared with open repairs (9.8% after laparoscopic surgery compared with 14.3% after open repair). # Cost effectiveness The literature review identified seven economic evaluations of laparoscopic surgery for inguinal hernia repair – three based on economic models and four based on primary studies. Only two studies (submitted by Ethicon Endo-Surgery and BARD Ltd) were relevant to the UK setting. Ethicon Endo-Surgery provided a re-analysis of data from the MRC Laparoscopic Groin Hernia Trial, taking into consideration the repair of occult bilateral hernias. This model was based on the assumption that bilateral repairs in 30% of people with occult hernias would prevent the need for subsequent operation, and reduced the incremental cost effectiveness ratio (ICER) for laparoscopic surgery from £55,549 per quality-adjusted life year (QALY), as reported in the MRC Laparoscopic Groin Hernia Trial, to £15,000 per QALY. However, the model did not take into account the possibility that some people with occult hernias would not develop a clinically significant hernia. The BARD submission compared the cost effectiveness of the Perfix plug (used in OPM repairs) with that of laparoscopic surgery on the basis of data presented in the previous guidance, issued in 2001 (see Section 8). BARD estimated that open plug and mesh repairs may be cost saving on the basis of assumptions that the additional device cost may be offset by reductions in the recurrence rate (0.5% Perfix plug compared with 2.2% with laparoscopic surgery reported in the previous guidance) and an increase in the number of perfix plug repairs undertaken as less costly day cases (91% perfix plug and 60% laparoscopic repairs undertaken as day cases). The Assessment Group developed a Markov model that updates the paper by Vale l, Grant A and McCormack K (unpublished data 2003). The cost and outcome of various laparoscopic (TAPP and TEP) and open (OFM, OPPM and OPM) techniques were assessed in 1-year cycles over 5- and 25-year time horizons. All individuals entered the model at the point of initial hernia repair. In the first year, survivors were assumed to undergo a 3-month period of convalescence and then to return to full health. In subsequent years, individuals could be in a health state of no recurrence (with or without persistent pain or numbness), recurrent hernia proceeding to re-operation, recurrence without re-operation (at risk of emergency surgery for complications), or death (operative and all-cause mortality). Inputs to the economic model on the costs and EQ5D utility estimates for the different health states were based on data from the MRC Laparoscopic Groin Hernia Trial. Theatre costs (£6.40 per minute) and in-hospital costs (£236 per day) were similar for open and laparoscopic procedures. The additional equipment and consumable costs of laparoscopic surgery were £167 per procedure when using predominantly reusable equipment (assuming all reusable devices are used on average 250 times a year for 5 years), or £788 per procedure when predominantly disposable equipment is used. Baseline estimates for operation length, hospital stay, operative mortality, recurrence, re-operation, persistent pain and numbness, time away from usual activities and health state utilities were taken from the best available data identified during this systematic review. Relative differences in the effectiveness of the different methods of open and laparoscopic repair were based on the meta-analysis results for the various outcomes, which were applied to these baseline parameters. Probabilities, costs and utilities were not considered to be fixed but were assigned a probability distribution to reflect uncertainty about their values. The same annual risk of recurrence, pain, numbness and relative effect sizes was used for primary and subsequent procedures. A constant annual risk for persistent pain, numbness and recurrence was assumed when extrapolating from years 6 to 25 of the model. The results from the model showed that laparoscopic surgery (using reusable equipment) was associated with an increased cost of between £100 and £400 per procedure. Also, QALY differences between all of the techniques were small. Incremental analysis found the OPM method to be the most cost-effective method of open repair, driven by the duration of operation and hospital stay, which was the shortest with this procedure. However, when the same duration of operation and of hospital stay were assumed for all open procedures, the costs of OPM and OPPM techniques increased compared with OFM, and OFM became the most cost-effective method of open repair. TEP dominated TAPP, as it was less costly and more effective than the TAPP method of repair. The incremental cost of laparoscopic surgery compared with OFM was between £5000 and £12,000 per QALY at 5 years and between £2000 and £5000 per QALY at 25 years for TEP and TAPP, respectively. When the cost effectiveness of laparoscopic surgery was compared with OPM repair, laparoscopic surgery was not cost effective (with an ICER of £46,000–£606,000), and TEP was only cost effective (£20,000 per QALY) if the benefits extended for 25 years. Sensitivity analysis for differences in the costs, utility and relative effectiveness of different methods of open and laparoscopic repair was undertaken to evaluate the effect of uncertainty in these areas; most of these had little effect on the cost effectiveness of laparoscopic surgery. However, the cost effectiveness of laparoscopic repair was shown to be highly dependent on the cost of the open repair comparator. Sensitivity analysis that assumed that laparoscopic surgery did not improve the level of persistent numbness compared with OFM, increased the ICER of TEP from £2000 per QALY at baseline to £4000 per QALY at 25 years. Sensitivity analysis that assumed that laparoscopic surgery did not improve the level of persistent pain, increased the ICER of TEP from £2000 per QALY at baseline to £8000 per QALY at 25 years. Assumptions that laparoscopic surgery did not confer any benefits of reduced persistent pain or numbness increased the ICER of TEP to approximately £100,000 per QALY at 25 years. The use of reusable (approximately £170 per procedure) or disposable (approximately £790 per procedure) equipment in laparoscopic surgery had a huge impact on the cost effectiveness of surgery. Laparoscopic surgery using disposable equipment increased the ICER of TEP from £2000 per QALY at baseline to £14,000 per QALY at 25 years. In a separate analysis, the Assessment Group modelled the effect of repairing occult bilateral hernias on the cost effectiveness of laparoscopic surgery. This led to an increase in the cost of laparoscopic surgery compared with OFM, and a reduction in the probability of recurrence (as it has already been repaired) in the first year, increasing the ICER of TEP from £5000 per QALY at baseline to up to £10,000 per QALY at 5 years, depending on the prevalence and rate of progression of occult hernia. A supplementary analysis was undertaken by the Assessment Team in order to evaluate the effect of inclusion of new data from the study published after completion of the original report (4.1.12). This also incorporated a number of sensitivity analyses evaluating the cost effectiveness of laparoscopic surgery, using data from the most recent trial, which led to more conservative estimates of the reduction in persistent pain and an increased RR of hernia recurrence with laparoscopic repair. Thus when the baseline recurrence rate for all laparoscopic surgery was increased from a cumulative rate of approximately 3% in the original base-case analysis to 10% at 2 years (based on the recent paper), the ICER of TEP compared with OFM was £6500 per QALY at a 25-year time horizon. When the RR of persistent pain was reduced from 0.77 in the original model, to 0.69 based on the results of the recent study, the ICER of TEP compared with OFM repair was £4000 per QALY at a 25-year time horizon. With these scenarios TAPP and TEP were associated with costs and effects that were increasingly similar. # Consideration of the evidence The Committee reviewed the data available on the clinical and cost effectiveness of laparoscopic surgery for inguinal hernia repair, having considered evidence on the nature of the condition and the value placed on the benefits of laparoscopic surgery for inguinal hernia repair by people with the condition, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources. The Committee heard evidence from experts that the incision resulting from open hernia repair may cause damage to the tissues and nerves, leaving some people with long-term pain and numbness. Experts further advised that all the open methods of repair (OFM, OPPM and OPM) would be expected to have similar incidences of persistent pain and numbness. The Committee considered carefully the evidence from the RCTs on the potentially higher incidences of visceral and vascular injuries associated with laparoscopic hernia repair compared with open procedures. In addition, the evidence from the RCTs suggests that the incidences of these important adverse events may be different between the two laparoscopic procedures. Experts advised that this may have been a result of the relative lack of experience of surgeons in some of these early studies, and advised that there is currently no significant difference in the rate of adverse events between the two laparoscopic procedures when performed by experienced surgeons. The Committee considered carefully the recent study (4.1.12), which reported a significantly higher incidence of serious complications with laparoscopic repair compared with open repair (although this was not reported separately for TAPP and TEP repairs). Many of the adverse events may have been related to the effects of the general anaesthetic used in the patients undergoing laparoscopic repair coupled with the relatively poorer general health of patients recruited into this study (that is, two-thirds in ASA groups II and III) compared with patients included in the original systematic review. However, the Committee were persuaded that the patients in this trial were probably representative of the unselected patients undergoing operations for inguinal hernia in the NHS and therefore considered that inclusion of the data from this study in the overall analysis was appropriate. The Committee appreciated that differences in the outcomes and adverse events of laparoscopic surgery, which may occur in practice and are apparent in the recent study (4.1.12), could result from differences in surgical experience. The Committee were persuaded that ongoing evaluation and review of the results of laparoscopic hernia repair was important and that this should be established at a national level to ensure that potentially serious events are identified and recorded in individual centres. The Committee considered the uncertainty over the recurrence rate associated with laparoscopic surgery, which was statistically significantly higher than that associated with open repair when data from the recent study were incorporated. The Committee concluded that the risk of recurrence which was relatively low with both procedures, and that the increased risk of recurrence with laparoscopic surgery may be acceptable for some patients when the benefits (reduced pain and numbness, and earlier return to normal activities) are taken into consideration. In summary, the Committee considered that laparoscopic repair of inguinal hernia was likely to result in considerably less postoperative pain and numbness than open repair. However, there was uncertainty over the rates of recurrence and of serious complications associated with laparoscopic surgery for primary repairs, which may be higher than those associated with the open procedure. On balance, the Committee concluded that laparoscopic surgery would be the preferred technique for the repair of recurrent hernias (as scar tissue from previous open repairs may be avoided) and bilateral hernias (repaired during the same operation and should also be an option for primary repair of unilateral hernias because of the reduced incidence of long-term pain and numbness and the potential for earlier return to normal activities. The Committee considered that current evidence did not suggest which of the two available laparoscopic methods should be preferred for routine surgery, and noted the importance of the individual surgeon's experience in each method as a factor in determining the best choice. The Committee was advised that the TAPP approach enabled the surgeon to both view, and if required, effect a repair of an occult hernia on the contralateral side during a primary repair procedure. The TEP approach also allowed an occult hernia on the contralateral side to be seen, but required more dissection to facilitate repair. The Committee was aware that laparoscopic (TAPP and TEP) methods of repair are technically more demanding than open repair, and that the clinical and the cost effectiveness of laparoscopic hernia repair are closely linked to the experience of the surgeon in the technique. The Committee heard evidence from experts that whilst surgeons are being trained in laparoscopic surgery, there is likely to be an increase in the duration of the operation, but were persuaded that this would not affect the overall longer-term cost effectiveness of the procedure. The Committee was persuaded of the importance of ensuring appropriate standards of training for laparoscopic hernia repair. They considered that, in light of the relatively small number of surgeons currently proficient in laparoscopic techniques (as compared with those undertaking open repair procedures), further training of surgeons in laparoscopic methods of repair will be required before this procedure can be more widely adopted. The Committee considered it important that individuals be advised of the potential risk of complications associated with laparoscopic surgery. Laparoscopic surgery would not be appropriate for all, particularly those people unable to undergo or at higher risk from general anaesthesia, or in situations where the size or location of the hernia defect does not lend itself to laparoscopic surgery. Experts advised that individual surgeons tend to have a favoured method of open or laparoscopic repair. The Committee concluded that individuals should be given impartial advice as to the relative risks and benefits of laparoscopic repair compared with open repair during discussions with the surgeon at the time of referral, in order to facilitate an informed choice. The Committee reviewed the data on the cost effectiveness of laparoscopic repair compared with the different methods of open repair, and considered the OFM technique to be the most clinically relevant comparator because it is the most common method of open repair and because of the absence of long-term data on the costs and outcomes of newer techniques (OPPM and OPM). The Committee considered that, taking all data reviewed into account, laparoscopic surgery (TAPP and TEP) is a cost-effective alternative to OFM repair. However, they noted that the choice of disposable or reusable equipment for use in laparoscopic hernia repairs had a significant effect on the ICER of the procedure. The Committee were therefore persuaded that, wherever possible, the use of reusable equipment was to be preferred.# Recommendations for further research The Institute recommends that further trials be undertaken to evaluate the utility of individuals undergoing laparoscopic surgery at 1 year and longer follow-up (where possible, up to 25 years) to provide long-term data on the cost effectiveness of this technique. The issue of chronic pain and numbness after inguinal hernia repair should be addressed prospectively in future studies, using standard definitions to allow for assessment of the degree of pain. It is recommended that a registry be set up to monitor the incidence of serious adverse events (specifically the rates of visceral and vascular injury) associated with laparoscopic hernia repair and recurrence rates.# Implications for the NHS Approximately 70,000 surgical inguinal hernia repairs are performed in England each year, at a cost to the NHS of £56 million a year. In the year 2001/02, 95.9% of mesh repairs were performed by open surgery, and 4.1% of repairs were performed by laparoscopic surgery. The anticipated costs of adopting laparoscopic surgery are based on the degree of diffusion of this technique. However, experts advised that, for the foreseeable future, it is unlikely that the uptake of laparoscopic surgery would exceed 40% of all surgical hernia repairs. If the annual percentage of laparoscopic repairs increased to 20%, the additional cost to the NHS in England would be approximately £1 million (based on the number and cost of hernia repairs in 2001/02 of £1078 for laparoscopic and £987 for open mesh repairs). The cost effectiveness of laparoscopic surgery for inguinal hernia repair is influenced by: the number of laparoscopic procedures performed per annum and the experience of the operating surgeon the use of disposable or reusable laparoscopic equipment the rates of hernia recurrence, serious complications and persistent pain (and its severity). The duration of surgery is directly linked to the experience of the surgeon: the duration of laparoscopic surgery decreases as the operating surgeon's experience increases, and this should reduce the costs attributable to theatre time. Operating costs for open and laparoscopic repairs done by experienced surgeons are likely to be similar. Hospital policy as to the use of reusable or disposable consumables will also have a significant impact on the cost of laparoscopic surgery. Reusable equipment for laparoscopic surgery costs about £170 per procedure compared with disposable equipment, which costs about £790 per procedure. Regional variations in the implementation costs of this guidance are likely, depending on the degree to which laparoscopic surgery is taken up locally, and on variations in hospital policy towards, for example, the use of reusable or disposable equipment.# Related guidance The Institute issued the original guidance on the use of laparoscopic repair of inguinal hernia in January 2001. National Institute for Clinical Excellence (2001) Guidance on the use of laparoscopic surgery for inguinal hernia. NICE Technology Appraisal Guidance No. 18. London: National Institute for Clinical Excellence.# Review of guidance The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review. The guidance on this technology will be reviewed in September 2007. Andrew DillonChief ExecutiveSeptember 2004# Appendix C. Detail on criteria for audit of the use of laparoscopic surgery for inguinal hernia repair # Possible objectives for an audit An audit could be carried out on the appropriateness of the use of laparoscopic surgery for inguinal hernia to ensure the following. Laparoscopic surgery is considered as one of the treatment options for the repair of inguinal hernia. Individuals are fully informed of the risks and benefits of alternative procedures. Surgeons carry out laparoscopic surgery for the repair of inguinal hernia only after receiving appropriate training and experience. # Possible patients to be included in the audit An audit could be carried out on all people referred for repair of inguinal hernia in a reasonable time period for audit, for example, 6 months or 1 year. # Measures that could be used as a basis for an audit The measures that could be used in an audit of laparoscopic surgery for inguinal hernia are as follows. Criterion Standard Exception Definition of terms . Laparoscopic surgery is considered as one of the treatment options for the repair of inguinal hernia % of the people referred for repair of inguinal hernia None Surgeons will need to agree locally on how consideration of laparoscopic surgery as a treatment option is recorded for audit purposes. In choosing between open and laparoscopic surgery, the following are considered: (a) the individual's suitability for general anaesthesia; (b) the nature of the presenting hernia; (c) the suitability of the particular hernia for laparoscopic or open approach; (d) the experience of the surgeon in open and laparoscopic procedures. 'Laparoscopic surgery' means the TEP or the TAPP procedure. 'Nature of the presenting hernia' means primary repair, recurrent hernia or bilateral hernias. 'Experience of the surgeon' refers to all three techniques, open surgery and the TEP or TAPP laparoscopic procedures. . The individual undergoing repair of inguinal hernia is fully informed of all the risks and benefits associated with open and laparoscopic surgery through the informed consent process % of people referred for repair of inguinal hernia None 'Risks' include immediate serious complications, post-operative pain or numbness and long-term recurrence. 'Laparoscopic surgery' means either the TEP or the TAPP procedure. Clinicians will need to agree locally on how an individual is determined to be 'fully informed' of risks and benefits for audit purposes. . Laparoscopic repair of inguinal hernia is performed only by a surgeon who: a. has received appropriate training and b. regularly carries out the procedure % of people having laparoscopic repair of inguinal hernia None Clinicians will need to agree locally on what constitutes 'appropriate training' and how many procedures are needed in a given time period to count as 'regularly' carrying out the procedure. # Calculation of compliance Compliance (%) with each measure described in the table above is calculated as follows. Number of patients whose care is consistent with the criterion plus number of patients who meet any exception listed x 100 Number of patients to whom the measure applies Clinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.# Changes after publication March 2014: implementation section updated to clarify that laparoscopic surgery is recommended as a treatment option for repair of inguinal hernia. Additional minor maintenance update also carried out. March 2012: minor maintenance# About this guidance NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales. This guidance replaces 'Laparoscopic surgery for hernia' (NICE Technology Appraisal Guidance 18) issued in January 2001. The Institute reviews each piece of guidance it issues. The review and re-appraisal of the use of laparoscopic surgery for inguinal hernia repair has resulted in changes in the guidance. Specifically there has been: a recommendation that laparoscopic surgery is one of the treatment options for the repair of inguinal hernia a recommendation that patients should be fully informed of all the risks and benefits of open and laparoscopic surgery by either the TAPP or TEP approaches, to enable them to choose between the procedures. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence . All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.	{'Guidance': "This guidance replaces 'Laparoscopic surgery for hernia' (NICE Technology Appraisal Guidance 18) issued in January 2001.\n\nFor details, see 'About this guidance'.\n\nLaparoscopic surgery is recommended as one of the treatment options for the repair of inguinal hernia.\n\nTo enable patients to choose between open and laparoscopic surgery (either by the transabdominal preperitoneal [TAPP] or by the totally extraperitoneal [TEP] procedure), they should be fully informed of all of the risks (for example, immediate serious complications, postoperative pain/numbness and long-term recurrence rates) and benefits associated with each of the three procedures. In particular, the following points should be considered in discussions between the patient and the surgeon:\n\nthe individual's suitability for general anaesthesia\n\nthe nature of the presenting hernia (that is, primary repair, recurrent hernia or bilateral hernia)\n\nthe suitability of the particular hernia for a laparoscopic or an open approach\n\nthe experience of the surgeon in the three techniques.\n\nLaparoscopic surgery for inguinal hernia repair by TAPP or TEP should only be performed by appropriately trained surgeons who regularly carry out the procedure.", 'Clinical need and practice': "An inguinal hernia is a protrusion of a sac of peritoneum (often containing intestine or other abdominal contents) through a weakness in the abdominal wall in the groin. It usually presents as a lump, with or without some discomfort that may limit daily activities and the ability to work. Around 98% of inguinal hernias are found in men because of the vulnerability of the male anatomy to the formation of hernias in this region. Inguinal hernias can occasionally be life-threatening if the bowel within the peritoneal sac strangulates and/or becomes obstructed.\n\nIn England, there were approximately 70,000 surgical repairs of inguinal hernia in 2001/02, affecting 0.14% of the population and utilising over 100,000 NHS bed-days of hospital resources. Of these procedures, 62,969 were for the repair of primary hernias and 4939 for the repair of recurrent hernias.\n\nSurgical repair (herniorraphy) is undertaken in most individuals presenting with inguinal hernia in order to close the defect, alleviate symptoms of discomfort, prevent serious complications (that is, obstruction or strangulation of the bowel) and reduce the risk of recurrence.\n\nMost hernia repairs are undertaken as elective procedures. However, 4.8% of primary repairs and 8.6% of recurrent hernias present as an emergency with a complication. Some individuals present with bilateral hernias, which may be repaired during the same operation or at a later date, and up to 30% of people with a primary unilateral hernia subsequently develop a hernia on the opposite side.\n\nTraditional methods of open repair (for example, the Bassini method), which repair the hernia defect by suturing, have not changed significantly since their introduction in the late 19th century. Recently, the availability of prosthetic meshes has led to an increase in the number of 'tension-free' methods of reinforcing the inguinal region. Open mesh methods of repair are classified as open flat mesh (OFM; for example, the Lichtenstein method), open preperitoneal mesh (OPPM; for example, the Stoppa and Nyhus methods) and open plug and mesh repair (OPM; for example, the Rutkow method). Open methods of hernia repair are associated with postoperative pain and numbness because of the large inguinal incision. OFM repairs are thought to be the principal surgical method of hernia repair in the UK.", 'The technology': 'Laparoscopic surgery is a minimal-access technique that allows the hernia repair to be undertaken without the need to open the abdominal wall. Small incisions are made for the laparoscope and operating instruments, and synthetic mesh is usually used to close the hernia and prevent recurrence. There are two main approaches for the laparoscopic repair of inguinal hernias.\n\nTransabdominal preperitoneal (TAPP) repair involves access to the hernia through the peritoneal cavity. Mesh is inserted through the peritoneum and placed over all potential hernia sites in the inguinal region. The peritoneum is then closed above the mesh.\n\nTotally extraperitoneal (TEP) repair is the newer laparoscopic technique, in which the hernia site is accessed via the preperitoneal plane without entering the peritoneal cavity. TEP repair is considered to be technically more difficult than the TAPP technique, but it may reduce the risk of damage to intra-abdominal organs.\n\nThe surgical approach to inguinal hernia repair is the main focus of this appraisal; other issues, such as comparisons between TAPP and TEP and the use of laparoscopic surgery in special subgroups (for example, bilateral or recurrent hernia), are subsidiary considerations.\n\nThe potential benefits of using a laparoscopic approach include reduced postoperative pain, earlier return to normal activities and a reduction in long-term pain and numbness. The repair of bilateral hernias (including occult hernias detected during contralateral inspection at the time of a unilateral repair) may be undertaken during the same operation.\n\nLaparoscopic surgery is associated with additional costs, for the endoscopy system (video unit, monitor, endoscope and CO2 insufflator) and instruments (staplers, diathermy scissors or ports), although these may be reusable. The cost of laparoscopic surgery is highly dependent on whether disposable or reusable equipment is used.', 'Evidence and interpretation': "The Appraisal Committee (Appendix A) considered evidence from a number of sources (Appendix B).\n\n# Clinical effectiveness\n\nOutcomes of interest, against which the effectiveness of laparoscopic and open surgery were assessed, were primary outcomes of recurrence and persistent pain, and secondary outcomes of the rate of complications and persistent numbness, the duration of the operation, length of hospital stay, time to return to normal activities and quality of life.\n\nA systematic review of the literature identified 37 randomised controlled trials (RCTs) that compared laparoscopic with open mesh repair of inguinal hernias in a total of 5560 participants. The effectiveness of laparoscopic surgery compared with different methods of open surgery (OFM, OPPM and OPM) was presented separately for the TAPP and TEP laparoscopic methods of repair. The best available data (individual patient data, or aggregate data from studies) were used to generate a meta-analysis of the effectiveness of TAPP and TEP procedures for different outcomes of effectiveness.\n\nLaparoscopic surgery was associated with a statistically significant increase in operation time compared with open methods of hernia repair. Meta-analysis of 16 RCTs of TAPP repair demonstrated an overall increase of 13.33\xa0minutes (95% CI 12.08 to 14.57) compared with open repair. Meta-analysis of eight RCTs of TEP repair demonstrated an overall increase of 7.89\xa0minutes (95% CI 6.22 to 9.57) compared with open repair.\n\nLaparoscopic surgery was associated with a significantly shorter time to return to usual activities in all of the studies that measured this outcome. Meta-analysis of seven RCTs of TAPP repair reported a hazard ratio (HR) of 0.66 (95% CI 0.58 to 0.75; p\xa0<\xa00.00001), corresponding to a return to normal activities approximately 3\xa0days earlier than after open repair. Meta-analysis of five RCTs of TEP repair reported an HR of 0.49 (95% CI 0.42 to 0.56; p\xa0<\xa00.00001), approximating to a return to usual activities 4\xa0days earlier than after open repair.\n\nBoth TAPP and TEP procedures demonstrated a statistically significant reduction in persistent numbness compared with open repair. Meta-analysis of eight RCTs comparing TAPP and open repair reported a relative risk (RR) of numbness of 0.26 (95% CI 0.17 to 0.40; p\xa0<\xa00.00001) in favour of TAPP repair. Meta-analysis of four RCTs comparing TEP with open repair reported an RR of 0.67 (95% CI 0.53 to 0.86; p\xa0<\xa00.002) in favour of TEP. One trial (n\xa0=\xa0160) that randomised patients to TAPP or OPM repair reported no significant difference (RR 1.00, 95% CI 0.06 to 15.71 for TAPP) between the two techniques. Another trial that randomised 254 patients to TEP or OPM repair reported no significant difference (RR 2.57, 95% CI 0.11 to 62.38) between the two techniques. One RCT of TAPP compared with open repair showed that the reduction in numbness was maintained at 5-year follow-up (3% persistent numbness with TAPP compared with 23% with OFM repair).\n\nOverall, there were fewer cases of persistent pain at 1\xa0year post-operation after laparoscopic repair, compared with open repair, in both TAPP and TEP studies. Meta-analysis of eight RCTs of TAPP repair reported an RR of 0.72 (95% CI 0.58 to 0.88; p\xa0=\xa00.001) in favour of TAPP. Meta-analysis of four RCTs of TEP repair reported an RR of 0.77 (95% CI 0.64 to 0.92; p\xa0=\xa00.004) in favour of TEP repair. One RCT of TAPP compared with open repair showed that the reduction in pain was maintained at 5-year follow-up (2% persistent pain with TAPP compared with 10% with OFM repair).\n\nThe rates of recurrence were similar for laparoscopic and open repair. Meta-analysis of 15 TAPP RCTs reported a total of 26 recurrences out of 1052 TAPP procedures (2.5%) compared with 22 recurrences out of 1062 open repair procedures (2.1%; RR 1.18, 95% CI 0.69 to 2.02). Thirteen RCTs of TEP repair reported a total of 23 recurrences out of 1007 TEP repairs (2.3%), compared with 13 recurrences out of 1002 open repair procedures (1.3%; RR 1.61, 95% CI 0.87 to 2.98).\n\nA number of studies reported the incidence of adverse events (complications such as haematoma, seroma, wound-related infection, mesh infection, vascular or visceral injuries and port-site hernia). Laparoscopic repair (both TAPP and TEP) was associated with fewer cases of wound-related infection and haematoma. However, TAPP repair was associated with a higher incidence of vascular and visceral injuries compared with open repair (0.13% vascular injuries with TAPP compared with 0% with TEP and open repair; 0.79% visceral injuries with TAPP compared with 0.16% with TEP and 0.14% with open repair).\n\nOne RCT randomised 52 patients with unilateral inguinal hernia to TAPP (n=28) or TEP (n=24) repair. There were no statistically significant differences between the procedures in terms of the duration of operation, intra-operative complications, incidence of haematoma, recurrence at 3-month follow-up, or time to return to usual activities.\n\nThere were no direct comparisons of TAPP and TEP methods of laparoscopic repair in patients with bilateral or recurrent hernia. Trials that evaluated the effectiveness of laparoscopic surgery compared with various forms of open surgery (OFM, OPPM and OPM) in the repair of recurrent inguinal hernias (six trials of TAPP and five trials of TEP) and bilateral inguinal hernias (six trials of TAPP and six trials of TEP) were consistent with the overall results for primary surgery of unilateral inguinal hernias.\n\nThe Assessment Group evaluated the effect of surgeons' experience on the duration of operation for laparoscopic repair (the 'learning effect'). Inexperienced surgeons (up to 20\xa0procedures) were estimated to perform TAPP procedures in 70\xa0minutes and TEP procedures in 95\xa0minutes, compared with experienced surgeons, who were estimated to perform TAPP procedures in 40\xa0minutes and TEP procedures in 55\xa0minutes.\n\nA recent study, published after the Assessment Group's initial review, randomised 2164 patients to laparoscopic surgery (10% TAPP, 90% TEP) or to OFM repair. Many of the results of this study were broadly consistent with the findings of the systematic review and did not affect the pooled results when they were incorporated into meta-analysis. This study reported a statistically significant increase in the recurrence rate with laparoscopic surgery (10.1% for TAPP and TEP combined compared with 4.9% after open repair at 2-year follow up, odds ratio [OR] 2.2, 95% CI 1.5 to 3.2). When the recurrence rates from the recent study were incorporated into meta-analysis of TEP compared with OFM repair, the RR of recurrence associated with laparoscopic surgery was increased from 1.61 (95% CI 0.57 to 4.60), in the original report, to 2.0 (95% CI 1.43 to 2.81). The incidence of serious complications was also significantly higher with laparoscopic repair (1.1%; TAPP and TEP combined) compared with open repair (0.1%; OR 11.2, 95% CI 1.3 to 1.7), although this had little effect on the results when incorporated into the meta-analysis. This study also reported a reduction in persistent pain after laparoscopic compared with open repairs (9.8% after laparoscopic surgery compared with 14.3% after open repair).\n\n# Cost effectiveness\n\nThe literature review identified seven economic evaluations of laparoscopic surgery for inguinal hernia repair – three based on economic models and four based on primary studies. Only two studies (submitted by Ethicon Endo-Surgery and BARD Ltd) were relevant to the UK setting.\n\nEthicon Endo-Surgery provided a re-analysis of data from the MRC Laparoscopic Groin Hernia Trial, taking into consideration the repair of occult bilateral hernias. This model was based on the assumption that bilateral repairs in 30% of people with occult hernias would prevent the need for subsequent operation, and reduced the incremental cost effectiveness ratio (ICER) for laparoscopic surgery from £55,549 per quality-adjusted life year (QALY), as reported in the MRC Laparoscopic Groin Hernia Trial, to £15,000 per QALY. However, the model did not take into account the possibility that some people with occult hernias would not develop a clinically significant hernia.\n\nThe BARD submission compared the cost effectiveness of the Perfix plug (used in OPM repairs) with that of laparoscopic surgery on the basis of data presented in the previous guidance, issued in 2001 (see Section 8). BARD estimated that open plug and mesh repairs may be cost saving on the basis of assumptions that the additional device cost may be offset by reductions in the recurrence rate (0.5% Perfix plug compared with 2.2% with laparoscopic surgery reported in the previous guidance) and an increase in the number of perfix plug repairs undertaken as less costly day cases (91% perfix plug and 60% laparoscopic repairs undertaken as day cases).\n\nThe Assessment Group developed a Markov model that updates the paper by Vale l, Grant A and McCormack K (unpublished data 2003). The cost and outcome of various laparoscopic (TAPP and TEP) and open (OFM, OPPM and OPM) techniques were assessed in 1-year cycles over 5- and 25-year time horizons. All individuals entered the model at the point of initial hernia repair. In the first year, survivors were assumed to undergo a 3-month period of convalescence and then to return to full health. In subsequent years, individuals could be in a health state of no recurrence (with or without persistent pain or numbness), recurrent hernia proceeding to re-operation, recurrence without re-operation (at risk of emergency surgery for complications), or death (operative and all-cause mortality).\n\nInputs to the economic model on the costs and EQ5D utility estimates for the different health states were based on data from the MRC Laparoscopic Groin Hernia Trial. Theatre costs (£6.40 per minute) and in-hospital costs (£236 per day) were similar for open and laparoscopic procedures. The additional equipment and consumable costs of laparoscopic surgery were £167 per procedure when using predominantly reusable equipment (assuming all reusable devices are used on average 250 times a year for 5\xa0years), or £788 per procedure when predominantly disposable equipment is used. Baseline estimates for operation length, hospital stay, operative mortality, recurrence, re-operation, persistent pain and numbness, time away from usual activities and health state utilities were taken from the best available data identified during this systematic review. Relative differences in the effectiveness of the different methods of open and laparoscopic repair were based on the meta-analysis results for the various outcomes, which were applied to these baseline parameters. Probabilities, costs and utilities were not considered to be fixed but were assigned a probability distribution to reflect uncertainty about their values. The same annual risk of recurrence, pain, numbness and relative effect sizes was used for primary and subsequent procedures. A constant annual risk for persistent pain, numbness and recurrence was assumed when extrapolating from years 6 to 25 of the model.\n\nThe results from the model showed that laparoscopic surgery (using reusable equipment) was associated with an increased cost of between £100 and £400 per procedure. Also, QALY differences between all of the techniques were small. Incremental analysis found the OPM method to be the most cost-effective method of open repair, driven by the duration of operation and hospital stay, which was the shortest with this procedure. However, when the same duration of operation and of hospital stay were assumed for all open procedures, the costs of OPM and OPPM techniques increased compared with OFM, and OFM became the most cost-effective method of open repair. TEP dominated TAPP, as it was less costly and more effective than the TAPP method of repair. The incremental cost of laparoscopic surgery compared with OFM was between £5000 and £12,000 per QALY at 5\xa0years and between £2000 and £5000 per QALY at 25\xa0years for TEP and TAPP, respectively. When the cost effectiveness of laparoscopic surgery was compared with OPM repair, laparoscopic surgery was not cost effective (with an ICER of £46,000–£606,000), and TEP was only cost effective (£20,000 per QALY) if the benefits extended for 25\xa0years.\n\nSensitivity analysis for differences in the costs, utility and relative effectiveness of different methods of open and laparoscopic repair was undertaken to evaluate the effect of uncertainty in these areas; most of these had little effect on the cost effectiveness of laparoscopic surgery. However, the cost effectiveness of laparoscopic repair was shown to be highly dependent on the cost of the open repair comparator.\n\nSensitivity analysis that assumed that laparoscopic surgery did not improve the level of persistent numbness compared with OFM, increased the ICER of TEP from £2000 per QALY at baseline to £4000 per QALY at 25\xa0years. Sensitivity analysis that assumed that laparoscopic surgery did not improve the level of persistent pain, increased the ICER of TEP from £2000 per QALY at baseline to £8000 per QALY at 25\xa0years. Assumptions that laparoscopic surgery did not confer any benefits of reduced persistent pain or numbness increased the ICER of TEP to approximately £100,000 per QALY at 25\xa0years. The use of reusable (approximately £170 per procedure) or disposable (approximately £790 per procedure) equipment in laparoscopic surgery had a huge impact on the cost effectiveness of surgery. Laparoscopic surgery using disposable equipment increased the ICER of TEP from £2000 per QALY at baseline to £14,000 per QALY at 25\xa0years. In a separate analysis, the Assessment Group modelled the effect of repairing occult bilateral hernias on the cost effectiveness of laparoscopic surgery. This led to an increase in the cost of laparoscopic surgery compared with OFM, and a reduction in the probability of recurrence (as it has already been repaired) in the first year, increasing the ICER of TEP from £5000 per QALY at baseline to up to £10,000 per QALY at 5\xa0years, depending on the prevalence and rate of progression of occult hernia.\n\nA supplementary analysis was undertaken by the Assessment Team in order to evaluate the effect of inclusion of new data from the study published after completion of the original report (4.1.12). This also incorporated a number of sensitivity analyses evaluating the cost effectiveness of laparoscopic surgery, using data from the most recent trial, which led to more conservative estimates of the reduction in persistent pain and an increased RR of hernia recurrence with laparoscopic repair. Thus when the baseline recurrence rate for all laparoscopic surgery was increased from a cumulative rate of approximately 3% in the original base-case analysis to 10% at 2 years (based on the recent paper), the ICER of TEP compared with OFM was £6500 per QALY at a 25-year time horizon. When the RR of persistent pain was reduced from 0.77 in the original model, to 0.69 based on the results of the recent study, the ICER of TEP compared with OFM repair was £4000 per QALY at a 25-year time horizon. With these scenarios TAPP and TEP were associated with costs and effects that were increasingly similar.\n\n# Consideration of the evidence\n\nThe Committee reviewed the data available on the clinical and cost effectiveness of laparoscopic surgery for inguinal hernia repair, having considered evidence on the nature of the condition and the value placed on the benefits of laparoscopic surgery for inguinal hernia repair by people with the condition, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources.\n\nThe Committee heard evidence from experts that the incision resulting from open hernia repair may cause damage to the tissues and nerves, leaving some people with long-term pain and numbness. Experts further advised that all the open methods of repair (OFM, OPPM and OPM) would be expected to have similar incidences of persistent pain and numbness.\n\nThe Committee considered carefully the evidence from the RCTs on the potentially higher incidences of visceral and vascular injuries associated with laparoscopic hernia repair compared with open procedures. In addition, the evidence from the RCTs suggests that the incidences of these important adverse events may be different between the two laparoscopic procedures. Experts advised that this may have been a result of the relative lack of experience of surgeons in some of these early studies, and advised that there is currently no significant difference in the rate of adverse events between the two laparoscopic procedures when performed by experienced surgeons. The Committee considered carefully the recent study (4.1.12), which reported a significantly higher incidence of serious complications with laparoscopic repair compared with open repair (although this was not reported separately for TAPP and TEP repairs). Many of the adverse events may have been related to the effects of the general anaesthetic used in the patients undergoing laparoscopic repair coupled with the relatively poorer general health of patients recruited into this study (that is, two-thirds in ASA groups II and III) compared with patients included in the original systematic review. However, the Committee were persuaded that the patients in this trial were probably representative of the unselected patients undergoing operations for inguinal hernia in the NHS and therefore considered that inclusion of the data from this study in the overall analysis was appropriate.\n\nThe Committee appreciated that differences in the outcomes and adverse events of laparoscopic surgery, which may occur in practice and are apparent in the recent study (4.1.12), could result from differences in surgical experience. The Committee were persuaded that ongoing evaluation and review of the results of laparoscopic hernia repair was important and that this should be established at a national level to ensure that potentially serious events are identified and recorded in individual centres.\n\nThe Committee considered the uncertainty over the recurrence rate associated with laparoscopic surgery, which was statistically significantly higher than that associated with open repair when data from the recent study were incorporated. The Committee concluded that the risk of recurrence which was relatively low with both procedures, and that the increased risk of recurrence with laparoscopic surgery may be acceptable for some patients when the benefits (reduced pain and numbness, and earlier return to normal activities) are taken into consideration.\n\nIn summary, the Committee considered that laparoscopic repair of inguinal hernia was likely to result in considerably less postoperative pain and numbness than open repair. However, there was uncertainty over the rates of recurrence and of serious complications associated with laparoscopic surgery for primary repairs, which may be higher than those associated with the open procedure. On balance, the Committee concluded that laparoscopic surgery would be the preferred technique for the repair of recurrent hernias (as scar tissue from previous open repairs may be avoided) and bilateral hernias (repaired during the same operation and should also be an option for primary repair of unilateral hernias because of the reduced incidence of long-term pain and numbness and the potential for earlier return to normal activities.\n\nThe Committee considered that current evidence did not suggest which of the two available laparoscopic methods should be preferred for routine surgery, and noted the importance of the individual surgeon's experience in each method as a factor in determining the best choice. The Committee was advised that the TAPP approach enabled the surgeon to both view, and if required, effect a repair of an occult hernia on the contralateral side during a primary repair procedure. The TEP approach also allowed an occult hernia on the contralateral side to be seen, but required more dissection to facilitate repair.\n\nThe Committee was aware that laparoscopic (TAPP and TEP) methods of repair are technically more demanding than open repair, and that the clinical and the cost effectiveness of laparoscopic hernia repair are closely linked to the experience of the surgeon in the technique. The Committee heard evidence from experts that whilst surgeons are being trained in laparoscopic surgery, there is likely to be an increase in the duration of the operation, but were persuaded that this would not affect the overall longer-term cost effectiveness of the procedure. The Committee was persuaded of the importance of ensuring appropriate standards of training for laparoscopic hernia repair. They considered that, in light of the relatively small number of surgeons currently proficient in laparoscopic techniques (as compared with those undertaking open repair procedures), further training of surgeons in laparoscopic methods of repair will be required before this procedure can be more widely adopted.\n\nThe Committee considered it important that individuals be advised of the potential risk of complications associated with laparoscopic surgery. Laparoscopic surgery would not be appropriate for all, particularly those people unable to undergo or at higher risk from general anaesthesia, or in situations where the size or location of the hernia defect does not lend itself to laparoscopic surgery. Experts advised that individual surgeons tend to have a favoured method of open or laparoscopic repair. The Committee concluded that individuals should be given impartial advice as to the relative risks and benefits of laparoscopic repair compared with open repair during discussions with the surgeon at the time of referral, in order to facilitate an informed choice.\n\nThe Committee reviewed the data on the cost effectiveness of laparoscopic repair compared with the different methods of open repair, and considered the OFM technique to be the most clinically relevant comparator because it is the most common method of open repair and because of the absence of long-term data on the costs and outcomes of newer techniques (OPPM and OPM). The Committee considered that, taking all data reviewed into account, laparoscopic surgery (TAPP and TEP) is a cost-effective alternative to OFM repair. However, they noted that the choice of disposable or reusable equipment for use in laparoscopic hernia repairs had a significant effect on the ICER of the procedure. The Committee were therefore persuaded that, wherever possible, the use of reusable equipment was to be preferred.", 'Recommendations for further research': 'The Institute recommends that further trials be undertaken to evaluate the utility of individuals undergoing laparoscopic surgery at 1\xa0year and longer follow-up (where possible, up to 25\xa0years) to provide long-term data on the cost effectiveness of this technique.\n\nThe issue of chronic pain and numbness after inguinal hernia repair should be addressed prospectively in future studies, using standard definitions to allow for assessment of the degree of pain.\n\nIt is recommended that a registry be set up to monitor the incidence of serious adverse events (specifically the rates of visceral and vascular injury) associated with laparoscopic hernia repair and recurrence rates.', 'Implications for the NHS': "Approximately 70,000 surgical inguinal hernia repairs are performed in England each year, at a cost to the NHS of £56\xa0million a year. In the year 2001/02, 95.9% of mesh repairs were performed by open surgery, and 4.1% of repairs were performed by laparoscopic surgery.\n\nThe anticipated costs of adopting laparoscopic surgery are based on the degree of diffusion of this technique. However, experts advised that, for the foreseeable future, it is unlikely that the uptake of laparoscopic surgery would exceed 40% of all surgical hernia repairs. If the annual percentage of laparoscopic repairs increased to 20%, the additional cost to the NHS in England would be approximately £1\xa0million (based on the number and cost of hernia repairs in 2001/02 of £1078 for laparoscopic and £987 for open mesh repairs).\n\nThe cost effectiveness of laparoscopic surgery for inguinal hernia repair is influenced by:\n\nthe number of laparoscopic procedures performed per annum and the experience of the operating surgeon\n\nthe use of disposable or reusable laparoscopic equipment\n\nthe rates of hernia recurrence, serious complications and persistent pain (and its severity).\n\nThe duration of surgery is directly linked to the experience of the surgeon: the duration of laparoscopic surgery decreases as the operating surgeon's experience increases, and this should reduce the costs attributable to theatre time. Operating costs for open and laparoscopic repairs done by experienced surgeons are likely to be similar.\n\nHospital policy as to the use of reusable or disposable consumables will also have a significant impact on the cost of laparoscopic surgery. Reusable equipment for laparoscopic surgery costs about £170 per procedure compared with disposable equipment, which costs about £790 per procedure.\n\nRegional variations in the implementation costs of this guidance are likely, depending on the degree to which laparoscopic surgery is taken up locally, and on variations in hospital policy towards, for example, the use of reusable or disposable equipment.", 'Related guidance': 'The Institute issued the original guidance on the use of laparoscopic repair of inguinal hernia in January 2001.\n\nNational Institute for Clinical Excellence (2001) Guidance on the use of laparoscopic surgery for inguinal hernia. NICE Technology Appraisal Guidance No. 18. London: National Institute for Clinical Excellence.', 'Review of guidance': 'The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review.\n\nThe guidance on this technology will be reviewed in September 2007.\n\nAndrew DillonChief ExecutiveSeptember 2004', 'Appendix C. Detail on criteria for audit of the use of laparoscopic surgery for inguinal hernia repair': "# Possible objectives for an audit\n\nAn audit could be carried out on the appropriateness of the use of laparoscopic surgery for inguinal hernia to ensure the following.\n\nLaparoscopic surgery is considered as one of the treatment options for the repair of inguinal hernia.\n\nIndividuals are fully informed of the risks and benefits of alternative procedures.\n\nSurgeons carry out laparoscopic surgery for the repair of inguinal hernia only after receiving appropriate training and experience.\n\n# Possible patients to be included in the audit\n\nAn audit could be carried out on all people referred for repair of inguinal hernia in a reasonable time period for audit, for example, 6 months or 1 year.\n\n# Measures that could be used as a basis for an audit\n\nThe measures that could be used in an audit of laparoscopic surgery for inguinal hernia are as follows.\n\nCriterion\n\nStandard\n\nException\n\nDefinition of terms\n\n. Laparoscopic surgery is considered as one of the treatment options for the repair of inguinal hernia\n\n% of the people referred for repair of inguinal hernia\n\nNone\n\nSurgeons will need to agree locally on how consideration of laparoscopic surgery as a treatment option is recorded for audit purposes. In choosing between open and laparoscopic surgery, the following are considered: (a) the individual's suitability for general anaesthesia; (b) the nature of the presenting hernia; (c) the suitability of the particular hernia for laparoscopic or open approach; (d) the experience of the surgeon in open and laparoscopic procedures. 'Laparoscopic surgery' means the TEP or the TAPP procedure. 'Nature of the presenting hernia' means primary repair, recurrent hernia or bilateral hernias. 'Experience of the surgeon' refers to all three techniques, open surgery and the TEP or TAPP laparoscopic procedures.\n\n. The individual undergoing repair of inguinal hernia is fully informed of all the risks and benefits associated with open and laparoscopic surgery through the informed consent process\n\n% of people referred for repair of inguinal hernia\n\nNone\n\n'Risks' include immediate serious complications, post-operative pain or numbness and long-term recurrence. 'Laparoscopic surgery' means either the TEP or the TAPP procedure. Clinicians will need to agree locally on how an individual is determined to be 'fully informed' of risks and benefits for audit purposes.\n\n. Laparoscopic repair of inguinal hernia is performed only by a surgeon who:\n\na. has received appropriate training and\n\nb. regularly carries out the procedure\n\n% of people having laparoscopic repair of inguinal hernia\n\nNone\n\nClinicians will need to agree locally on what constitutes 'appropriate training' and how many procedures are needed in a given time period to count as 'regularly' carrying out the procedure.\n\n# Calculation of compliance\n\nCompliance (%) with each measure described in the table above is calculated as follows.\n\nNumber of patients whose care is consistent with the criterion plus number of patients who meet any exception listed\n\n\n\nx 100\n\nNumber of patients to whom the measure applies\n\nClinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.", 'Changes after publication': 'March 2014: implementation section updated to clarify that laparoscopic surgery is recommended as a treatment option for repair of inguinal hernia. Additional minor maintenance update also carried out.\n\nMarch 2012: minor maintenance', 'About this guidance': "NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales.\n\nThis guidance replaces 'Laparoscopic surgery for hernia' (NICE Technology Appraisal Guidance 18) issued in January 2001.\n\nThe Institute reviews each piece of guidance it issues.\n\nThe review and re-appraisal of the use of laparoscopic surgery for inguinal hernia repair has resulted in changes in the guidance. Specifically there has been:\n\na recommendation that laparoscopic surgery is one of the treatment options for the repair of inguinal hernia\n\na recommendation that patients should be fully informed of all the risks and benefits of open and laparoscopic surgery by either the TAPP or TEP approaches, to enable them to choose between the procedures.\n\nWe have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence [YEAR]. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE."}	https://www.nice.org.uk/guidance/ta83	Evidence-based recommendations on laparoscopic surgery for treating inguinal hernia.
c41f0e0ea513653fabce7038147060613a2ae13e	nice	Interstitial laser therapy for breast cancer	Interstitial laser therapy for breast cancer # Guidance Current evidence on the safety and efficacy of interstitial laser therapy for breast cancer does not appear adequate to support the routine use of this procedure. It is suitable for use only within good-quality research studies approved by a research ethics committee and with explicit patient consent. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Interstitial laser therapy is used to treat small tumours of the breast. Standard treatments include lumpectomy or mastectomy (without preceding laser therapy), and minimally invasive techniques such as radiofrequency ablation or cryotherapy. # Outline of the procedure Interstitial laser therapy is a minimally invasive technique for treating small breast cancers. After locating the tumour using stereotactic techniques or ultrasound, laser energy is delivered into the tumour via a needle probe. This destroys tumour tissue – the aim is to ablate the tumour entirely. # Efficacy The evidence was limited to three small case series and one case report. One study of interstitial laser therapy followed by surgery reported that 98% (43/44) of patients were disease-free at follow-up. However, follow-up ranged from 2 to 26 months, and it was difficult to determine whether the results were attributable to the laser therapy or the surgery. This study also found no histological sign of laser damage in the tumours of 9% (4/44) of patients. For more details, refer to the Sources of evidence section. The Specialist Advisors noted that it was still uncertain whether the procedure could achieve thermal ablation of all malignant tissue. They also noted that there were no data comparing outcomes of the procedure with those of wide excision and radiotherapy. # Safety The following complications were reported in the identified studies: small skin burns 11% (4/35); necrosis of non-tumour tissue caused by incorrectly placed laser 10% (2/20); pain sufficient to stop treatment 7% (3/44); gaseous rupture of tumour 3% (1/35); and haemorrhage 2% (1/44). For more details, refer to the Sources of evidence section. One Specialist Advisor considered that this procedure should not be used outside a clinical trial; another listed the potential adverse effects of the procedure as necrosis, haemorrhage, and liquefaction caused by overheating of the tissue.# Further information The Institute has published technology appraisals on the use of the following drugs for breast cancer: temozolomide, capecitabine, taxanes, trastuzumab and vinorelbine. For further information, visit our website. The Institute issued cancer service guidance called 'Improving Outcomes in Breast Cancer' in August 2002 and is developing a clinical guideline on breast cancer, called 'Breast cancer: diagnosis and treatment'. The expected date of issue of this guideline is September 2007 . Andrew DillonChief ExecutiveSeptember 2004 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedures overview of interstitial laser therapy for breast cancer', March 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication The guidance was considered for reassessment in January 2011 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It has been incorporated into the NICE pathway on early and locally advanced breast cancer, along with other related guidance and products. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of interstitial laser therapy for breast cancer does not appear adequate to support the routine use of this procedure. It is suitable for use only within good-quality research studies approved by a research ethics committee and with explicit patient consent.\n\nPublication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.', 'The procedure': '# Indications\n\nInterstitial laser therapy is used to treat small tumours of the breast. Standard treatments include lumpectomy or mastectomy (without preceding laser therapy), and minimally invasive techniques such as radiofrequency ablation or cryotherapy.\n\n# Outline of the procedure\n\nInterstitial laser therapy is a minimally invasive technique for treating small breast cancers. After locating the tumour using stereotactic techniques or ultrasound, laser energy is delivered into the tumour via a needle probe. This destroys tumour tissue – the aim is to ablate the tumour entirely.\n\n# Efficacy\n\nThe evidence was limited to three small case series and one case report. One study of interstitial laser therapy followed by surgery reported that 98% (43/44) of patients were disease-free at follow-up. However, follow-up ranged from 2 to 26 months, and it was difficult to determine whether the results were attributable to the laser therapy or the surgery. This study also found no histological sign of laser damage in the tumours of 9% (4/44) of patients. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors noted that it was still uncertain whether the procedure could achieve thermal ablation of all malignant tissue. They also noted that there were no data comparing outcomes of the procedure with those of wide excision and radiotherapy.\n\n# Safety\n\nThe following complications were reported in the identified studies: small skin burns 11% (4/35); necrosis of non-tumour tissue caused by incorrectly placed laser 10% (2/20); pain sufficient to stop treatment 7% (3/44); gaseous rupture of tumour 3% (1/35); and haemorrhage 2% (1/44). For more details, refer to the Sources of evidence section.\n\nOne Specialist Advisor considered that this procedure should not be used outside a clinical trial; another listed the potential adverse effects of the procedure as necrosis, haemorrhage, and liquefaction caused by overheating of the tissue.', 'Further information': "The Institute has published technology appraisals on the use of the following drugs for breast cancer: temozolomide, capecitabine, taxanes, trastuzumab and vinorelbine. For further information, visit our website.\n\nThe Institute issued cancer service guidance called 'Improving Outcomes in Breast Cancer' in August 2002 and is developing a clinical guideline on breast cancer, called 'Breast cancer: diagnosis and treatment'. The expected date of issue of this guideline is September 2007 [Now published as 'Breast cancer (early and locally advanced): diagnosis and treatment'].\n\nAndrew DillonChief ExecutiveSeptember 2004\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedures overview of interstitial laser therapy for breast cancer', March 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': 'The guidance was considered for reassessment in January 2011 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt has been incorporated into the NICE pathway on early and locally advanced breast cancer, along with other related guidance and products.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg89
c2a02f2d94b2350898a970fffd7363060a8c80ac	nice	Intralesional photocoagulation of subcutaneous congenital vascular disorders	Intralesional photocoagulation of subcutaneous congenital vascular disorders # Guidance Current evidence on the safety and efficacy of intralesional photocoagulation of subcutaneous congenital vascular disorders does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake intralesional photocoagulation of subcutaneous congenital vascular disorders should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having intralesional photocoagulation of subcutaneous congenital vascular disorders. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute is not undertaking further investigation at present.# The procedure # Indications Intralesional photocoagulation is a laser treatment for people with congenital abnormalities of the blood vessels of the skin (including haemangiomas, port wine stains and arteriovenous malformations). Often these abnormalities require no treatment because they may resolve spontaneously or cause only mild cosmetic problems. Laser treatment is often recommended for lesions near the eyes or orifices, or if lesions bleed, ulcerate or become infected. However, external laser treatment of these vascular abnormalities may not be effective because the laser beam does not penetrate far beneath the skin. # Outline of the procedure Intralesional photocoagulation involves inserting a laser fibre into the lesion to deliver light deep within it. More than one treatment may be needed. # Efficacy The evidence was limited to small case series studies. The largest study, which only included children, reported that after intralesional photocoagulation, 46% (46/100) of patients had a greater than 90% reduction in the size of the lesion, and the other 54% (54/100) had a 50–90% reduction in the size of the lesion. In this study, 76% (76/100) of patients had a subsequent surgical resection and reconstruction. In another study of patients with periorbital haemangiomas, 83% (19/23) of patients had a 50% or greater reduction in the size of the lesion within 8 months. For more details, refer to the Sources of evidence section. The Specialist Advisors noted that use of the procedure in the UK was very limited. # Safety The following complications were reported in the identified studies: ulceration 17% (4/23) to 25% (3/12); continued gradual bleeding requiring surgical control 8% (1/12); scar contracture needing surgical revision 8% (1/12); infection 4% (1/23); residual weakness of branches of the facial nerve 2% (2/100); requirement for transfusion during treatment 2% (2/100); and small burns 2% (2/100). For more details, refer to the Sources of evidence section. The Specialist Advisors listed the main potential adverse events as ulceration, nerve injury, tissue necrosis, scarring, contracture, and arteriovenous fistula formation. # Other comments The commonest outcome measure in the studies was reduction in the size of the lesions. Evidence on other outcome measures, such as function or the need for further treatment, was very limited. The procedure may sometimes be used as an adjunct to surgery; this can make interpretation of outcomes more difficult. There is particular uncertainty in the literature about the severity and consequences of ulceration and scarring caused by the procedure. Facial nerve damage is an important potential complication. Andrew DillonChief ExecutiveSeptember 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedures overview of intralesional photocoagulation of subcutaneous congenital vascular disorders', May 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication The guidance was considered for reassessment in March 2008 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of intralesional photocoagulation of subcutaneous congenital vascular disorders does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake intralesional photocoagulation of subcutaneous congenital vascular disorders should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having intralesional photocoagulation of subcutaneous congenital vascular disorders.\n\nPublication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute is not undertaking further investigation at present.", 'The procedure': '# Indications\n\nIntralesional photocoagulation is a laser treatment for people with congenital abnormalities of the blood vessels of the skin (including haemangiomas, port wine stains and arteriovenous malformations). Often these abnormalities require no treatment because they may resolve spontaneously or cause only mild cosmetic problems.\n\nLaser treatment is often recommended for lesions near the eyes or orifices, or if lesions bleed, ulcerate or become infected. However, external laser treatment of these vascular abnormalities may not be effective because the laser beam does not penetrate far beneath the skin.\n\n# Outline of the procedure\n\nIntralesional photocoagulation involves inserting a laser fibre into the lesion to deliver light deep within it. More than one treatment may be needed.\n\n# Efficacy\n\nThe evidence was limited to small case series studies. The largest study, which only included children, reported that after intralesional photocoagulation, 46% (46/100) of patients had a greater than 90% reduction in the size of the lesion, and the other 54% (54/100) had a 50–90% reduction in the size of the lesion. In this study, 76% (76/100) of patients had a subsequent surgical resection and reconstruction. In another study of patients with periorbital haemangiomas, 83% (19/23) of patients had a 50% or greater reduction in the size of the lesion within 8 months. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors noted that use of the procedure in the UK was very limited.\n\n# Safety\n\nThe following complications were reported in the identified studies: ulceration 17% (4/23) to 25% (3/12); continued gradual bleeding requiring surgical control 8% (1/12); scar contracture needing surgical revision 8% (1/12); infection 4% (1/23); residual weakness of branches of the facial nerve 2% (2/100); requirement for transfusion during treatment 2% (2/100); and small burns 2% (2/100). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors listed the main potential adverse events as ulceration, nerve injury, tissue necrosis, scarring, contracture, and arteriovenous fistula formation.\n\n# Other comments\n\nThe commonest outcome measure in the studies was reduction in the size of the lesions. Evidence on other outcome measures, such as function or the need for further treatment, was very limited.\n\nThe procedure may sometimes be used as an adjunct to surgery; this can make interpretation of outcomes more difficult.\n\nThere is particular uncertainty in the literature about the severity and consequences of ulceration and scarring caused by the procedure.\n\nFacial nerve damage is an important potential complication.\n\nAndrew DillonChief ExecutiveSeptember 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedures overview of intralesional photocoagulation of subcutaneous congenital vascular disorders', May 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': 'The guidance was considered for reassessment in March 2008 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg90
ec0313e8c2fd58a4f07642b42ef42b277efe2ae5	nice	Selective peripheral denervation for cervical dystonia	Selective peripheral denervation for cervical dystonia # Guidance Current evidence on the safety and efficacy of selective peripheral denervation for cervical dystonia appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. The procedure should be performed by a multidisciplinary team in a specialist neurosurgical unit. Patient selection for this procedure is important. Patients should be offered the procedure only when their disease has become refractory to best medical treatment.# The procedure # Indications Cervical dystonia is a condition in which the muscles of the neck contract painfully and cause twisting of the head. The head may be pulled backwards (retrocollis), forwards (anterocollis) or to the side (torticollis), depending on which muscle groups are affected. This muscle spasm may occur intermittently or continuously. The cause of cervical dystonia is not known. In children, it is sometimes associated with congenital abnormalities of the shape of the head or of the spine, but it may occur at any age. Cervical dystonia may persist for several years, or sometimes for life. Some patients recover spontaneously. Standard treatment for cervical dystonia includes physiotherapy, drugs to reduce spasm, injections of botulinum toxin, and brain surgery. Selective peripheral denervation may be an alternative, especially for people who have not responded to other treatments. # Outline of the procedure Selective peripheral denervation is a surgical procedure that varies according to the muscle groups affected. It is performed under general anaesthetic and involves cutting, through a skin incision, the nerves that supply the affected muscles. Sometimes the muscles themselves may be divided. # Efficacy The evidence was limited to one systematic review and several case series studies. The review found no controlled studies and no reliable evidence to compare the procedure with other treatments. Two of the larger case series studies found 'very good to excellent' results in 88% (228/260 and 182/207) of patients at follow-up. However, the time to follow-up and how these outcomes were assessed were not specified in either of these two studies. For more details, refer to the Sources of evidence section. One Specialist Advisor noted that careful patient selection should improve the efficacy of the procedure. # Safety The largest case series study identified reported the following complications: occasional tic-like pain (1%, 3/260); tonsillar abscess (0.4%, 1/260); transient swelling of the neck in a few patients (number not specified); and pins and needles or sensation of tightness or fullness in a few patients (number not specified). For more details, refer to the Sources of evidence section. The Specialist Advisors listed potential adverse events as difficulty in swallowing, as well as the usual potential complications of surgery, such as infection and haemorrhage. # Other comments It was noted from the evidence that almost all patients suffered some sensory loss. There was good long-term follow-up. Andrew DillonChief ExecutiveAugust 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of selective peripheral denervation for cervical dystonia', December 2002. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of selective peripheral denervation for cervical dystonia appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe procedure should be performed by a multidisciplinary team in a specialist neurosurgical unit.\n\nPatient selection for this procedure is important. Patients should be offered the procedure only when their disease has become refractory to best medical treatment.', 'The procedure': "# Indications\n\nCervical dystonia is a condition in which the muscles of the neck contract painfully and cause twisting of the head. The head may be pulled backwards (retrocollis), forwards (anterocollis) or to the side (torticollis), depending on which muscle groups are affected. This muscle spasm may occur intermittently or continuously. The cause of cervical dystonia is not known. In children, it is sometimes associated with congenital abnormalities of the shape of the head or of the spine, but it may occur at any age. Cervical dystonia may persist for several years, or sometimes for life. Some patients recover spontaneously.\n\nStandard treatment for cervical dystonia includes physiotherapy, drugs to reduce spasm, injections of botulinum toxin, and brain surgery. Selective peripheral denervation may be an alternative, especially for people who have not responded to other treatments.\n\n# Outline of the procedure\n\nSelective peripheral denervation is a surgical procedure that varies according to the muscle groups affected. It is performed under general anaesthetic and involves cutting, through a skin incision, the nerves that supply the affected muscles. Sometimes the muscles themselves may be divided.\n\n# Efficacy\n\nThe evidence was limited to one systematic review and several case series studies. The review found no controlled studies and no reliable evidence to compare the procedure with other treatments. Two of the larger case series studies found 'very good to excellent' results in 88% (228/260 and 182/207) of patients at follow-up. However, the time to follow-up and how these outcomes were assessed were not specified in either of these two studies. For more details, refer to the Sources of evidence section.\n\nOne Specialist Advisor noted that careful patient selection should improve the efficacy of the procedure.\n\n# Safety\n\nThe largest case series study identified reported the following complications: occasional tic-like pain (1%, 3/260); tonsillar abscess (0.4%, 1/260); transient swelling of the neck in a few patients (number not specified); and pins and needles or sensation of tightness or fullness in a few patients (number not specified). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors listed potential adverse events as difficulty in swallowing, as well as the usual potential complications of surgery, such as infection and haemorrhage.\n\n# Other comments\n\nIt was noted from the evidence that almost all patients suffered some sensory loss.\n\nThere was good long-term follow-up.\n\nAndrew DillonChief ExecutiveAugust 2004", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of selective peripheral denervation for cervical dystonia', December 2002.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg80
a4864d5b5d6b7876b5b8bca802608cefa673e8f2	nice	Supraorbital minicraniotomy for intracranial aneurysm	Supraorbital minicraniotomy for intracranial aneurysm # Guidance Current evidence on the safety and efficacy of supraorbital minicraniotomy for intracranial aneurysm appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.# The procedure # Indications Cerebral aneurysms are small balloon-like dilated portions of blood vessels that may occasionally rupture, causing haemorrhage, stroke or death. Therapy is designed to support recovery from the initial bleed, together with specific treatment to prevent re-bleeding. The majority of cerebral aneurysms arise from the major blood vessels in the centre of the head as they cross the space between the skull and the brain (the subarachnoid space). The standard surgical approach to this area is through an incision in the scalp, just in front of the ear, and an opening in the underlying bone on the side of the head. The abnormal vessels are approached side-on in the subarachnoid space beneath the brain. The surgical treatment of cerebral aneurysms involves placing a permanent clip across the neck of the aneurysm (effectively closing the neck of the balloon) to separate it from the normal vessel while preserving blood flow to the brain. If clipping is not possible, the aneurysm may be reinforced by wrapping it with synthetic material to reduce the risk of rupture. # Outline of the procedure Supraorbital minicraniotomy is an alternative approach through a smaller incision made above the eyebrow and through the underlying skull. This allows a front-on approach to the abnormal vessels. The aneurysm is then clipped or wrapped using conventional microsurgical instruments. # Efficacy No controlled studies were identified. In two studies, all the aneurysms were either successfully clipped or wrapped, but length of follow-up was not reported. In another study, 89% (33/37 patients) showed good recovery on the Glasgow Outcome Scale, but it was not clear how many of the patients were followed up for the entire duration of the study (17 months). This study also reported good cosmetic outcomes following surgery. For more details, refer to the Sources of evidence section. One Specialist Advisor considered it unlikely that the efficacy of treating an aneurysm would be affected by the small exposure used in this procedure when compared with the standard surgical approach. # Safety In the three case series reviewed, rupture of the aneurysm during surgery occurred in 3% (4/139), 2% (2/102) and 3% (1/37) of patients. Other adverse events were: death within 8 days of surgery (4%, 4/102); central nervous system infection (2%, 2/102); impaired cerebrospinal fluid circulation requiring shunting (7%, 7/102); supraorbital nerve damage (11%, 4/37); and wound infection (3%, 1/37). For more details, refer to the Sources of evidence section. The Specialist Advisors had no major safety concerns. # Other comments This procedure involves a different surgical approach for performing an established procedure (craniotomy for intracranial aneurysm) and, although there may be a greater risk of per-operative rupture, this has usually been managed successfully. There is an increasing trend to deal with aneurysms by endoluminal techniques. Andrew DillonChief ExecutiveAugust 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of supraorbital minicraniotomy for intracranial aneurysm', December 2002. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of supraorbital minicraniotomy for intracranial aneurysm appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.', 'The procedure': '# Indications\n\nCerebral aneurysms are small balloon-like dilated portions of blood vessels that may occasionally rupture, causing haemorrhage, stroke or death. Therapy is designed to support recovery from the initial bleed, together with specific treatment to prevent re-bleeding.\n\nThe majority of cerebral aneurysms arise from the major blood vessels in the centre of the head as they cross the space between the skull and the brain (the subarachnoid space). The standard surgical approach to this area is through an incision in the scalp, just in front of the ear, and an opening in the underlying bone on the side of the head. The abnormal vessels are approached side-on in the subarachnoid space beneath the brain. The surgical treatment of cerebral aneurysms involves placing a permanent clip across the neck of the aneurysm (effectively closing the neck of the balloon) to separate it from the normal vessel while preserving blood flow to the brain. If clipping is not possible, the aneurysm may be reinforced by wrapping it with synthetic material to reduce the risk of rupture.\n\n# Outline of the procedure\n\nSupraorbital minicraniotomy is an alternative approach through a smaller incision made above the eyebrow and through the underlying skull. This allows a front-on approach to the abnormal vessels. The aneurysm is then clipped or wrapped using conventional microsurgical instruments.\n\n# Efficacy\n\nNo controlled studies were identified. In two studies, all the aneurysms were either successfully clipped or wrapped, but length of follow-up was not reported. In another study, 89% (33/37 patients) showed good recovery on the Glasgow Outcome Scale, but it was not clear how many of the patients were followed up for the entire duration of the study (17 months). This study also reported good cosmetic outcomes following surgery. For more details, refer to the Sources of evidence section.\n\nOne Specialist Advisor considered it unlikely that the efficacy of treating an aneurysm would be affected by the small exposure used in this procedure when compared with the standard surgical approach.\n\n# Safety\n\nIn the three case series reviewed, rupture of the aneurysm during surgery occurred in 3% (4/139), 2% (2/102) and 3% (1/37) of patients. Other adverse events were: death within 8 days of surgery (4%, 4/102); central nervous system infection (2%, 2/102); impaired cerebrospinal fluid circulation requiring shunting (7%, 7/102); supraorbital nerve damage (11%, 4/37); and wound infection (3%, 1/37). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors had no major safety concerns.\n\n# Other comments\n\nThis procedure involves a different surgical approach for performing an established procedure (craniotomy for intracranial aneurysm) and, although there may be a greater risk of per-operative rupture, this has usually been managed successfully.\n\nThere is an increasing trend to deal with aneurysms by endoluminal techniques.\n\nAndrew DillonChief ExecutiveAugust 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of supraorbital minicraniotomy for intracranial aneurysm', December 2002.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg84
cba5caa4cc64ea127308abb98afc4076995ccc18	nice	Endovascular atrial septostomy	Endovascular atrial septostomy # Guidance Current evidence on the safety and efficacy of endovascular atrial septostomy appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Endovascular atrial septostomy should be undertaken only by specialist paediatric cardiology teams. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database.# The procedure # Indications This procedure is undertaken to relieve the symptoms of cyanotic congenital heart disease by improving the flow of oxygenated blood to the systemic circulation. There are several types of cyanotic congenital heart disease for which this procedure is indicated. Among these is transposition of the great arteries, an uncommon congenital cardiac anomaly in which the aorta arises from the right ventricle and the pulmonary trunk arises from the left ventricle. This results in two separate circuits of blood flow, in which highly oxygenated blood recycles through the lungs, while oxygen-depleted blood recycles around the body. As a result, the baby develops a blue colour (cyanosis) shortly after birth. The baby can survive for a few days because the foramen ovale (a small hole in the fetal interatrial septum) allows some oxygenated blood to mix with the blood that is being recirculated around the body. However, the foramen ovale normally closes days after birth, and the only babies then likely to survive are those with a congenital ventricular septal defect. There is no reliable alternative to septostomy procedures in babies. # Outline of the procedure Endovascular atrial septostomy is a procedure that is used to enlarge the foramen ovale. A catheter is passed through a large vein, usually in the groin, into the right atrium and through the foramen ovale to the left atrium. In simple balloon septostomy, a balloon at the end of the catheter is inflated and pulled back into the right atrium, so enlarging the foramen ovale. When this procedure is unsuccessful or contraindicated, static balloon atrial septostomy is used to enlarge an inter-atrial communication. The septum is cut using a catheter with a blade at its end. The balloon is then used to enlarge the opening in the septum. The procedure aims to prolong survival until definitive surgery can be performed. # Efficacy No controlled studies were identified and many of the studies found were published more than 15 years ago. One of the studies reported an 'immediate haemodynamic effect' in 95% (508/535) of patients. Another reported a mean increase in arterial oxygen saturation of 21%; two other studies reported increases of 21% and 16% in median systemic arterial oxygen saturation. For more details, refer to the Sources of evidence section. The Specialist Advisors regarded this procedure as established practice. They also noted that the septostomy may close spontaneously, necessitating surgical septectomy. # Safety Among the identified studies, mortality from the procedure ranged from 2% (2/104, 3/149) to 3% (3/108). One study reported a minor complication rate of 10% (26/248) and a lethal complication rate of 1% (3/248). For more details, refer to the Sources of evidence section. The Specialist Advisors considered the main safety concerns to be death, transient arrhythmias and cardiac injuries. # Other comments This procedure has become established as a life-saving measure for severely ill neonates, but clinical trial data are very limited. The majority of the evidence relates to the simple balloon method. The evidence on static balloon atrial septostomy is more limited. Andrew DillonChief ExecutiveAugust 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of endovascular atrial septostomy', March 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication May 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of endovascular atrial septostomy appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nEndovascular atrial septostomy should be undertaken only by specialist paediatric cardiology teams.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database.', 'The procedure': "# Indications\n\nThis procedure is undertaken to relieve the symptoms of cyanotic congenital heart disease by improving the flow of oxygenated blood to the systemic circulation. There are several types of cyanotic congenital heart disease for which this procedure is indicated. Among these is transposition of the great arteries, an uncommon congenital cardiac anomaly in which the aorta arises from the right ventricle and the pulmonary trunk arises from the left ventricle. This results in two separate circuits of blood flow, in which highly oxygenated blood recycles through the lungs, while oxygen-depleted blood recycles around the body. As a result, the baby develops a blue colour (cyanosis) shortly after birth. The baby can survive for a few days because the foramen ovale (a small hole in the fetal interatrial septum) allows some oxygenated blood to mix with the blood that is being recirculated around the body. However, the foramen ovale normally closes days after birth, and the only babies then likely to survive are those with a congenital ventricular septal defect.\n\nThere is no reliable alternative to septostomy procedures in babies.\n\n# Outline of the procedure\n\nEndovascular atrial septostomy is a procedure that is used to enlarge the foramen ovale. A catheter is passed through a large vein, usually in the groin, into the right atrium and through the foramen ovale to the left atrium. In simple balloon septostomy, a balloon at the end of the catheter is inflated and pulled back into the right atrium, so enlarging the foramen ovale. When this procedure is unsuccessful or contraindicated, static balloon atrial septostomy is used to enlarge an inter-atrial communication. The septum is cut using a catheter with a blade at its end. The balloon is then used to enlarge the opening in the septum. The procedure aims to prolong survival until definitive surgery can be performed.\n\n# Efficacy\n\nNo controlled studies were identified and many of the studies found were published more than 15 years ago. One of the studies reported an 'immediate haemodynamic effect' in 95% (508/535) of patients. Another reported a mean increase in arterial oxygen saturation of 21%; two other studies reported increases of 21% and 16% in median systemic arterial oxygen saturation. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors regarded this procedure as established practice. They also noted that the septostomy may close spontaneously, necessitating surgical septectomy.\n\n# Safety\n\nAmong the identified studies, mortality from the procedure ranged from 2% (2/104, 3/149) to 3% (3/108). One study reported a minor complication rate of 10% (26/248) and a lethal complication rate of 1% (3/248). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered the main safety concerns to be death, transient arrhythmias and cardiac injuries.\n\n# Other comments\n\nThis procedure has become established as a life-saving measure for severely ill neonates, but clinical trial data are very limited.\n\nThe majority of the evidence relates to the simple balloon method.\n\nThe evidence on static balloon atrial septostomy is more limited.\n\nAndrew DillonChief ExecutiveAugust 2004", 'Further information ': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of endovascular atrial septostomy', March 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nMay 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg86
79886db84fdcbc476bf8f953fed478bb5046b817	nice	Frequency of application of topical corticosteroids for atopic eczema	Frequency of application of topical corticosteroids for atopic eczema Evidence-based recommendations on using topical corticosteroids for people with atopic eczema. # Guidance This appraisal relates to the frequency of application of topical corticosteroids in the treatment of atopic eczema. It does not include the use of topical agents that combine corticosteroids with other active agents (for example, antimicrobials or salicylic acid). It is recommended that topical corticosteroids for atopic eczema should be prescribed for application only once or twice daily. It is recommended that where more than one alternative topical corticosteroid is considered clinically appropriate within a potency class, the drug with the lowest acquisition cost should be prescribed, taking into account pack size and frequency of application.# Clinical need and practice Atopic eczema (synonymous with atopic dermatitis) is a chronic relapsing skin condition characterised by intense itching, dry skin, redness, inflammation and exudation. It affects mainly the flexor surfaces of the elbows and knees, as well as the face and neck. The term 'atopic' refers to the association with atopy (a state of hypersensitivity to common environmental allergens that may be inherited), and differentiates atopic eczema from other forms of eczema such as irritant, allergic contact, discoid, venous, seborrhoeic and photosensitive eczema, which have different disease patterns and aetiologies. Estimates of prevalence vary but suggest that the condition may affect as many as 15–20% of school-age children and 2–10% of adults. Most people with atopic eczema (more than 80%) experience mild disease; only around 2–4% of people with eczema have a severe form of the disease. Despite the lower prevalence, the presentation of disease in adults is often more severe and chronic in nature. In most people with atopic eczema, the condition begins in early childhood – often in the first year of life – when it can be particularly severe. Findings from the National Child Development Study (NCDS), developed from the birth cohort of 1958, suggested an incidence of around 50 cases per 1000 in the first year of life, falling to 5 new cases per 1000 per year for the rest of childhood. In around 60% of children, the condition clears by the time they reach their teens. However, the tendency towards dry and irritable skin generally persists and later recurrences are common. The aetiology of atopic eczema is complex and not fully understood. Genetic factors are important but environmental factors – such as house dust mites, pollen, tobacco, air pollution and low humidity – may cause its onset and/or exacerbate existing symptoms. More persistent disease has been consistently linked with early disease onset, severe widespread disease in early life, concomitant asthma or hay fever, and a family history of atopic eczema. The condition is exacerbated by soap and detergents, clothes containing wool or certain synthetic fibres, and extremes of temperature. The severity of atopic eczema varies enormously, from an occasional dry, scaly patch to a debilitating disease, where much of the body is covered by excoriated, bleeding and infected lesions. Its course may be continuous for prolonged periods or of a relapsing–remitting nature, characterised by acute flare-ups. Itching skin (pruritus) is a major symptom of atopic eczema. A vicious circle can occur, where itching and scratching damage the skin and increase inflammation, which in turn increases the itch. Damage to the skin from scratching can cause bleeding, secondary infection and thickening of the skin (lichenification). The impact of atopic eczema on quality of life can be considerable, and varies according to disease severity. In addition to the burden imposed by daily treatment, studies have shown not only that the condition affects everyday activities such as work or school and social relationships, but also that people with atopic eczema may also experience anxiety, depression and other psychological problems. Sleep disturbance is common, especially during flare-ups, which in turn can lead to problems with irritability and lack of concentration. Severe atopic eczema in children can also have a significant impact on family life, with parents/carers having to cope with the demands associated with caring for a child with a chronic illness. Historically, there have been variations over the clinical definition and diagnosis of atopic eczema. A UK Working Party has developed criteria for use in epidemiological studies, and these are now commonly used, although further validation is required. To qualify as a case of atopic eczema using these criteria, the person must have had an itchy skin condition in the past 12 months, plus three or more of the following: a history of flexural involvement (that is, affecting the bends of the elbows or behind the knees) a history of a generally dry skin a personal history of other atopic disease (in children younger than 4 years, a history of atopic disease in a first-degree relative may be included) visible flexural dermatitis as defined by a photographic protocol -nset before the age of 2 years (not used in children younger than 4 years). There is uncertainty and a lack of standardisation around clinical assessment of disease severity, both in practice and in trial settings. Although a number of scoring systems have been used to categorise the disease as mild, moderate or severe, usually by aggregating scores from a range of symptoms and disease characteristics, none of these scoring systems has been accepted as a 'gold standard' and there remains general debate over their use. Atopic eczema in childhood shows a reverse social class gradient, with higher rates in socioeconomically advantaged groups and smaller families. There is also evidence of variation in prevalence by region, with the highest rates recorded in the South East and industrialised Midlands, and the lowest rates in Wales and Scotland. Management of atopic eczema takes place predominantly in primary care, and aims to relieve symptoms and prevent complications such as infections until remission occurs. This management involves skin care, anti-inflammatory treatment, and the identification and avoidance of exacerbating factors. Providing people with good-quality information about these issues is essential to successfully managing and treating atopic eczema. Referral to secondary care is advised only if the condition is severe and has not responded to appropriate therapy. Emollients are a first-line therapy for atopic eczema and aim to retain the skin's barrier function (keeping water in and irritants or pathogens out) and to prevent painful cracking. Frequent and continuous use is recommended even in the absence of symptoms. Preparations available include bath oils, soap substitutes and moisturisers; generally the greasier the preparation, the better the effect, although people using very greasy products may consider them unacceptable. Topical corticosteroids are the first-line treatment for flare-ups of atopic eczema. In order to reduce exposure to topical corticosteroids, they are used only intermittently to control exacerbations. Treatment regimens for topical steroids vary with disease severity, with clinicians usually recommending use of the mildest potency products possible to treat the condition, in order to minimise the potential adverse effects. Emollients are used together with the topical corticosteroids. Where there are associated bacterial or fungal infections, corticosteroids are combined with other substances (such as antimicrobials or salicylic acid) in topical preparations. Other treatments for atopic eczema include antihistamines, topical immunomodulators (see Section 8), and wet wraps (when a layer of emollients with or without corticosteroids is applied to the skin and wrapped in wet bandages, followed by dry bandages, and left overnight), which may be used in an attempt to maximise the effect of treatment. Treatments of last resort in resistant severe cases include systemic corticosteroids, phototherapy and systemic use of immunosuppressants.# The technology Topical corticosteroids have anti-inflammatory and immunosuppressive effects. The mechanism of the anti-inflammatory activity of topical steroids in general is unclear, although various symptomatic components of the inflammatory pathway are known to be suppressed. Thirty preparations of topical corticosteroids are included in this appraisal (see Appendix D). Topical corticosteroids are classified according to their potency. This is determined by the amount of vasoconstriction a topical corticosteroid produces and the degree to which it inhibits inflammation (a more potent product increases suppression to the inflammatory pathway). In the UK, four potencies are recognised: mild, moderately potent, potent and very potent. Across the different potencies, products have different formulations and different strengths (for example, 0.025%, 0.1%, 0.5%) and are available in various preparations (for example, ointment, cream, lotion, foam). The most widespread side effect of topical corticosteroid treatment is skin atrophy, where the skin becomes thin and may become easily bruised. This is more likely to occur on areas where the skin is already thin, such as the face or flexures. Absorption is greatest in these areas and therefore the use of potent steroids on these sites should generally be avoided. The skin may recover gradually after stopping treatment, but the original structure may never return. Prolonged or excessive use of potent steroids causes the dermis to lose its elasticity and stretch marks (striae) to appear, which are permanent. Children, especially babies, are particularly susceptible to side effects. The more potent corticosteroids are contraindicated for infants less than 1 year old. For full details of side effects and contraindications, see the Summaries of Product Characteristics (SPCs) for the topical corticosteroids. Guidelines from the British Association of Dermatologists suggest that the best way of using topical corticosteroids is probably twice daily for 10–14 days when the eczema is active, followed by a 'holiday period' of emollients only. The National Prescribing Centre recommends that, in general practice, topical corticosteroids be used in short bursts (for 3–7 days) to treat exacerbations of disease. There are varying recommendations about the frequency of application. The British National Formulary (BNF) states that "corticosteroid preparations should normally be applied once or twice daily. It is not necessary to apply them more frequently". Although there are few empirical data to assess the patterns of prescribing with respect to frequency of application, it appears that a twice-daily regimen is the most widespread approach to the use of topical corticosteroids in atopic eczema. However, the SPCs for some of the topical corticosteroids indicate that some are licensed for more frequent use (up to four times a day), and two products are licensed for use only once a day in atopic eczema. For individual posologies, see Appendix D.# Evidence and interpretation The Appraisal Committee (Appendix A) considered evidence from a number of sources (Appendix B). The remit given to NICE by the Department of Health/Welsh Assembly Government was to advise on the clinical and cost effectiveness of once-daily use compared with more frequent use of same-potency topical corticosteroids in the treatment of people with atopic eczema. The evidence appraised was restricted to comparisons of topical corticosteroids for atopic eczema within the same potency class. # Clinical effectiveness The Assessment Report reviewed data from one systematic review and ten randomised controlled trials (RCTs) that examined frequency of application of topical corticosteroids of the same potency. No RCTs or clinical controlled trials of mild topical corticosteroids were identified. One RCT examined moderately potent corticosteroids, eight RCTs examined potent corticosteroids and one RCT examined very potent corticosteroids. The study setting was hospital or secondary care for four of the ten trials but was not reported in the remaining studies. The duration of treatment for the trials ranged from 7 days to 4 weeks. Quality of life and patient preference were not reported by any of the included trials. The Assessment Group concluded the systematic review was of good methodological quality. The systematic review included three RCTs (two trials examining potent topical corticosteroids and one examining very potent topical corticosteroids), all of which were included in the Assessment Report. The authors of the systematic review found that in none of the studies was more frequent application superior to once-daily application. They concluded that point estimates suggest that a small difference in favour of more frequent application cannot be excluded. The Assessment Group did not consider meta-analysis to be appropriate because of the clinical and statistical heterogeneity of the trials. ## Moderately potent preparations One RCT was identified that examined the frequency of application in moderately potent topical corticosteroids for atopic eczema; the study population was children. The Assessment Report stated that the study was small and the duration of treatment was 7 days; the study did not report the setting, how allocation to treatment groups occurred, blinding of either outcome assessors or patients, or the number of patients responding to the treatment. There was no statistically significant difference in severity of symptoms following treatment with once-daily versus twice-daily application of topical corticosteroids. Adverse effects were not reported. ## Potent preparations Eight RCTs were identified that examined frequency of application in potent topical corticosteroids for atopic eczema. Five of these compared the same active compound administered once and twice daily (four of these trials examined fluticasone propionate ). Three trials investigating potent topical corticosteroids compared different active compounds; these all compared a once-daily-only product, mometasone furoate, with other topical corticosteroids administered twice daily. Apart from two trials within this potency class, the Assessment Report considered the quality of reporting and the methodology of the included RCTs to be generally poor. For four of the studies, the study setting was hospital or secondary care but the setting was not reported in the remaining studies. Duration of treatment in the studies was up to either 3 or 4 weeks. Where reported, the studies included people who had moderate to severe atopic eczema, apart from one study that included adults with mild to moderate eczema. One other study did not report the minimum severity of eczema of the study population. Studies included children and adults, people aged over 12 years or 16 years, or adults only. Subgroup analyses of children aged 12 years or younger were reported for two trials. The studies measured effectiveness of the treatments using a variety of different outcome measures, most of which were subjective assessments by the investigator and/or patient. All studies apart from one reported the number of patients responding to treatment. However, response to treatment was defined in different ways by the studies. Two outcomes were considered in the Assessment Report: the number of patients with at least a good response or 50% improvement, and the number of patients whose eczema was rated cleared or controlled. Seven studies reported the number of patients with at least a good response, assessed by the investigator and/or patient, or at least 50% improvement by the end of 3 or 4 weeks. Six studies reported the number of patients with eczema that was rated as cleared/controlled or excellent after 3 or 4 weeks. Overall, studies found little difference in response to treatment between once-daily and twice-daily application of potent corticosteroids. Some statistically significant differences favouring twice-daily treatment were identified, but these were inconsistent between outcome assessors (physicians versus patients) and outcomes selected for analysis. Subgroup analysis of patients aged 12 years or younger produced similar findings to the main analysis. One study compared success rates between morning and evening application in the once-daily group (67% versus 78%, difference 11.3%; 95% confidence interval –4.6 to 27.2, p = 0.17). Despite finding a statistically significant difference between once-daily and twice-daily application, when assessed by the physician (but not when assessed by the patient), the difference between once-daily evening treatment and twice-daily application was not statistically significant (78% versus 84%, difference 5.9%; 95% CI –6.6 to 18.4, p = 0.33). None of the studies reported the use of a validated severity scale, and the clinical relevance of a change in severity is not clear. However, in one study, once-daily use of mometasone furoate, which is a once-daily-only product, was found to result in a greater percentage improvement in total atopic eczema scores than twice-daily betamethasone valerate at each assessment, (p < 0.01). Another study found an improvement in pruritus (p = 0.007) only, following mometasone furoate, compared with twice-daily hydrocortisone 17-butyrate. A third study comparing once-daily use of mometasone furoate with betamethasone dipropionate found no statistically significant differences in percentage reduction of severity for erythema, induration or pruritus. However, the Assessment Group stated that these three trials were all of poor quality because they were described as single-blind (investigators blinded), but the trials did not give details of methods or procedures, or use of placebo treatment in the once-daily group. Two of these trials also failed to report whether comparison groups were similar at baseline. A greater reduction in severity scores demonstrated at 2 weeks (p = 0.04) for twice-daily compared with once-daily use of hydrocortisone 17-butyrate was not maintained at 4 weeks (p = 0.08) in one trial, and although the twice-daily group showed more pronounced reductions in rating for erythema at 4 weeks (p = 0.03), this was not the case for the other symptoms assessed. No confidence intervals were available for these trials. One trial found total severity scores to be similar between once-daily and twice-daily application of fluticasone propionate ointment at each visit, although logistic regression analysis of total severity score (adjusting for age and baseline total severity score) favoured twice-daily application at the last visit attended (odds ratio 1.72; 95% CI 1.05 to 2.82, p = 0.033). However, the odds ratio for the treatment effect in the subgroup analysis of patients aged 12 years or younger was not statistically significant (OR 1.85; 95% CI 0.88 to 3.89, p = 1.03). None of the other studies comparing potent topical corticosteroids found a statistically significant difference in severity of atopic eczema following once-daily application compared with more frequent applications. The quality and extent of reporting of adverse effects was variable among studies. There appeared to be little difference in the frequency or severity of adverse events between once-daily and twice-daily application of topical corticosteroids, although data were limited because of the short duration of the studies. One study did report potential differences in sleep disturbance, finding sleep to be "as good as ever has been" or better by 37% of patients following once-daily application of fluticasone propionate compared with 55% of patients following twice-daily application. No p value or confidence intervals were available for this outcome. ## Very potent preparations One RCT compared once-daily application of halcinonide cream (0.1%) with three-times-daily application of the same product. The trial was double-blind, but the concealment of allocation was not reported. The duration of the study was a maximum of 3 weeks, or shorter if complete remission was obtained. The age range of patients, the study setting and the minimum severity of eczema for the included patients were not reported in the study. The study compared the response of similar lesions on each side of the patient. A better response (slightly superior or markedly superior) was observed following three-times-daily application. Overall, 32% of patients had a better clinical response to three-times-daily application, 21% had a better clinical response to once-daily application, and 47% had an equal response (p < 0.05), but no statistically significant difference was found in the number of patients with at least a good absolute therapeutic response. The authors of the study stated that the side effects were generally of a mild nature, the most common being burning, pruritus and erythema, with no difference in incidence between once-daily and three-times-daily regimens, and that no systemic effects were observed. However, the Assessment Report pointed out that no data were presented on adverse effects. ## Summary Overall, the Assessment Report did not identify any clear differences for any of the potency classes in outcomes between once-daily and more frequent application of topical corticosteroids. For potent preparations, one study indicated a statistically significant difference in favour of the twice-daily application of fluticasone propionate (ointment) in response rates between the different regimens (at least a good response rate or 50% improvement), when patients were assessed by physicians; however, this was not the case for patient assessment. For a response of cleared or controlled atopic eczema, one trial indicated a significant difference in favour of twice-daily treatment of hydrocortisone 17-butyrate when patients were assessed by a physician. Two studies, considered by the Assessment Group to be of poor quality (as described in Section 4.1.14), favoured once-daily treatment of mometasone furoate over twice-daily use of other products (depending on severity of certain symptoms). The trial of a very potent corticosteroid reported a statistically significant difference in clinical response, favouring more frequent application, but no significant difference in the number of patients with at least a good response. # Cost effectiveness The Assessment Group did not identify any published economic evaluations that examined frequency of use of same-potency topical corticosteroids. No economic evaluations were identified or submitted by the manufacturers or other consultees. No quality-of-life or patient preference outcomes were included in any of the studies in the systematic review. The Assessment Group concluded that there was no basis to draw firm conclusions over the relative effectiveness of once-daily versus more frequent use of same-potency topical corticosteroids for atopic eczema. Consequently, the economic analysis assumes equivalent effectiveness of once-daily application and more frequent application of topical corticosteroids, and cost-minimisation analysis was undertaken. The cost per application of topical corticosteroids varies depending on the quantity used per application. Evidence was derived from two of the included RCTs and four additional studies that were identified. The Assessment Group stated that, although it would be reasonable to assume that the actual amount of topical corticosteroid used in a once-daily regimen is less than that used for more frequent applications (especially when referring to the same product), it is not possible to estimate accurately the quantity of medication used according to frequency of application. Another consideration was that topical corticosteroids are applied when people experience flare-ups, rather than continuously over time. Consequently, extrapolation over longer periods of time was not straightforward. The Assessment Group provided a cost-minimisation analysis for nine of the ten included clinical trials. In this, once-daily use was the least costly option on six occasions and twice-daily use the least costly on three occasions. The wide range of topical corticosteroid products available and their varied prices means that there are many possible prescribing scenarios. The availability of specifically marketed once-daily topical corticosteroids, which are priced much higher than other generic and proprietary products, makes a once-daily regimen more costly when these products are used. For example, where fluticasone propionate cream (£4.59) or mometasone furoate (£4.22) once daily is substituted for betamethasone valerate (£1.31), betamethasone dipropionate (£2.05) or hydrocortisone butyrate (£2.38) twice daily, the once-daily regimen would be expected to cost more than the twice-daily regimen. The trial examining fluticasone propionate (ointment) showed a benefit associated with twice-daily use in terms of physician assessment (but not for patient assessment) of patients' target area of atopic eczema. Consequently, a simple estimate of cost effectiveness was made. This found the additional cost per treatment success to be £76.50. The assumptions underlying this analysis were generous and a more realistic estimate of the treatment cost per additional successfully treated flare-up would probably be half that value. The Assessment Group concluded that the greater likelihood of treatment success (that is, successfully treated flare-up) would be of sufficient value (in terms of patient benefit, and avoided GP consultations, referrals to specialists or prescribing of more expensive products) to regard twice-daily application as cost effective. # Consideration of the evidence The Committee reviewed the data available on the clinical and cost effectiveness of the frequency of application of topical corticosteroids for atopic eczema, having considered evidence on the nature of the condition and the value placed on the benefits of different frequencies of application of topical corticosteroids by people with atopic eczema, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources. The Committee considered the various factors that might influence the frequency of application of topical corticosteroids for atopic eczema. These included the clinical presentation, factors influencing concordance with treatment, and patient choice. It heard from the experts that the potency of corticosteroid was not a relevant factor in determining the frequency of application. Additionally, the Committee appreciated that people with eczema may have considerable fear of the use of corticosteroids, and also need to use a number of other measures to manage their condition on a daily basis. On the basis of expert testimony, concordance with once-daily or twice-daily application of topical corticosteroids is not of particular concern to patients because of the fact that they have to apply emollients regularly to manage their condition. The Committee was informed that good-quality patient education on the use of topical corticosteroids was a significant factor in ensuring the success of therapy. The Committee was also informed that there was a clear need for continuing education of healthcare professionals to ensure that correct advice on the use of topical corticosteroids is given to people with atopic eczema. The Committee reviewed the evidence related to the frequency of application of topical corticosteroids in atopic eczema. It considered that the RCTs available were, in general, of poor methodological quality, and it was advised by the experts that longer follow-up – months, not weeks – would be required of trials to assess fully any potential differences in long-term efficacy and adverse effects between once-daily and more frequent applications of topical corticosteroids. The Committee additionally appreciated that there may be differences in the pharmacokinetics of the individual topical corticosteroids, but it was persuaded that these differences, if of clinical significance, would be reflected in the clinical effectiveness evidence. The Committee was informed that differences exist in clinical practice, between clinicians, in the prescription of once-daily or more frequent use of topical corticosteroids. However, it was agreed by the experts that, where once-daily application of a topical corticosteroid was initially advised, clinicians would have to increase either the potency or the frequency of the topical corticosteroid, if there was no improvement in the condition. Alternatively, if twice-daily application was advised initially for a flare-up, it would be expected that people would reduce the frequency of application of the same product once their condition began to improve. Having considered the results from the RCTs, as well as the testimony from the expert witnesses, the Committee concluded that there was no compelling evidence of a clinically significant difference between once-daily application and more frequent application of topical corticosteroids in terms of their effectiveness, patient satisfaction, adverse events, concordance with therapy or the number of follow-up visits required. It was persuaded that current clinical practice would therefore support a recommendation for the use of topical corticosteroids no more frequently than twice daily. The Committee concluded that, on the basis of the consideration in Section 4.3.6, where more than one alternative topical corticosteroid is considered clinically appropriate within a potency class, the product with the lowest acquisition cost (taking into account pack size and frequency of application) should be used in preference to more expensive alternatives. From the cost-minimisation analysis presented, the Committee noted that because of the acquisition cost of some products licensed solely for once-daily application, in some product comparisons, twice-daily application of other products was less costly than once-daily application.# Recommendations for further research The trial literature is dominated by comparisons of differing frequency of use of fluticasone propionate (four trials) and comparisons of mometasone furoate with more traditional twice-daily treatment options (three trials). Trials are needed to establish whether once-daily use of the older (twice-daily) products is equivalent to more frequent use. Trials are also required to establish whether once-daily use of the older twice-daily products is equivalent to the once-daily-only products. Trials are required for all the potency classes, in particular for mild potency preparations, because no trials examining frequency of application of topical corticosteroids exist for this group. Robust trials are required that report quality-of-life data and patient preferences. Long-term follow-up is required in trials to assess adverse effects such as skin atrophy. The experts informed the Committee that there was a lack of support for people with the condition and inadequate information about the management of atopic eczema and the risks associated with the use of topical corticosteroids. Research should therefore be conducted to establish the most suitable method of conveying high-quality information to people with atopic eczema.# Implications for the NHS Information is not readily available on current prescribing patterns of topical corticosteroids in patients with atopic eczema. There is also limited information on the quantity of product used per treatment regimen. Consequently, it is not possible, with any certainty, to establish baseline information on which to base estimates of the resource impact of changes in prescribing between preparations of different acquisition costs. Furthermore, such cost savings will be relatively small at the patient level, and issues related to pack size and product waste can easily erode any potential cost saving. However, given the large patient group with atopic eczema, there may be opportunities for significant savings to the NHS on products prescribed, particularly at a primary care level, because this is where most prescribing of topical corticosteroids is likely to occur. An illustrative scenario is explored below. The estimate is based on a number of assumptions used in the calculations, and so should be interpreted cautiously. The underlying assumptions are that patients have two to four flare-ups a year, that they throw away any unused products after each flare-up, and that patients applying topical corticosteroids once daily would use either 50% or 75% of the amount they would use if they were applying the product twice daily. These potential savings assume that all the patient prescription costs are met by the NHS. In practice, however, many patients may receive only one prescription per year, because they may not discard their unused products. Consequently, the figures in the scenario below are likely to be an estimate of the maximum cost savings to the NHS. Where a prescribing practice of one of the newer once-daily-only products can appropriately be altered to twice-daily use of one of the older, cheaper topical corticosteroids of the same potency, cost savings have been estimated to range from £300,000 to £600,000 (excluding VAT) for a patient group of 100,000 people with atopic eczema.# Related guidance The Institute has issued guidance on the use of tacrolimus and pimecrolimus for atopic eczema (NICE technology appraisal 82)# Review of guidance The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review. The guidance on this technology will be reviewed in July 2007. Andrew DillonChief ExecutiveAugust 2004# Appendix C. Detail on criteria for audit of the frequency of application of topical corticosteroids for atopic eczema # Possible objectives for an audit An audit could be carried out to ensure the appropriateness of prescription of topical corticosteroids for atopic eczema. # Possible patients to be included in the audit An audit could be carried out on all patients seen for atopic eczema in a reasonable period for audit, for example, 6 months, who are prescribed topical corticosteroids but not those topical agents that combine corticosteroids with other active agents (for example, antimicrobials or salicylic acid). # Measures that could be used as a basis for an audit The measures that could be used in an audit of the prescription of topical corticosteroids for atopic eczema are shown in the table following. Criterion Standard Exception Definition of terms . Topical corticosteroids for atopic eczema are prescribed for application only once or twice daily % of people for whom topical corticosteroids for atopic eczema are prescribed None The diagnosis of atopic eczema is established by the person having an itchy skin condition in the past 12 months plus three or more of the following: history of flexural involvement (that is, affecting the bends of the elbow or behind the knees); history of a generally dry skin; personal history of other atopic disease (in children younger than 4 years, history of atopic disease in a first-degree relative may be included); visible flexural dermatitis as defined by a photographic protocol; and onset before the age of 2 years (not used in children younger than 4 years). For a list of preparations of topical corticosteroids that are relevant for this measure,seeAppendix D. . If more than one alternative topical corticosteroid is considered clinically appropriate within a potency class, the drug with the lowest acquisition cost is prescribed % of people who are prescribed topical corticosteroids for atopic eczema None Clinicians will need to agree locally on how the lowest acquisition cost is determined for audit purposes, taking into account pack size and frequency of application. See Appendix D for a list of preparations by potency class. # Calculation of compliance Compliance (%) with each measure described in the table above is calculated as follows. Number of patients whose care is consistent with the criterion plus number of patients who meet any exception listed x 100 Number of patients to whom the measure applies Clinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.# Appendix D. Topical corticosteroids for the treatment of atopic eczema, grouped by potency BNF chemical name Manufacturer Product name (®) Posology from SPCs, where available Net cost per 30 g/30 ml for each strength (does not include VAT or dispensing fee) Mild potency Hydrocortisone Alpharma BCM Specials Bell Sons & Co. (Druggists) Bioglan Laboratories Bioglan Pharmaceuticals Biorex Laboratories Co-Pharma Diomed Developments Galpharm Healthcare Lagap Pharmaceuticals Norton Pharmaceuticals Novartis Pinewood Laboratories Reckitt Benckiser Healthcare (UK) Roussel Laboratories Thornton & Ross Waymade Generic hydrocortisone cream 0.5%, 1%, ointment 0.5%, 1% N/A Hydrocortisone GlaxoSmithKline Efcortelan cream/ointment 0.5%, 1%, 2.5% –3 times daily Hydrocortisone Yamanouchi Mildison Lipocream 1% –3 times daily Hydrocortisone Dermal Dioderm cream 0.1% Twice daily Fluocinolone acetonide GP Pharma Synalar cream 1/10, 0.0025% –3 times daily Moderate potency Alclometasone dipropionate Pliva Modrasone cream/ointment 0.05% –3 times daily Betamethasone valerate GlaxoSmithKline Betnovate RD cream/ointment 0.025% –3 times daily Clobetasone butyrate GlaxoSmithKline Eumovate cream/ointment 0.05% Up to 4 times daily Desoximetasone Stiefel Stiedex LP oily cream 0.05% –3 times daily Fluocinolone acetonide GP Pharma Synalar cream/ointment 1/4, 0.00625% –3 times daily Fluocortolone Meadow Ultralanum Plain cream/ointment 0.25% N/A Fludroxycortide Typharm Haelan cream/ointment 0.0125% –3 times daily Potent Beclometasone dipropionate GlaxoSmithKline Propaderm cream/ointment 0.025% Twice daily Betamethasone dipropionate Schering Plough Diprosone cream/ointment 0.05%, lotion 0.05% –2 times daily Betamethasone valerate GlaxoSmithKline Betnovate cream/ointment 0.1%, lotion 0.1%, scalp application 0.1% –3 times daily Betamethasone valerate Celltech Bettamousse foam 0.12% Twice daily Betamethasone valerate Dermal Betacap scalp application 0.1% Twice daily Betamethasone valerate Dowelhurst, Futuna Generic betamethasone valerate cream 0.1%, ointment 0.1% N/A Diflucortolone valerate Meadow Nerisone cream/ointment 0.1%, oily cream 0.1% N/A Fluocinolone acetonide GP Pharma Synalar cream/ointment 0.025%, gel 0.025% –3 times daily Fluocinonide GP Pharma Metosyn FAPG cream 0.05%, ointment 0.05% –4 times daily Fluticasone propionate GlaxoSmithKline Cutivate cream 0.05% Once daily Fluticasone propionate GlaxoSmithKline Cutivate ointment 0.05% Twice daily Hydrocortisone butyrate Yamanouchi Locoid Lipocream 0.1% –3 times daily Hydrocortisone butyrate Yamanouchi Locoid cream/ointment 0.1%, scalp lotion 0.1% –4 times daily Hydrocortisone butyrate Yamanouchi Locoid Crelo 0.1% –3 times daily Mometasone furoate Schering Plough Elocon cream/ointment 0.1%, scalp lotion 0.1% Once daily Very potent Clobetasol propionate GlaxoSmithKline Dermovate cream/ointment 0.05%, scalp application 0.05% –2 times daily Diflucortolone valerate Schering Health/Meadow Nerisone Forte ointment/oily cream 0.3% N/A Halcinonide Bristol-Myers Squibb Halciderm cream 0.1% –3 times daily Taken from BNF 47 (March 2004) Using largest pack sizes available (for example, where 100 g is the largest pack size, the cost is calculated using the 100 g price multiplied by 0.3) N/A – not available# Changes after publication March 2014: minor maintenance March 2012: minor maintenance# About this guidance NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.	{'Guidance': 'This appraisal relates to the frequency of application of topical corticosteroids in the treatment of atopic eczema. It does not include the use of topical agents that combine corticosteroids with other active agents (for example, antimicrobials or salicylic acid).\n\nIt is recommended that topical corticosteroids for atopic eczema should be prescribed for application only once or twice daily.\n\nIt is recommended that where more than one alternative topical corticosteroid is considered clinically appropriate within a potency class, the drug with the lowest acquisition cost should be prescribed, taking into account pack size and frequency of application.', 'Clinical need and practice': "Atopic eczema (synonymous with atopic dermatitis) is a chronic relapsing skin condition characterised by intense itching, dry skin, redness, inflammation and exudation. It affects mainly the flexor surfaces of the elbows and knees, as well as the face and neck.\n\nThe term 'atopic' refers to the association with atopy (a state of hypersensitivity to common environmental allergens that may be inherited), and differentiates atopic eczema from other forms of eczema such as irritant, allergic contact, discoid, venous, seborrhoeic and photosensitive eczema, which have different disease patterns and aetiologies.\n\nEstimates of prevalence vary but suggest that the condition may affect as many as 15–20% of school-age children and 2–10% of adults. Most people with atopic eczema (more than 80%) experience mild disease; only around 2–4% of people with eczema have a severe form of the disease. Despite the lower prevalence, the presentation of disease in adults is often more severe and chronic in nature.\n\nIn most people with atopic eczema, the condition begins in early childhood – often in the first year of life – when it can be particularly severe. Findings from the National Child Development Study (NCDS), developed from the birth cohort of 1958, suggested an incidence of around 50 cases per 1000 in the first year of life, falling to 5 new cases per 1000 per year for the rest of childhood. In around 60% of children, the condition clears by the time they reach their teens. However, the tendency towards dry and irritable skin generally persists and later recurrences are common.\n\nThe aetiology of atopic eczema is complex and not fully understood. Genetic factors are important but environmental factors – such as house dust mites, pollen, tobacco, air pollution and low humidity – may cause its onset and/or exacerbate existing symptoms. More persistent disease has been consistently linked with early disease onset, severe widespread disease in early life, concomitant asthma or hay fever, and a family history of atopic eczema. The condition is exacerbated by soap and detergents, clothes containing wool or certain synthetic fibres, and extremes of temperature.\n\nThe severity of atopic eczema varies enormously, from an occasional dry, scaly patch to a debilitating disease, where much of the body is covered by excoriated, bleeding and infected lesions. Its course may be continuous for prolonged periods or of a relapsing–remitting nature, characterised by acute flare-ups.\n\nItching skin (pruritus) is a major symptom of atopic eczema. A vicious circle can occur, where itching and scratching damage the skin and increase inflammation, which in turn increases the itch. Damage to the skin from scratching can cause bleeding, secondary infection and thickening of the skin (lichenification).\n\nThe impact of atopic eczema on quality of life can be considerable, and varies according to disease severity. In addition to the burden imposed by daily treatment, studies have shown not only that the condition affects everyday activities such as work or school and social relationships, but also that people with atopic eczema may also experience anxiety, depression and other psychological problems. Sleep disturbance is common, especially during flare-ups, which in turn can lead to problems with irritability and lack of concentration. Severe atopic eczema in children can also have a significant impact on family life, with parents/carers having to cope with the demands associated with caring for a child with a chronic illness.\n\nHistorically, there have been variations over the clinical definition and diagnosis of atopic eczema. A UK Working Party has developed criteria for use in epidemiological studies, and these are now commonly used, although further validation is required. To qualify as a case of atopic eczema using these criteria, the person must have had an itchy skin condition in the past 12\xa0months, plus three or more of the following:\n\na history of flexural involvement (that is, affecting the bends of the elbows or behind the knees)\n\na history of a generally dry skin\n\na personal history of other atopic disease (in children younger than 4\xa0years, a history of atopic disease in a first-degree relative may be included)\n\nvisible flexural dermatitis as defined by a photographic protocol\n\nonset before the age of 2\xa0years (not used in children younger than 4\xa0years).\n\nThere is uncertainty and a lack of standardisation around clinical assessment of disease severity, both in practice and in trial settings. Although a number of scoring systems have been used to categorise the disease as mild, moderate or severe, usually by aggregating scores from a range of symptoms and disease characteristics, none of these scoring systems has been accepted as a 'gold standard' and there remains general debate over their use.\n\nAtopic eczema in childhood shows a reverse social class gradient, with higher rates in socioeconomically advantaged groups and smaller families. There is also evidence of variation in prevalence by region, with the highest rates recorded in the South East and industrialised Midlands, and the lowest rates in Wales and Scotland.\n\nManagement of atopic eczema takes place predominantly in primary care, and aims to relieve symptoms and prevent complications such as infections until remission occurs. This management involves skin care, anti-inflammatory treatment, and the identification and avoidance of exacerbating factors. Providing people with good-quality information about these issues is essential to successfully managing and treating atopic eczema. Referral to secondary care is advised only if the condition is severe and has not responded to appropriate therapy.\n\nEmollients are a first-line therapy for atopic eczema and aim to retain the skin's barrier function (keeping water in and irritants or pathogens out) and to prevent painful cracking. Frequent and continuous use is recommended even in the absence of symptoms. Preparations available include bath oils, soap substitutes and moisturisers; generally the greasier the preparation, the better the effect, although people using very greasy products may consider them unacceptable.\n\nTopical corticosteroids are the first-line treatment for flare-ups of atopic eczema. In order to reduce exposure to topical corticosteroids, they are used only intermittently to control exacerbations. Treatment regimens for topical steroids vary with disease severity, with clinicians usually recommending use of the mildest potency products possible to treat the condition, in order to minimise the potential adverse effects. Emollients are used together with the topical corticosteroids.\n\nWhere there are associated bacterial or fungal infections, corticosteroids are combined with other substances (such as antimicrobials or salicylic acid) in topical preparations.\n\nOther treatments for atopic eczema include antihistamines, topical immunomodulators (see Section 8), and wet wraps (when a layer of emollients with or without corticosteroids is applied to the skin and wrapped in wet bandages, followed by dry bandages, and left overnight), which may be used in an attempt to maximise the effect of treatment.\n\nTreatments of last resort in resistant severe cases include systemic corticosteroids, phototherapy and systemic use of immunosuppressants.", 'The technology': 'Topical corticosteroids have anti-inflammatory and immunosuppressive effects. The mechanism of the anti-inflammatory activity of topical steroids in general is unclear, although various symptomatic components of the inflammatory pathway are known to be suppressed.\n\nThirty preparations of topical corticosteroids are included in this appraisal (see Appendix D). Topical corticosteroids are classified according to their potency. This is determined by the amount of vasoconstriction a topical corticosteroid produces and the degree to which it inhibits inflammation (a more potent product increases suppression to the inflammatory pathway). In the UK, four potencies are recognised: mild, moderately potent, potent and very potent. Across the different potencies, products have different formulations and different strengths (for example, 0.025%, 0.1%, 0.5%) and are available in various preparations (for example, ointment, cream, lotion, foam).\n\nThe most widespread side effect of topical corticosteroid treatment is skin atrophy, where the skin becomes thin and may become easily bruised. This is more likely to occur on areas where the skin is already thin, such as the face or flexures. Absorption is greatest in these areas and therefore the use of potent steroids on these sites should generally be avoided. The skin may recover gradually after stopping treatment, but the original structure may never return. Prolonged or excessive use of potent steroids causes the dermis to lose its elasticity and stretch marks (striae) to appear, which are permanent. Children, especially babies, are particularly susceptible to side effects. The more potent corticosteroids are contraindicated for infants less than 1\xa0year old. For full details of side effects and contraindications, see the Summaries of Product Characteristics (SPCs) for the topical corticosteroids.\n\nGuidelines from the British Association of Dermatologists suggest that the best way of using topical corticosteroids is probably twice daily for 10–14\xa0days when the eczema is active, followed by a \'holiday period\' of emollients only. The National Prescribing Centre recommends that, in general practice, topical corticosteroids be used in short bursts (for 3–7\xa0days) to treat exacerbations of disease.\n\nThere are varying recommendations about the frequency of application. The British National Formulary (BNF) states that "corticosteroid preparations should normally be applied once or twice daily. It is not necessary to apply them more frequently". Although there are few empirical data to assess the patterns of prescribing with respect to frequency of application, it appears that a twice-daily regimen is the most widespread approach to the use of topical corticosteroids in atopic eczema. However, the SPCs for some of the topical corticosteroids indicate that some are licensed for more frequent use (up to four times a day), and two products are licensed for use only once a day in atopic eczema. For individual posologies, see Appendix D.', 'Evidence and interpretation': 'The Appraisal Committee (Appendix A) considered evidence from a number of sources (Appendix B). The remit given to NICE by the Department of Health/Welsh Assembly Government was to advise on the clinical and cost effectiveness of once-daily use compared with more frequent use of same-potency topical corticosteroids in the treatment of people with atopic eczema. The evidence appraised was restricted to comparisons of topical corticosteroids for atopic eczema within the same potency class.\n\n# Clinical effectiveness\n\nThe Assessment Report reviewed data from one systematic review and ten randomised controlled trials (RCTs) that examined frequency of application of topical corticosteroids of the same potency. No RCTs or clinical controlled trials of mild topical corticosteroids were identified. One RCT examined moderately potent corticosteroids, eight RCTs examined potent corticosteroids and one RCT examined very potent corticosteroids.\n\nThe study setting was hospital or secondary care for four of the ten trials but was not reported in the remaining studies. The duration of treatment for the trials ranged from 7\xa0days to 4\xa0weeks. Quality of life and patient preference were not reported by any of the included trials.\n\nThe Assessment Group concluded the systematic review was of good methodological quality. The systematic review included three RCTs (two trials examining potent topical corticosteroids and one examining very potent topical corticosteroids), all of which were included in the Assessment Report. The authors of the systematic review found that in none of the studies was more frequent application superior to once-daily application. They concluded that point estimates suggest that a small difference in favour of more frequent application cannot be excluded.\n\nThe Assessment Group did not consider meta-analysis to be appropriate because of the clinical and statistical heterogeneity of the trials.\n\n## Moderately potent preparations\n\nOne RCT was identified that examined the frequency of application in moderately potent topical corticosteroids for atopic eczema; the study population was children. The Assessment Report stated that the study was small and the duration of treatment was 7\xa0days; the study did not report the setting, how allocation to treatment groups occurred, blinding of either outcome assessors or patients, or the number of patients responding to the treatment. There was no statistically significant difference in severity of symptoms following treatment with once-daily versus twice-daily application of topical corticosteroids. Adverse effects were not reported.\n\n## Potent preparations\n\nEight RCTs were identified that examined frequency of application in potent topical corticosteroids for atopic eczema. Five of these compared the same active compound administered once and twice daily (four of these trials examined fluticasone propionate [ointment and cream]). Three trials investigating potent topical corticosteroids compared different active compounds; these all compared a once-daily-only product, mometasone furoate, with other topical corticosteroids administered twice daily.\n\nApart from two trials within this potency class, the Assessment Report considered the quality of reporting and the methodology of the included RCTs to be generally poor.\n\nFor four of the studies, the study setting was hospital or secondary care but the setting was not reported in the remaining studies. Duration of treatment in the studies was up to either 3 or 4\xa0weeks. Where reported, the studies included people who had moderate to severe atopic eczema, apart from one study that included adults with mild to moderate eczema. One other study did not report the minimum severity of eczema of the study population.\n\nStudies included children and adults, people aged over 12\xa0years or 16\xa0years, or adults only. Subgroup analyses of children aged 12\xa0years or younger were reported for two trials.\n\nThe studies measured effectiveness of the treatments using a variety of different outcome measures, most of which were subjective assessments by the investigator and/or patient. All studies apart from one reported the number of patients responding to treatment. However, response to treatment was defined in different ways by the studies. Two outcomes were considered in the Assessment Report: the number of patients with at least a good response or 50% improvement, and the number of patients whose eczema was rated cleared or controlled.\n\nSeven studies reported the number of patients with at least a good response, assessed by the investigator and/or patient, or at least 50% improvement by the end of 3 or 4\xa0weeks. Six studies reported the number of patients with eczema that was rated as cleared/controlled or excellent after 3 or 4\xa0weeks.\n\nOverall, studies found little difference in response to treatment between once-daily and twice-daily application of potent corticosteroids. Some statistically significant differences favouring twice-daily treatment were identified, but these were inconsistent between outcome assessors (physicians versus patients) and outcomes selected for analysis. Subgroup analysis of patients aged 12\xa0years or younger produced similar findings to the main analysis.\n\nOne study compared success rates between morning and evening application in the once-daily group (67% versus 78%, difference 11.3%; 95% confidence interval [CI] –4.6 to 27.2, p\xa0=\xa00.17). Despite finding a statistically significant difference between once-daily and twice-daily application, when assessed by the physician (but not when assessed by the patient), the difference between once-daily evening treatment and twice-daily application was not statistically significant (78% versus 84%, difference 5.9%; 95% CI –6.6 to 18.4, p\xa0=\xa00.33).\n\nNone of the studies reported the use of a validated severity scale, and the clinical relevance of a change in severity is not clear. However, in one study, once-daily use of mometasone furoate, which is a once-daily-only product, was found to result in a greater percentage improvement in total atopic eczema scores than twice-daily betamethasone valerate at each assessment, (p\xa0<\xa00.01). Another study found an improvement in pruritus (p\xa0=\xa00.007) only, following mometasone furoate, compared with twice-daily hydrocortisone 17-butyrate. A third study comparing once-daily use of mometasone furoate with betamethasone dipropionate found no statistically significant differences in percentage reduction of severity for erythema, induration or pruritus. However, the Assessment Group stated that these three trials were all of poor quality because they were described as single-blind (investigators blinded), but the trials did not give details of methods or procedures, or use of placebo treatment in the once-daily group. Two of these trials also failed to report whether comparison groups were similar at baseline.\n\nA greater reduction in severity scores demonstrated at 2\xa0weeks (p\xa0=\xa00.04) for twice-daily compared with once-daily use of hydrocortisone 17-butyrate was not maintained at 4\xa0weeks (p\xa0=\xa00.08) in one trial, and although the twice-daily group showed more pronounced reductions in rating for erythema at 4\xa0weeks (p\xa0=\xa00.03), this was not the case for the other symptoms assessed. No confidence intervals were available for these trials.\n\nOne trial found total severity scores to be similar between once-daily and twice-daily application of fluticasone propionate ointment at each visit, although logistic regression analysis of total severity score (adjusting for age and baseline total severity score) favoured twice-daily application at the last visit attended (odds ratio [OR] 1.72; 95% CI 1.05 to 2.82, p\xa0=\xa00.033). However, the odds ratio for the treatment effect in the subgroup analysis of patients aged 12\xa0years or younger was not statistically significant (OR 1.85; 95% CI 0.88 to 3.89, p\xa0=\xa01.03).\n\nNone of the other studies comparing potent topical corticosteroids found a statistically significant difference in severity of atopic eczema following once-daily application compared with more frequent applications.\n\nThe quality and extent of reporting of adverse effects was variable among studies. There appeared to be little difference in the frequency or severity of adverse events between once-daily and twice-daily application of topical corticosteroids, although data were limited because of the short duration of the studies.\n\nOne study did report potential differences in sleep disturbance, finding sleep to be "as good as ever has been" or better by 37% of patients following once-daily application of fluticasone propionate compared with 55% of patients following twice-daily application. No p value or confidence intervals were available for this outcome.\n\n## Very potent preparations\n\nOne RCT compared once-daily application of halcinonide cream (0.1%) with three-times-daily application of the same product.\n\nThe trial was double-blind, but the concealment of allocation was not reported. The duration of the study was a maximum of 3\xa0weeks, or shorter if complete remission was obtained. The age range of patients, the study setting and the minimum severity of eczema for the included patients were not reported in the study.\n\nThe study compared the response of similar lesions on each side of the patient. A better response (slightly superior or markedly superior) was observed following three-times-daily application. Overall, 32% of patients had a better clinical response to three-times-daily application, 21% had a better clinical response to once-daily application, and 47% had an equal response (p\xa0<\xa00.05), but no statistically significant difference was found in the number of patients with at least a good absolute therapeutic response.\n\nThe authors of the study stated that the side effects were generally of a mild nature, the most common being burning, pruritus and erythema, with no difference in incidence between once-daily and three-times-daily regimens, and that no systemic effects were observed. However, the Assessment Report pointed out that no data were presented on adverse effects.\n\n## Summary\n\nOverall, the Assessment Report did not identify any clear differences for any of the potency classes in outcomes between once-daily and more frequent application of topical corticosteroids. For potent preparations, one study indicated a statistically significant difference in favour of the twice-daily application of fluticasone propionate (ointment) in response rates between the different regimens (at least a good response rate or 50% improvement), when patients were assessed by physicians; however, this was not the case for patient assessment. For a response of cleared or controlled atopic eczema, one trial indicated a significant difference in favour of twice-daily treatment of hydrocortisone 17-butyrate when patients were assessed by a physician. Two studies, considered by the Assessment Group to be of poor quality (as described in Section 4.1.14), favoured once-daily treatment of mometasone furoate over twice-daily use of other products (depending on severity of certain symptoms). The trial of a very potent corticosteroid reported a statistically significant difference in clinical response, favouring more frequent application, but no significant difference in the number of patients with at least a good response.\n\n# Cost effectiveness\n\nThe Assessment Group did not identify any published economic evaluations that examined frequency of use of same-potency topical corticosteroids.\n\nNo economic evaluations were identified or submitted by the manufacturers or other consultees. No quality-of-life or patient preference outcomes were included in any of the studies in the systematic review.\n\nThe Assessment Group concluded that there was no basis to draw firm conclusions over the relative effectiveness of once-daily versus more frequent use of same-potency topical corticosteroids for atopic eczema. Consequently, the economic analysis assumes equivalent effectiveness of once-daily application and more frequent application of topical corticosteroids, and cost-minimisation analysis was undertaken.\n\nThe cost per application of topical corticosteroids varies depending on the quantity used per application. Evidence was derived from two of the included RCTs and four additional studies that were identified. The Assessment Group stated that, although it would be reasonable to assume that the actual amount of topical corticosteroid used in a once-daily regimen is less than that used for more frequent applications (especially when referring to the same product), it is not possible to estimate accurately the quantity of medication used according to frequency of application. Another consideration was that topical corticosteroids are applied when people experience flare-ups, rather than continuously over time. Consequently, extrapolation over longer periods of time was not straightforward.\n\nThe Assessment Group provided a cost-minimisation analysis for nine of the ten included clinical trials. In this, once-daily use was the least costly option on six occasions and twice-daily use the least costly on three occasions. The wide range of topical corticosteroid products available and their varied prices means that there are many possible prescribing scenarios. The availability of specifically marketed once-daily topical corticosteroids, which are priced much higher than other generic and proprietary products, makes a once-daily regimen more costly when these products are used. For example, where fluticasone propionate cream (£4.59) or mometasone furoate (£4.22) once daily is substituted for betamethasone valerate (£1.31), betamethasone dipropionate (£2.05) or hydrocortisone butyrate (£2.38) twice daily, the once-daily regimen would be expected to cost more than the twice-daily regimen.\n\nThe trial examining fluticasone propionate (ointment) showed a benefit associated with twice-daily use in terms of physician assessment (but not for patient assessment) of patients\' target area of atopic eczema. Consequently, a simple estimate of cost effectiveness was made. This found the additional cost per treatment success to be £76.50. The assumptions underlying this analysis were generous and a more realistic estimate of the treatment cost per additional successfully treated flare-up would probably be half that value. The Assessment Group concluded that the greater likelihood of treatment success (that is, successfully treated flare-up) would be of sufficient value (in terms of patient benefit, and avoided GP consultations, referrals to specialists or prescribing of more expensive products) to regard twice-daily application as cost effective.\n\n# Consideration of the evidence\n\nThe Committee reviewed the data available on the clinical and cost effectiveness of the frequency of application of topical corticosteroids for atopic eczema, having considered evidence on the nature of the condition and the value placed on the benefits of different frequencies of application of topical corticosteroids by people with atopic eczema, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources.\n\nThe Committee considered the various factors that might influence the frequency of application of topical corticosteroids for atopic eczema. These included the clinical presentation, factors influencing concordance with treatment, and patient choice. It heard from the experts that the potency of corticosteroid was not a relevant factor in determining the frequency of application.\n\nAdditionally, the Committee appreciated that people with eczema may have considerable fear of the use of corticosteroids, and also need to use a number of other measures to manage their condition on a daily basis. On the basis of expert testimony, concordance with once-daily or twice-daily application of topical corticosteroids is not of particular concern to patients because of the fact that they have to apply emollients regularly to manage their condition. The Committee was informed that good-quality patient education on the use of topical corticosteroids was a significant factor in ensuring the success of therapy. The Committee was also informed that there was a clear need for continuing education of healthcare professionals to ensure that correct advice on the use of topical corticosteroids is given to people with atopic eczema.\n\nThe Committee reviewed the evidence related to the frequency of application of topical corticosteroids in atopic eczema. It considered that the RCTs available were, in general, of poor methodological quality, and it was advised by the experts that longer follow-up – months, not weeks – would be required of trials to assess fully any potential differences in long-term efficacy and adverse effects between once-daily and more frequent applications of topical corticosteroids. The Committee additionally appreciated that there may be differences in the pharmacokinetics of the individual topical corticosteroids, but it was persuaded that these differences, if of clinical significance, would be reflected in the clinical effectiveness evidence.\n\nThe Committee was informed that differences exist in clinical practice, between clinicians, in the prescription of once-daily or more frequent use of topical corticosteroids. However, it was agreed by the experts that, where once-daily application of a topical corticosteroid was initially advised, clinicians would have to increase either the potency or the frequency of the topical corticosteroid, if there was no improvement in the condition. Alternatively, if twice-daily application was advised initially for a flare-up, it would be expected that people would reduce the frequency of application of the same product once their condition began to improve.\n\nHaving considered the results from the RCTs, as well as the testimony from the expert witnesses, the Committee concluded that there was no compelling evidence of a clinically significant difference between once-daily application and more frequent application of topical corticosteroids in terms of their effectiveness, patient satisfaction, adverse events, concordance with therapy or the number of follow-up visits required. It was persuaded that current clinical practice would therefore support a recommendation for the use of topical corticosteroids no more frequently than twice daily.\n\nThe Committee concluded that, on the basis of the consideration in Section 4.3.6, where more than one alternative topical corticosteroid is considered clinically appropriate within a potency class, the product with the lowest acquisition cost (taking into account pack size and frequency of application) should be used in preference to more expensive alternatives. From the cost-minimisation analysis presented, the Committee noted that because of the acquisition cost of some products licensed solely for once-daily application, in some product comparisons, twice-daily application of other products was less costly than once-daily application.', 'Recommendations for further research': 'The trial literature is dominated by comparisons of differing frequency of use of fluticasone propionate (four trials) and comparisons of mometasone furoate with more traditional twice-daily treatment options (three trials).\n\nTrials are needed to establish whether once-daily use of the older (twice-daily) products is equivalent to more frequent use.\n\nTrials are also required to establish whether once-daily use of the older twice-daily products is equivalent to the once-daily-only products.\n\nTrials are required for all the potency classes, in particular for mild potency preparations, because no trials examining frequency of application of topical corticosteroids exist for this group.\n\nRobust trials are required that report quality-of-life data and patient preferences.\n\nLong-term follow-up is required in trials to assess adverse effects such as skin atrophy.\n\nThe experts informed the Committee that there was a lack of support for people with the condition and inadequate information about the management of atopic eczema and the risks associated with the use of topical corticosteroids. Research should therefore be conducted to establish the most suitable method of conveying high-quality information to people with atopic eczema.', 'Implications for the NHS': 'Information is not readily available on current prescribing patterns of topical corticosteroids in patients with atopic eczema. There is also limited information on the quantity of product used per treatment regimen. Consequently, it is not possible, with any certainty, to establish baseline information on which to base estimates of the resource impact of changes in prescribing between preparations of different acquisition costs. Furthermore, such cost savings will be relatively small at the patient level, and issues related to pack size and product waste can easily erode any potential cost saving. However, given the large patient group with atopic eczema, there may be opportunities for significant savings to the NHS on products prescribed, particularly at a primary care level, because this is where most prescribing of topical corticosteroids is likely to occur.\n\nAn illustrative scenario is explored below. The estimate is based on a number of assumptions used in the calculations, and so should be interpreted cautiously. The underlying assumptions are that patients have two to four flare-ups a year, that they throw away any unused products after each flare-up, and that patients applying topical corticosteroids once daily would use either 50% or 75% of the amount they would use if they were applying the product twice daily. These potential savings assume that all the patient prescription costs are met by the NHS. In practice, however, many patients may receive only one prescription per year, because they may not discard their unused products. Consequently, the figures in the scenario below are likely to be an estimate of the maximum cost savings to the NHS.\n\nWhere a prescribing practice of one of the newer once-daily-only products can appropriately be altered to twice-daily use of one of the older, cheaper topical corticosteroids of the same potency, cost savings have been estimated to range from £300,000 to £600,000 (excluding VAT) for a patient group of 100,000 people with atopic eczema.', 'Related guidance': 'The Institute has issued guidance on the use of tacrolimus and pimecrolimus for atopic eczema (NICE technology appraisal 82)', 'Review of guidance': 'The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review.\n\nThe guidance on this technology will be reviewed in July 2007.\n\nAndrew DillonChief ExecutiveAugust 2004', 'Appendix C. Detail on criteria for audit of the frequency of application of topical corticosteroids for atopic eczema': '# Possible objectives for an audit\n\nAn audit could be carried out to ensure the appropriateness of prescription of topical corticosteroids for atopic eczema.\n\n# Possible patients to be included in the audit\n\nAn audit could be carried out on all patients seen for atopic eczema in a reasonable period for audit, for example, 6\xa0months, who are prescribed topical corticosteroids but not those topical agents that combine corticosteroids with other active agents (for example, antimicrobials or salicylic acid).\n\n# Measures that could be used as a basis for an audit\n\nThe measures that could be used in an audit of the prescription of topical corticosteroids for atopic eczema are shown in the table following.\n\nCriterion\n\nStandard\n\nException\n\nDefinition of terms\n\n. Topical corticosteroids for atopic eczema are prescribed for application only once or twice daily\n\n% of people for whom topical corticosteroids for atopic eczema are prescribed\n\nNone\n\nThe diagnosis of atopic eczema is established by the person having an itchy skin condition in the past 12\xa0months plus three or more of the following: history of flexural involvement (that is, affecting the bends of the elbow or behind the knees); history of a generally dry skin; personal history of other atopic disease (in children younger than 4\xa0years, history of atopic disease in a first-degree relative may be included); visible flexural dermatitis as defined by a photographic protocol; and onset before the age of 2\xa0years (not used in children younger than 4\xa0years).\n\nFor a list of preparations of topical corticosteroids that are relevant for this measure,seeAppendix D.\n\n. If more than one alternative topical corticosteroid is considered clinically appropriate within a potency class, the drug with the lowest acquisition cost is prescribed\n\n% of people who are prescribed topical corticosteroids for atopic eczema\n\nNone\n\nClinicians will need to agree locally on how the lowest acquisition cost is determined for audit purposes, taking into account pack size and frequency of application. See Appendix D for a list of preparations by potency class.\n\n# Calculation of compliance\n\nCompliance (%) with each measure described in the table above is calculated as follows.\n\nNumber of patients whose care is consistent with the criterion plus number of patients who meet any exception listed\n\n\n\nx 100\n\nNumber of patients to whom the measure applies\n\nClinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.', 'Appendix D. Topical corticosteroids for the treatment of atopic eczema, grouped by potency': 'BNF chemical name\n\nManufacturer\n\nProduct name (®)\n\nPosology from SPCs, where available\n\nNet cost[a] per 30\xa0g/30\xa0ml[b]\n \n \n \n for each strength (does not include VAT or dispensing fee)\n\nMild potency\n\nHydrocortisone\n\nAlpharma\n\nBCM Specials\n\nBell Sons & Co. (Druggists)\n\nBioglan Laboratories\n\nBioglan Pharmaceuticals\n\nBiorex Laboratories\n\nCo-Pharma\n\nDiomed Developments\n\nGalpharm Healthcare\n\nLagap Pharmaceuticals\n\nNorton Pharmaceuticals\n\nNovartis\n\nPinewood Laboratories\n\nReckitt Benckiser Healthcare (UK)\n\nRoussel Laboratories\n\nThornton & Ross\n\nWaymade\n\nGeneric hydrocortisone cream 0.5%, 1%, ointment 0.5%, 1%\n\nN/A\n\n£0.66, £0.74, £0.65, £0.76\n\nHydrocortisone\n\nGlaxoSmithKline\n\nEfcortelan cream/ointment 0.5%, 1%, 2.5%\n\n–3 times daily\n\n£0.66, £0.81, £1.83\n\nHydrocortisone\n\nYamanouchi\n\nMildison Lipocream 1%\n\n–3 times daily\n\n£2.63\n\nHydrocortisone\n\nDermal\n\nDioderm cream 0.1%\n\nTwice daily\n\n£2.69\n\nFluocinolone acetonide\n\nGP Pharma\n\n\n\nSynalar cream 1/10, 0.0025%\n\n–3 times daily\n\n£1.15\n\nModerate potency\n\nAlclometasone dipropionate\n\nPliva\n\nModrasone cream/ointment 0.05%\n\n–3 times daily\n\n£1.69\n\nBetamethasone valerate\n\nGlaxoSmithKline\n\nBetnovate RD cream/ointment 0.025%\n\n–3 times daily\n\n£1.08\n\nClobetasone butyrate\n\nGlaxoSmithKline\n\nEumovate cream/ointment 0.05%\n\nUp to 4 times daily\n\n£1.70\n\nDesoximetasone\n\nStiefel\n\nStiedex LP oily cream 0.05%\n\n–3 times daily\n\n£2.46\n\nFluocinolone acetonide\n\nGP Pharma\n\nSynalar cream/ointment 1/4, 0.00625%\n\n–3 times daily\n\n£1.22\n\nFluocortolone\n\nMeadow\n\nUltralanum Plain cream/ointment 0.25%\n\nN/A\n\n£1.77\n\nFludroxycortide\n\nTypharm\n\nHaelan cream/ointment 0.0125%\n\n–3 times daily\n\n£1.63\n\nPotent\n\nBeclometasone dipropionate\n\nGlaxoSmithKline\n\nPropaderm cream/ointment 0.025%\n\nTwice daily\n\n£1.74\n\nBetamethasone dipropionate\n\nSchering Plough\n\nDiprosone cream/ointment 0.05%, lotion 0.05%\n\n–2 times daily\n\n£2.05, £2.61\n\nBetamethasone valerate\n\nGlaxoSmithKline\n\nBetnovate cream/ointment 0.1%, lotion 0.1%, scalp application 0.1%\n\n–3 times daily\n\n£1.31, £1.57, £1.71\n\nBetamethasone valerate\n\nCelltech\n\nBettamousse foam 0.12%\n\nTwice daily\n\n£2.25\n\nBetamethasone valerate\n\nDermal\n\nBetacap scalp application 0.1%\n\nTwice daily\n\n£1.27\n\nBetamethasone valerate\n\nDowelhurst, Futuna\n\nGeneric betamethasone valerate cream 0.1%, ointment 0.1%\n\nN/A\n\n£1.54, £1.69\n\nDiflucortolone valerate\n\nMeadow\n\nNerisone cream/ointment 0.1%, oily cream 0.1%\n\nN/A\n\n£1.59, £2.56\n\nFluocinolone acetonide\n\nGP Pharma\n\nSynalar cream/ointment 0.025%, gel 0.025%\n\n–3 times daily\n\n£1.74, £2.57\n\nFluocinonide\n\nGP Pharma\n\nMetosyn FAPG cream 0.05%, ointment 0.05%\n\n–4 times daily\n\n£1.54, £1.52\n\nFluticasone propionate\n\nGlaxoSmithKline\n\nCutivate cream 0.05%\n\nOnce daily\n\n£4.59\n\nFluticasone propionate\n\nGlaxoSmithKline\n\nCutivate ointment 0.05%\n\nTwice daily\n\n£4.59\n\nHydrocortisone butyrate\n\nYamanouchi\n\nLocoid Lipocream 0.1%\n\n–3 times daily\n\n£2.38\n\nHydrocortisone butyrate\n\nYamanouchi\n\nLocoid cream/ointment 0.1%, scalp lotion 0.1%\n\n–4 times daily\n\n£2.27, £3.15\n\nHydrocortisone butyrate\n\nYamanouchi\n\nLocoid Crelo 0.1%\n\n–3 times daily\n\n£2.72\n\nMometasone furoate\n\nSchering Plough\n\nElocon cream/ointment 0.1%, scalp lotion 0.1%\n\nOnce daily\n\n£4.22, £4.88\n\nVery potent\n\nClobetasol propionate\n\nGlaxoSmithKline\n\n\n\nDermovate cream/ointment 0.05%, scalp application 0.05%\n\n–2 times daily\n\n£2.48, £3.27\n\nDiflucortolone valerate\n\nSchering Health/Meadow\n\nNerisone Forte ointment/oily cream 0.3%\n\nN/A\n\n£4.18\n\nHalcinonide\n\nBristol-Myers Squibb\n\nHalciderm cream 0.1%\n\n–3 times daily\n\n£3.40\n\n[a] Taken from BNF 47 (March 2004)\n\n[b] Using largest pack sizes available (for example, where 100 g is the largest pack size, the cost is calculated using the 100 g price multiplied by 0.3)\n\nN/A – not available', 'Changes after publication': 'March 2014: minor maintenance\n\nMarch 2012: minor maintenance', 'About this guidance': 'NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales.\n\nWe have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.'}	https://www.nice.org.uk/guidance/ta81	Evidence-based recommendations on using topical corticosteroids for people with atopic eczema.
68cf31c5a0d481513a3b343f83b39e912683ffdc	nice	Tacrolimus and pimecrolimus for atopic eczema	Tacrolimus and pimecrolimus for atopic eczema Evidence-based recommendations on tacrolimus (Protopic) and pimecrolimus (Elidel) for people with atopic eczema. # Guidance Topical tacrolimus and pimecrolimus are not recommended for the treatment of mild atopic eczema or as first-line treatments for atopic eczema of any severity. Topical tacrolimus is recommended, within its licensed indications, as an option for the second-line treatment of moderate to severe atopic eczema in adults and children aged 2 years and older that has not been controlled by topical corticosteroids (see Section 1.4), where there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy. Pimecrolimus is recommended, within its licensed indications, as an option for the second-line treatment of moderate atopic eczema on the face and neck in children aged 2 to 16 years that has not been controlled by topical corticosteroids (see Section 1.4), where there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy. For the purposes of this guidance, atopic eczema that has not been controlled by topical corticosteroids refers to disease that has not shown a satisfactory clinical response to adequate use of the maximum strength and potency that is appropriate for the patient's age and the area being treated. It is recommended that treatment with tacrolimus or pimecrolimus be initiated only by physicians (including general practitioners) with a special interest and experience in dermatology, and only after careful discussion with the patient about the potential risks and benefits of all appropriate second-line treatment options.# Clinical need and practice Atopic eczema (synonymous with atopic dermatitis) is a chronic relapsing skin condition characterised by intense itching, dry skin, redness, inflammation and exudation. It affects mainly the flexor surfaces of the elbows and knees, as well as the face and neck. The term 'atopic' refers to the association with atopy (a state of hypersensitivity to common environmental allergens that may be inherited) and differentiates atopic eczema from other forms of eczema such as irritant, allergic contact, discoid, venous, seborrhoeic and photosensitive eczema, which have different disease patterns and aetiologies. Estimates of prevalence vary but suggest that the condition may affect as many as 15–20% of school-age children and 2–10% of adults. The majority of people with atopic eczema (over 80%) experience mild disease, whereas only a small proportion (around 2–4%) have a severe form of the disease. Despite the lower prevalence, the presentation of disease in adults is often more severe and chronic in nature. In most people with atopic eczema, the condition begins in early childhood – often in the first year of life, when it can be particularly severe. Findings from the National Child Development Study, developed from the birth cohort of 1958, suggest an incidence of around 50 cases per 1000 in the first year of life, falling to 5 new cases per 1000 per year for the rest of childhood. In around 60% of children, the condition clears by the time they reach their teens. However, the tendency towards dry and irritable skin generally persists and later recurrences are common. The aetiology of atopic eczema is complex and not fully understood. Genetic factors are important but environmental factors, such as house dust mites, pollen, tobacco, air pollution and low humidity, may cause its onset and/or exacerbate existing symptoms. More persistent disease has been consistently linked with early disease onset, severe widespread disease in early life, concomitant asthma or hay fever, and a family history of atopic eczema. The condition is exacerbated by soap and detergents, clothes containing wool or certain synthetic fibres, and extremes of temperature. The severity of atopic eczema varies enormously, from an occasional dry, scaly patch to a debilitating disease where much of the body is covered by excoriated (scratched and abraded), bleeding and infected lesions. Its course may be continuous for prolonged periods or of a relapsing–remitting nature characterised by acute flare-ups. Itching skin (pruritus) is a major symptom of atopic eczema. A vicious circle can occur, where itching and scratching damage the skin and increase inflammation, which in turn increases the itch. Scratching can damage the skin and cause bleeding, secondary infection and thickening of the skin (lichenification). The impact of atopic eczema on quality of life can be considerable and it has been shown to vary according to disease severity. In addition to the burden of daily treatment, studies have shown not only that the condition may affect everyday activities, such as work or school, and social relationships, but also that people with atopic eczema may experience anxiety, depression and other psychological problems. Sleep disturbance is common, especially during flare-ups, which in turn can lead to problems with irritability and lack of concentration. Severe atopic eczema in children can also have a significant impact on family life, with parents/carers having to cope with the demands associated with caring for a child with a chronic illness. Historically, there have been variations in the clinical definition and diagnosis of atopic eczema. A UK Working Party has developed criteria for use in epidemiological studies, and these are now commonly used, although further validation is required. To qualify as a case of atopic eczema using these criteria, the person must have had an itchy skin condition in the last 12 months, plus three or more of the following criteria: a history of flexural involvement (that is, affecting the bends of the elbows or behind the knees) a history of a generally dry skin a personal history of other atopic disease (in children under 4 years, a history of atopic disease in a first-degree relative may be included) visible flexural dermatitis as defined by a photographic protocol -nset at younger than age 2 years (not used in children under 4 years). There is uncertainty and a lack of standardisation around clinical assessment of disease severity, both in practice and in trial settings. Although a number of scoring systems have been used to categorise the disease as mild, moderate or severe, usually by aggregating scores from a range of symptoms and disease characteristics, none of these scoring systems has been accepted as a 'gold standard' and there is still general debate over their use. Atopic eczema in childhood shows a reverse social class gradient, with higher rates in socio-economically advantaged groups and smaller families. There is also evidence of variation in prevalence by region, with the highest rates recorded in the South East and industrialised Midlands, and the lowest rates in Wales and Scotland. Management of atopic eczema takes place predominantly in primary care, and aims to relieve symptoms and prevent complications such as infection until remission occurs. This management involves the identification and avoidance of exacerbating factors, skin care and anti-inflammatory treatment. Providing people with good-quality information about these issues is essential to successfully managing and treating atopic eczema. Referral to secondary care is only advised if the condition is severe and has not responded to appropriate therapy. Emollients form a standard part of skin care and aim to retain the skin's barrier function (keeping water in and irritants or pathogens out) and prevent painful cracking. Frequent and continuous use is recommended even in the absence of symptoms. Preparations include bath oils, soap substitutes and moisturisers. Topical corticosteroids are the first-line treatment for episodic worsening (flare-ups) of atopic eczema. In order to reduce exposure to topical corticosteroids, they are used only intermittently to control exacerbations. Emollients are used with the topical corticosteroids. Topical corticosteroids are classified according to their potency. This is determined by the amount of vasoconstriction a topical corticosteroid produces and the degree to which it inhibits inflammation (a more potent product increases suppression to the inflammatory pathway). In the UK, four potencies are recognised: mild, moderately potent, potent and very potent. Across the different potencies, products have different formulations and different strengths (for example, 0.025%, 0.1%, 0.5%) and are available in various preparations (for example, ointment, cream, lotion, foam). Treatment regimens for topical corticosteroids vary with disease severity, with clinicians usually recommending use of the mildest potency products possible to treat the condition, in order to minimise the potential adverse effects. One of the potential long-term effects of topical corticosteroid treatment is skin atrophy, whereby the skin becomes thin and loses some of its function. This is more likely to occur in areas where the skin is already thin, such as the face and flexures. Although reversible in the short term, prolonged exposure can lead to permanent damage. Signs of atrophy include telangiectasia (abnormal dilation of capillary vessels and arterioles), increased transparency and shininess of the skin, and the appearance of striae (stripes or lines in the skin distinguished from surrounding tissue by colour, texture or elevation). Long-term use of topical corticosteroids on the eyelids has also been associated with the development of glaucoma. Systemic adverse effects with topical corticosteroids are rare but include suppression of the pituitary–adrenal axis (which may restrict growth). Absorption of topical corticosteroids is higher at certain sites such as the face and flexures, and potent topical corticosteroids are generally avoided in these areas. The more potent topical corticosteroids are also contraindicated in infants younger than 1 year and are avoided in children or used with great care and for short periods. A potent or moderately potent topical corticosteroid may be appropriate for severe atopic eczema on the limbs, but for 1–2 weeks only, followed by a weaker preparation as the condition improves. In resistant severe cases, treatment with systemic corticosteroids, phototherapy and systemic use of immunosuppressants, such as ciclosporin, may be required.# The technologies Tacrolimus and pimecrolimus are members of a new class of topical immunomodulators and belong to the class of immunosuppressant drugs known as calcineurin inhibitors. They work mainly by reducing inflammation through the suppression of T-lymphocyte responses, a different mechanism of action to topical corticosteroids. Although tacrolimus and pimecrolimus have similar mechanisms of action, they have different licensed indications (see Sections 3.1 and 3.2). # Tacrolimus Tacrolimus ointment (Fujisawa) is available in two strengths (0.1% and 0.03%), both of which are licensed for the treatment of moderate to severe atopic eczema in adults (16 years and above) who have not adequately responded to, or are intolerant of, conventional therapies. The lower strength is also licensed for the treatment of moderate to severe atopic eczema in children aged 2 years and older whose condition has not responded adequately to conventional therapies. The Summary of Product Characteristics states that tacrolimus should "be prescribed by physicians with experience in the treatment of atopic dermatitis". Tacrolimus is applied as a thin layer to affected areas of the skin twice daily and may be used on any part of the body, including the face, neck and flexural areas. The Summary of Product Characteristics states that the treatment of each affected region of the skin should be continued until the area is clear, and then be discontinued. It also states that treatment for adults should be started with 0.1% tacrolimus twice a day, that twice-daily treatment with 0.1% tacrolimus should be restarted if symptoms recur, and that an attempt should be made to reduce the frequency of application or to use the lower strength 0.03% tacrolimus if the clinical condition allows. For children, only the 0.03% strength is licensed, and the Summary of Product Characteristics states that the frequency of application should be reduced to once a day after a maximum of 3 weeks. Tacrolimus can be used for short-term and intermittent long-term treatment. The net price is £21.60 for 30 g and £41.04 for 60 g (0.1% tacrolimus) and £19.44 for 30 g and £36.94 for 60 g (0.03% tacrolimus) (British National Formulary, 46th edition). Costs may vary in different settings because of negotiated procurement discounts. Side effects include a burning or tingling sensation, pruritus, erythema, folliculitis, herpes simplex infection, acne, increased sensitivity to hot and cold, and alcohol intolerance. Lymphadenopathy has also been reported. The Summary of Product Characteristics states that before commencing treatment with tacrolimus, clinical infections at treatment sites should be cleared. It also states that emollients should not be applied to the same area within 2 hours of applying tacrolimus. When taken orally for other indications, tacrolimus has a number of well-recognised adverse effects, including renal toxicity and hypertension. The Summary of Product Characteristics states that, beyond 4 years of treatment, the potential for local immunosuppression (possibly resulting in infections or cutaneous malignancies) is unknown. For full details of side effects and contraindications, see the Summary of Product Characteristics. # Pimecrolimus Pimecrolimus cream 1.0% (Novartis) is licensed in patients with mild to moderate atopic eczema aged 2 years and older, for short-term treatment of signs and symptoms and intermittent long-term treatment to prevent flare-ups. Pimecrolimus is applied as a thin layer to affected skin twice daily and may be used on all skin areas, including the head, face, neck and intertriginous areas (where opposing skin surfaces touch and may rub, such as skin folds of the groin, axillae and breasts). The treatment of each affected region of the skin is continued until the area is clear and is then discontinued. Because of the low level of systemic absorption, there are no restrictions on the total daily dose applied, the body surface area that can be treated or the duration of treatment. The Summary of Product Characteristics states that emollients can be applied immediately after using pimecrolimus. The net price is £19.69 for 30 g, £37.41 for 60 g and £59.07 for 100 g (British National Formulary, 46th edition). Costs may vary in different settings because of negotiated procurement discounts. Side effects include a burning sensation, pruritus, erythema, skin infections (including folliculitis and rarely impetigo, herpes simplex and zoster and molluscum contagiosum), papilloma (rarely) and local reactions such as pain, paraesthesia, peeling, dryness, oedema and worsening of eczema. The Summary of Product Characteristics states that pimecrolimus should not be applied to areas affected by acute cutaneous viral infections, and that before commencing treatment with pimecrolimus, clinical infections at treatment sites should be cleared. It also states that long-term effect on the local skin immune response and on the incidence of skin malignancies is unknown. For full details of side effects and contraindications, see the Summary of Product Characteristics.# Evidence and interpretation The Appraisal Committee (Appendix A) considered evidence from a number of sources (Appendix B). # Clinical effectiveness Ten randomised controlled trials (RCTs) of tacrolimus and eight RCTs of pimecrolimus for the treatment of atopic eczema were considered. In most of the studies, comparators were topical corticosteroids or vehicle (a placebo consisting of the base cream or ointment without the active ingredient). Effectiveness was assessed in different ways across the trials, but common measures included the following: changes in severity using the Eczema Area Severity Index (EASI) or modified Eczema Area Severity Index (mEASI), which are well established assessment tools that account for individual symptoms and disease severity in four predefined regions of the body the Investigator's Global Assessment (IGA), a physician's rating scale based on interpretation of signs of eczema the Physician's Global Evaluation (PGE) of treatment success, which estimates the percentage change in the condition since the person was last seen the physician's evaluation of reduction in affected body surface area (BSA) patient-based measures such as number of flare-ups, pruritus and use of alternative treatments, such as topical corticosteroids.The main quality-of-life measure used in the trials was the Dermatology Life Quality Index (DLQI), which is a 10-item, self-administered questionnaire designed to measure the impact of skin diseases on patients' lives over the previous week. ## Tacrolimus Of the ten RCTs of tacrolimus, four were conducted in children and six in adults, all in populations with moderate to severe disease, reflecting the licensed indications. Two of the studies in children compared tacrolimus with mild topical corticosteroids (n = 374 and n = 417 ) and two compared it with vehicle (n = 180 and n = 352). Results were considered for 0.03% tacrolimus only, because 0.1% tacrolimus is not licensed for use in children. No trials in children have compared tacrolimus with potent or moderately potent topical corticosteroids. Three of the RCTs in adults used potent topical corticosteroid regimens as a comparator (n = 181, n = 570 and n = 975) and three used vehicle (n = 14, n = 215 and n = 632). For children, a pooled analysis of two studies that compared 0.03% tacrolimus with mild topical corticosteroids showed 0.03% tacrolimus to be more effective at 3 weeks, as measured by an improvement of at least 90% ('cleared' to 'excellent improvement') in the PGE (relative risk 2.56, 95% confidence interval 1.95 to 3.36). Based on the median improvement in mEASI score, both studies also showed 0.03% tacrolimus to be statistically significantly more effective than mild topical corticosteroids. Both studies in children comparing 0.03% tacrolimus and vehicle found tacrolimus to be more effective using the PGE categories of 'cleared' to 'marked improvement' (56.5% vs 15.7% in the larger study and 69.0% vs 38.0% in the smaller study for 0.03% tacrolimus vs vehicle). Statistically significant differences were also demonstrated for a number of other measures, including changes in EASI score, pruritus score and patient reports of 'feeling better'. Loss to follow-up was higher in the vehicle arms of the trials (56.0% vs 17.0% in the larger study and 15.9% vs 8.1% in the smaller study). For adults, a pooled analysis of two studies (n = 181 and n = 570) comparing 0.1% tacrolimus and potent topical corticosteroids found no statistically significant difference in the proportions of people with an improvement of at least 75% on the PGE ('cleared' to 'marked improvement') at 3 weeks (RR 1.08, 95% CI 0.97 to 1.21). The pooled analysis did not include the largest study (n = 975), which compared 0.1% tacrolimus with mild topical corticosteroids on the face and with potent topical corticosteroids on the body. Overall, this study found a greater improvement on the PGE with tacrolimus (62.9% vs 40.7% at 3 months, difference = 22.2%, 95% CI 16.1 to 28.4). This study reported other statistically significant differences favouring tacrolimus compared with a topical corticosteroid regimen. This included a higher proportion of people achieving an improvement in mEASI by at least 60% at 3 months (the primary outcome), a greater median improvement in mEASI (83.3% vs 76.9% at 3 months, p < 0.001; also statistically significant at 4 and 6 months, 95% CIs not stated), a greater reduction in the affected BSA, and a greater proportion of people 'feeling better'. However, there was a high loss to follow-up (25.5% with tacrolimus and 42.1% with topical corticosteroids). The other two studies that compared 0.1% tacrolimus and potent topical corticosteroids in adults did not report any statistically significant differences, although the larger of the two (n = 570) found smaller improvements in median mEASI score with 0.03% tacrolimus compared with potent topical corticosteroids (71% vs 83%, p < 0.05). Loss to follow-up in this study was 11.5% with tacrolimus and 9.1% with topical corticosteroids. Compared with vehicle, treatment of adults with tacrolimus was shown to be statistically significantly more effective using a number of outcome measures, including the PGE categories of 'cleared' to 'marked improvement', reduction in BSA affected, and improvement in EASI score. Loss to follow-up was noticeably high in the vehicle arms of the trials (68.4% vs 26.7% and 38.9% vs 13.2% in the two largest trials). Quality of life measures were reported by one study with an active comparator (n = 975) and one vehicle-controlled study in which participants were drawn from subsets of the largest studies of adults and children (n = 985). Both studies measured quality of life using the DLQI. Compared with a topical corticosteroid regimen (potent topical corticosteroid on the body and mild topical corticosteroid on the face), greater percentage improvements were found with 0.1% tacrolimus (66.7% vs 58.5% at 3 months and 74.3% vs 69.2% at 6 months, statistical significance was not reported), although the results for the different dimensions of 'quality of life' were not reported separately. Compared with vehicle, both strengths of tacrolimus were associated with greater improvements across all measurement dimensions in adults (symptoms and feelings, daily activities, leisure, work/school, personal relations, treatment ). In children (using the Children's DLQI completed by children with help from parents/guardians), greater improvements were found with 0.03% tacrolimus than with vehicle across all measurement dimensions except one (the personal relationships dimension ) and across all dimensions for toddlers (using the CDLQI for toddlers completed by parents/guardians ). For adverse effects, pooled analyses showed no statistically significant differences in skin infection rates between tacrolimus and topical corticosteroids. However, there was more skin burning in children with 0.03% tacrolimus compared with mild topical corticosteroids (RR 1.97, 95% CI 1.25 to 3.11) and in adults with 0.1% tacrolimus compared with potent topical corticosteroid regimens (RR 4.17, 95% CI 3.36 to 5.18). Withdrawal because of adverse effects was similar for tacrolimus and topical corticosteroids (1.6% to 3.9% of the tacrolimus group vs 1.6% to 3.3% of those using topical corticosteroids) but was consistently higher in the vehicle arms of the trials (4.5% to 12.3% with vehicle vs 2.9% to 5.7% with tacrolimus). Overall, tacrolimus is more effective in treating moderate to severe disease in adults and children than vehicle alone. In children, a number of measures of treatment effect suggest that tacrolimus is also more effective than mild topical corticosteroids but no trials have compared it with more potent topical corticosteroids. In adults, compared with topical corticosteroids, 0.1% tacrolimus was statistically significantly more effective in one study (n = 975) but not statistically significantly different in the other two studies (n = 570 and n = 181). ## Pimecrolimus Of the eight RCTs of pimecrolimus, three were conducted in children and five in adults. Three of the studies were provided by the manufacturer as commercial in confidence (two studies in adults and one study in children). None of the RCTs in children compared pimecrolimus with topical corticosteroids. Two studies used vehicle as a comparator (n = 403 and n = 713 ) and one compared pimecrolimus with 0.03% tacrolimus (provided in confidence by the manufacturer ). Two of the RCTs in adults used potent topical corticosteroids as a comparator (n = 260 and n = 658); the larger of these two RCTs was provided in confidence by the manufacturer. Three studies used vehicle as a comparator (n = 34, n = 192 and n = 260). A further vehicle-controlled study was provided in confidence by the manufacturer (n = 200). One of the studies in children (n = 713) and one in adults (n = 192) permitted the use of moderately potent topical corticosteroids to treat flare-ups in the treatment and control groups. Three of the studies in adults were conducted in people with moderate to severe disease, which does not match the licensed indication (see Section 3.2.1). They were included in the review for pragmatic reasons – firstly, on the basis of expert advice that there is considerable overlap between categories of eczema severity and, secondly, because of the limited evidence available from studies comparing pimecrolimus with an active treatment. Compared with potent topical corticosteroids, evidence from the smaller study suggests that pimecrolimus is less effective in treating moderate to severe atopic eczema. This study included four strengths of pimecrolimus (0.05%, 0.2%, 0.6% and 1.0%) but only the results for 1.0% pimecrolimus are presented, reflecting the product licence (see Section 3.2.1). Fewer people treated with pimecrolimus were judged to have 'clear' or 'almost clear' eczema at 3 weeks using the IGA score (11.1% vs 50.0%, difference = 38.9%, 95% CI 21 to 56). The study also reported a smaller percentage reduction in EASI for those using pimecrolimus (47.0% vs 78.0%, statistical significance was not reported) and that fewer people treated with pimecrolimus had mild or absent pruritus (46.7% vs 81.0%, difference = 34.3%, 95% CI 15.5 to 53.1, p < 0.05). The risk of skin burning was greater with pimecrolimus (RR 5.26, 95% CI 1.97 to 14.0). However, almost a quarter of participants were lost to follow-up (23.5%). Compared with vehicle, pooled analyses of studies in children with mild to moderate disease and in adults with moderate to severe disease showed that treatment with pimecrolimus resulted in better IGA scores at 3 and 6 weeks (RR 4.47, 95% CI 1.40 to 14.27 ; RR 1.87, 95% CI 1.26 to 2.76 ) and fewer flare-ups at 6 months (RR 1.78, 95% CI 1.10 to 2.86). People using pimecrolimus were less likely to use additional treatment with topical corticosteroids (RR 1.82, 95% CI 1.51 to 2.21) and pruritus was more often absent or mild at 3 and 6 weeks among the pimecrolimus group (RR at 3 weeks 1.99, 95% CI 1.53 to 2.58). Results from individual studies showed that pimecrolimus was statistically significantly more effective than vehicle using other measures of treatment effect, such as changes in EASI score and reduction in BSA affected. Quality of life for people treated with pimecrolimus was reported by one comparison with vehicle in adults (n = 192) and for a subset of participants from the smaller study in children (n = 241). The study in adults reported changes in two quality of life measures (the Quality of Life Index – Atopic Dermatitis and the DLQI) and found greater improvements among patients using pimecrolimus compared with those using vehicle for both measures (25.6% vs 7.4%, p = 0.002 and 22% vs 6.7%, p = 0.01). The study in children, which used the Parent's Index of QOL in Atopic Dermatitis, also reported a higher quality of life with pimecrolimus (p = 0.023). For adverse effects, a pooled analysis showed no statistically significant differences in rates of bacterial infection and skin burning between pimecrolimus and vehicle, but there was a greater risk of viral skin infection with pimecrolimus (12% vs 6%, RR 1.97, 95% CI 1.21 to 3.19). Overall, studies found pimecrolimus to be more effective at treating atopic eczema in adults and children than was vehicle alone. There is limited evidence on the effectiveness of pimecrolimus compared with topical corticosteroids. # Cost effectiveness The Committee considered economic analyses submitted by the manufacturers of both products and a model developed by the Assessment Group. There was only one relevant published economic analysis and this was conducted from the perspective of the US healthcare system and had methodological problems that limited its value. The Assessment Group analysis consisted of eight separate models, each relating to different cohorts of people with atopic eczema. ## Tacrolimus For the analysis of cost effectiveness in children, the Assessment Group model was run over 14 years to incorporate the possibility of disease resolution. All patients were assumed to be aged 2 years on entering. The model estimated that the costs per additional quality-adjusted life year (QALY) of first- and second-line treatment of eczema on the body were £9100 and £14,200, respectively, relative to the standard practice of using topical corticosteroids alone. For eczema in sensitive areas (on the face or in areas such as the armpits or groin where the treatment options are more limited because of concerns about skin atrophy), the costs per additional QALY were higher. First-line treatment cost £35,700 per additional QALY and second-line treatment was dominated by topical corticosteroids (that is, tacrolimus was both less effective and more costly than topical corticosteroids). In adults, the cost per additional QALY of first-line treatment of eczema on the body with tacrolimus was £37,400 relative to standard treatment with topical corticosteroids. Second-line treatment of 'body' eczema with tacrolimus cost less than topical corticosteroids alone but also conferred fewer QALYs. For eczema in sensitive areas (see Section 4.2.1.1), the cost per additional QALY of first-line treatment with tacrolimus was £11,900, and second-line treatment with tacrolimus was dominated by topical corticosteroids. Using a lower estimate of the amount of tacrolimus ointment used (2.3 g per day rather than 6.8 g per day) for adults reduced the incremental cost effectiveness ratio (ICER) for the treatment of 'body' eczema with tacrolimus (first-line) to £30,300 per QALY. Second-line treatment of 'body' eczema with tacrolimus still cost less than topical corticosteroids alone whilst also conferring fewer QALYs. The ICER for first-line treatment of eczema in sensitive areas (see Section 4.2.1.1) was also lower (£7000 per QALY), but tacrolimus as a second-line treatment continued to be dominated by topical corticosteroids. Overall, tacrolimus (first- and second-line) was estimated to be more costly than topical corticosteroids alone in all cases except one (second-line treatment of 'body' eczema in adults), whilst absolute differences in QALYs were very small. The Assessment Group also performed probabilistic analyses. The base-case results of all the Assessment Group's models were shown to be associated with considerable uncertainty, due mainly to the very small incremental benefits predicted. The manufacturer provided a cost-effectiveness analysis, in terms of disease-controlled days (DCDs), and compared treatment with tacrolimus (0.1% in adults, and 0.1% and 0.03% in children) after topical corticosteroids (potent topical corticosteroids as comparator for 0.1% tacrolimus, mild topical corticosteroids as comparator for 0.03% tacrolimus) with treatment with tacrolimus before topical corticosteroids in a hospital outpatient setting. The model adopted a semi-Markov approach, organised in four arms (topical corticosteroids in moderate or severe disease and tacrolimus in moderate or severe disease), and each one included four states of progression of atopic eczema (cleared or virtually cleared, moderately controlled, uncontrolled and flare-up). Each arm was run for 27 weeks (adults) or 15 weeks (children), corresponding to the duration of follow-up in the RCTs from which the effectiveness estimates were derived (scenario 1). In a second scenario, the model was run for 51 weeks on the basis of effectiveness estimates obtained from experts, and ciclosporin was included as a comparator for adults with severe eczema. A modified NHS and Personal and Social Services perspective was adopted, including work days lost. The results were presented as average cost-effectiveness ratios rather than ICERs. The Assessment Group calculated ICERs using the data provided by the manufacturer. For children with moderate disease, results from scenario 1 showed that 0.03% tacrolimus was dominated by both topical corticosteroids and 0.1% tacrolimus (that is, it produced fewer DCDs and was more costly than topical corticosteroids and 0.1% tacrolimus) and that 0.1% tacrolimus produced more DCDs than topical corticosteroids but was also more costly (the cost per additional DCD with 0.1% tacrolimus relative to topical corticosteroids was £16.40). In contrast, for children with severe disease, 0.1% tacrolimus was dominated by 0.03% tacrolimus and topical corticosteroids, and 0.03% tacrolimus produced more DCDs than topical corticosteroids but was also more costly (the cost per additional DCD with 0.03% tacrolimus relative to topical corticosteroids was £18.10). In scenario 2, where the model was run over 51 weeks, the cost per additional DCD with tacrolimus relative to topical corticosteroids was £3.30 (moderate eczema) and £16.10 (severe eczema). Overall, differences in the costs and effectiveness of tacrolimus compared with topical corticosteroids were very small and the results were sensitive to a number of cost and effectiveness variables. For adults, results from scenario 1 showed that tacrolimus dominated topical corticosteroids in those with moderate or severe atopic eczema. In scenario 2, where the model was run over 51 weeks, tacrolimus produced more DCDs compared with topical corticosteroids but was also more costly; the cost per additional DCD with tacrolimus was £6.20 (moderate eczema) and £26.80 (severe eczema). However, patients with severe atopic eczema treated with ciclosporin achieved more DCDs than did those treated with tacrolimus, although ciclosporin was more expensive (the cost per additional DCD with ciclosporin was £4.80). These patterns were reflected in further analyses excluding work days lost. The results were sensitive to a number of variables. ## Pimecrolimus The Assessment Group's base-case results showed that, compared with topical corticosteroids, first-line use of pimecrolimus cost more and conferred slightly fewer QALYs for children and adults with atopic eczema both on the body and in sensitive areas (see Section 4.2.1.1). Using pimecrolimus as a second-line rather than first-line treatment was less expensive but was still dominated by topical corticosteroids. However, the probabilistic analyses showed that these results were associated with considerable uncertainty. The Assessment Group developed subsidiary models (one for adults and one for children) to evaluate the cost effectiveness of pimecrolimus compared with emollients, with moderately potent topical corticosteroids used as a 'rescue therapy' for all patients with uncontrolled 'problem' eczema. The basic structure of these models was the same as that of the models used to compare active treatments, although no distinction was made between eczema on sensitive areas and eczema on the rest of the body. Compared with emollients alone, the ICERs for treatment with pimecrolimus were £9700 per QALY in children and £16,600 per QALY in adults. Again, the results were associated with a high degree of uncertainty. The manufacturer developed a cost–utility model comparing pimecrolimus with emollients. A Markov approach was used, based on four states of progressive severity (remission, mild, moderate and severe). The use of topical corticosteroids was permitted as a rescue therapy in patients with severe disease. The model was run for 1 year. An NHS perspective was adopted and 2003 was the base year for estimating costs. For all parts of the body, the estimated cost per additional QALY was £24,500 in children and £27,400 in adults and, for head and neck only, £4668 in children and £21,766 in adults. The results were sensitive to a number of variables. Probabilistic analyses of the model for children showed that, when £30,000 is considered to be an acceptable amount to pay for an additional QALY, the probability of pimecrolimus being most likely to be cost effective is 60%, the probability that it will dominate vehicle is 20% and the probability that the cost for an additional QALY will be greater than £100,000 is 17%. In patients with mainly head and neck atopic eczema, the probabilities were 75%, 35% and 20%, respectively. Probabilistic analyses were not presented for adults. # Consideration of the evidence The Committee reviewed the evidence available on the clinical and cost effectiveness of tacrolimus and pimecrolimus, having considered evidence on the nature of the condition and the value placed on the benefits of tacrolimus and pimecrolimus by people with atopic eczema, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources. The Committee was persuaded that tacrolimus and pimecrolimus have both been shown to be effective in treating atopic eczema when compared with vehicle. They noted, however, that vehicle is not the most appropriate comparator in the majority of cases. The Committee observed that no studies had compared 0.03% tacrolimus in children with moderate to severe disease with potent or moderately potent topical corticosteroids, but that there was evidence from two RCTs of greater effectiveness compared with mild topical corticosteroids. It also noted that the two largest RCTs in adults that compared tacrolimus and potent topical corticosteroid regimens had produced inconsistent results: 0.1% tacrolimus was statistically significantly more effective than topical corticosteroids in the larger study, whereas no statistically significant differences were reported in the smaller study, although potent topical corticosteroids were found to be more effective than 0.03% tacrolimus. The Committee concluded that the available evidence suggested that tacrolimus was similar in effectiveness to topical corticosteroids for the treatment of moderate to severe atopic eczema. The Committee noted that there is limited evidence on the effectiveness of pimecrolimus compared with topical corticosteroids. No studies had compared pimecrolimus with topical corticosteroids in children, and the results of the studies in adults favoured topical corticosteroids. Consideration was given to the results of the economic models developed by the Assessment Group and the manufacturers of tacrolimus and pimecrolimus. The Committee acknowledged that the base-case results of the Assessment Group's model were associated with very considerable uncertainty, reflecting the closeness of the utility estimates for all the strategies, coupled with the necessity of estimating a number of parameters in the model in the absence of good-quality evidence, and of the need to combine treatment and disease states in order to address the different potential uses of the new immunomodulators. The Committee concluded that, because of the significant parameter uncertainty, the base-case ICERs could not, in themselves, provide the sole basis for a decision. It was agreed, however, that similar benefits accrue to patients with atopic eczema with tacrolimus as with the use of topical corticosteroids but at a greater cost. The Committee considered that the Fujisawa economic model of tacrolimus did not provide any evidence to override its conclusion in 4.3.5. The analysis was limited in that results were expressed only in terms of DCDs rather than QALYs; and it only compared tacrolimus treatment after the use of topical corticosteroids with tacrolimus treatment before topical corticosteroids, and not with topical corticosteroids alone. On the basis of the Assessment Group's economic model of pimecrolimus, the Committee agreed that pimecrolimus was not cost effective compared with topical corticosteroids. Although the Assessment Group's model and the manufacturer's model suggested that pimecrolimus was cost effective relative to emollients alone, the Committee was not convinced that this was the most clinically appropriate comparator in the majority of cases. The Committee was concerned by the possibility that immunomodulators might increase the risk of skin malignancy in the long term – there is some evidence that tacrolimus may reduce the time to development of ultraviolet-induced tumours in experimental animals, although this was associated with much higher systemic levels of tacrolimus than would be seen in clinical use, and it is known that systemic use of tacrolimus and related drugs is associated with the development of skin cancers. For this reason, the Committee believed that topical immunomodulators should not be used without careful discussion of the potential risks and benefits with the patient. The Committee heard from the clinical experts that topical corticosteroids provide effective first-line management of atopic eczema and that, because of the higher cost of tacrolimus and pimecrolimus and their potential unknown long-term adverse effects, the experts would not recommend either of these products as first-line treatments. The Committee heard from the clinical experts that topical immunomodulators are useful in cases where continual use of potent topical corticosteroids is required and there is a serious risk of skin atrophy. The experts also agreed that topical immunomodulators are useful alternatives to systemic treatments in severe resistant atopic eczema. The Committee heard from the clinical experts that concern about long-term adverse effects, particularly the risk of skin atrophy, causes significant anxiety about the use of topical corticosteroids in people with atopic eczema. The clinical experts were in agreement, however, that anxiety around steroid use should not be an indication for treatment with topical immunomodulators, but that this anxiety should be addressed through effective patient information and education. Taking into account the evidence on the cost and effectiveness of topical immunomodulators, and the views of the clinical experts, the Committee agreed that topical immunomodulators should not be recommended for mild atopic eczema or as first-line treatments for atopic eczema of any severity. The risk of skin atrophy associated with topical corticosteroid use was relevant only to the moderate and severe end of the disease spectrum and to continual and high-dose use. The Committee, however, did recognise the need for second-line treatments in patients with moderate to severe disease that has not been controlled by topical corticosteroids, where there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy. Only tacrolimus is licensed for severe atopic eczema, and so consideration was given to the relative benefits of pimecrolimus compared with tacrolimus for the second-line treatment of moderate atopic eczema. The Committee noted the considerably weaker evidence base for pimecrolimus compared with tacrolimus in adults and agreed that pimecrolimus should not therefore be recommended for use in adults. The Committee further considered the effectiveness of pimecrolimus and tacrolimus in children for whom the only licensed tacrolimus strength is 0.03%. The Committee noted the results of the study that compared pimecrolimus and 0.03% tacrolimus in children, and was persuaded by the views of some of the clinical experts that pimecrolimus is a useful treatment option for moderate facial atopic eczema in children because of its different formulation and tolerability to tacrolimus. The Committee therefore concluded that tacrolimus should be recommended as an option for the second-line treatment of moderate to severe atopic eczema in adults and children aged 2 years and older in the circumstances outlined in Section 4.3.12. The Committee also concluded that pimecrolimus could be recommended as an option for the second-line treatment of moderate atopic eczema on the face and neck in children aged 2 to 16 years, but that it should not be recommended for use on other parts of the body. It was agreed that, for the purposes of this guidance, atopic eczema that has not been controlled by topical corticosteroids would refer to disease that has not shown a satisfactory clinical response to adequate use of the maximum strength and potency of topical corticosteroid that is appropriate for the patient's age and the area being treated. Finally, the Committee considered how and by whom tacrolimus and pimecrolimus should be prescribed. Given the uncertainties around the long-term effects of the immunomodulators, the Committee agreed that it would be appropriate to recommend that they be initiated only by physicians (including general practitioners) with a special interest and experience in dermatology, and only after careful discussion with the patient of the potential risks and benefits of all appropriate second-line treatment options.# Recommendations for further research Given that 0.03% tacrolimus in children with moderate to severe atopic eczema has only been compared with mild topical corticosteroids, the Committee recommends that high-quality studies be undertaken using moderately potent topical corticosteroids as a comparator. The Committee recommends that high-quality RCTs of pimecrolimus compared with appropriate potencies of topical corticosteroids be undertaken in children and adults with mild to moderate atopic eczema. The Committee recommends that additional head-to-head studies of tacrolimus and pimecrolimus be conducted to enable further direct comparisons of efficacy to be made. The Committee emphasises the need for careful and long-term surveillance for adverse effects of tacrolimus and pimecrolimus, including skin and other types of malignancy. To achieve greater consensus among researchers and clinicians on how to measure treatment success in studies of atopic eczema, the Committee recommends that further research be conducted into the reliability of methods of measurement. The Committee recommends that observational studies be conducted to provide basic information about the treatment patterns and health service utilisation by people with atopic eczema in England and Wales.# Implications for the NHS The guidance will affect only a small proportion of people with atopic eczema who have moderate or severe forms of the disease (see Section 2.3). It is not clear what proportion of people with moderate or severe disease currently experience an unsatisfactory clinical response to adequate use of the maximum strength and potency of topical corticosteroid that is appropriate for their age and the area being treated and who are at serious risk of developing important adverse effects from further topical corticosteroid use such as permanent skin atrophy. It is therefore unclear what proportion of people with moderate or severe atopic eczema would use tacrolimus or pimecrolimus under this guidance. For pimecrolimus, this is further complicated by the lack of information on the number of children with moderate atopic eczema that has not been controlled by topical corticosteroids and who are affected by the disease on the face and neck. The cost per gram of topical corticosteroids (3–14p) is small compared with the cost per gram of tacrolimus (62–68p) and the cost per gram of pimecrolimus (59p). By varying estimates around the cost of topical corticosteroids and the quantity used, a crude calculation suggests that the additional cost per year per patient compared with topical corticosteroids would lie between £538 and £1192 for tacrolimus and between £511 and £1117 for pimecrolimus. However, these estimates assume that all other treatment costs, such as the number of visits to physicians, the incidence of adverse effects such as infections and the quantity of the topical immunomodulators required, compared with topical corticosteroids, would remain the same. Using the above estimates, the additional spending in a Primary Care Trust (PCT) with a population of 100,000 people was calculated crudely, assuming different levels of uptake with tacrolimus and pimecrolimus. The calculations assumed the point prevalence of atopic eczema to be 13.4% (based on a prevalence study in the UK in 1996), that 14% of people with atopic eczema have moderate disease and that 2% of people with atopic eczema have severe disease. On the basis of these assumptions, the estimated additional annual spending in a PCT this size would be: between £11,500 and £25,600 if 1% of people currently using topical corticosteroids with moderate or severe disease need to switch to tacrolimus, and between £9600 and £21,000 if 1% of people with moderate disease need to switch to pimecrolimus (in this case, children with atopic eczema on the face or neck) between £23,100 and £51,100 if 2% of people currently using topical corticosteroids with moderate or severe disease need to switch to tacrolimus, and between £19,200 and £41,900 if 2% of people with moderate disease need to switch to pimecrolimus (in this case, children with atopic eczema on the face or neck) between £57,700 and £127,800 if 5% of people currently using topical corticosteroids with moderate or severe disease need to switch to tacrolimus, and between £47,900 and £104,800 if 5% of people with moderate disease need to switch to pimecrolimus (in this case, children with atopic eczema on the face or neck). Given the number of assumptions involved in the calculations, these estimates should be interpreted cautiously. In addition, it is known that 610,000 prescriptions for tacrolimus with a total net ingredient cost of £2,260,300 and 21,650 prescriptions for pimecrolimus with a total net ingredient cost of £652,900 were issued in England during 2003. It has therefore been estimated that a PCT with a population of 100,000 would have spent around £4500 on prescriptions for tacrolimus and around £1300 on prescriptions for pimecrolimus during this time.# Related guidance The frequency of application of topical corticosteroids for atopic eczema is currently being appraised by NICE and guidance is due to be published in August 2004, subject to any appeals.# Review of guidance The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review. The guidance on this technology will be reviewed in August 2007. Andrew DillonChief ExecutiveAugust 2004# Appendix C. Detail on criteria for audit of the use of tacrolimus and pimecrolimus for atopic eczema # Possible objectives for an audit An audit could be carried out to ensure that pimecrolimus and tacrolimus are prescribed appropriately. # Possible patients to be included in the audit An audit could be carried out on all children and adults seen for atopic eczema in a reasonable period for audit, for example, 6 months. # Measures that could be used as a basis for an audit The measures that could be used in an audit of the appropriateness of prescription of tacrolimus and pimecrolimus for atopic eczema are as follows. Criterion Standard Exception Definition of terms . Topical tacrolimus or pimecrolimus are prescribed for the treatment of mild atopic eczema or as first-line treatments for atopic eczema of any severity % of people with atopic eczema None The diagnosis of atopic eczema is established by the individual having an itchy skin condition in the last 12 months, plus three or more of the following criteria: history of flexural involvement (that is, affecting the bends of the elbow or behind the knees); history of a generally dry skin; personal history of other atopic disease (in children under 4 years, history of atopic disease in a first-degree relative may be included); visible flexural dermatitis as defined by a photographic protocol; and onset below the age of 2 years (not used in children under 4 years). Clinicians will need to agree locally on how to identify people with mild atopic eczema for audit purposes. . Topical tacrolimus is considered, within its licensed indications, as an option for the second-line treatment of moderate or severe atopic eczema in adults and children aged 2 years and over in the following circumstances: a. the individual's atopic eczema has not been controlled by topical corticosteroids and b. there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy % of adults and children aged 2 years and older with moderate or severe atopic eczema that has not been controlled by topical corticosteroids and where there is a serious risk of important adverse effects from further topical corticosteroid use None Clinicians will need to agree locally on how to identify people with moderate or severe atopic eczema and how to document that topical tacrolimus has been considered, within its licensed indications, as an option, for audit purposes. 'Atopic eczema that has not been controlled by topical corticosteroids' refers to disease that has not shown a satisfactory clinical response to adequate use of the maximum strength and potency that is appropriate for the patient's age and the area being treated. Clinicians will need to agree locally on what constitutes adequate use of appropriate potency topical corticosteroids, for audit purposes, but anxiety around topical corticosteroid use alone should not be considered an indication for treatment with tacrolimus. Irreversible skin atrophy includes telangiectasia, increased transparency and shininess of the skin and the appearance of striae. . Pimecrolimus is considered, within its licensed indications, as an option for the second-line treatment of moderate atopic eczema on the face or neck in children aged 2 to 16 years in the following circumstances: a. the child's facial atopic eczema has not been controlled by topical corticosteroids and b. there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy % of children aged 2 to 16 years with moderate atopic eczema on the face or neck that has not been controlled by topical corticosteroids and where there is a serious risk of important adverse effects from further topical corticosteroid use None See above for definitions. . Treatment with tacrolimus or pimecrolimus is initiated only by a physician with a special interest and experience in dermatology % of people who are prescribed tacrolimus or pimecrolimus None 'A physician with a special interest and experience in dermatology' can be a physician or a general practitioner. . Treatment with tacrolimus or pimecrolimus is initiated only after careful discussion between the prescribing physician and the patient of the potential risks and benefits of all appropriate second-line treatment options % of people who are prescribed tacrolimus or pimecrolimus None Clinicians will need to agree locally on how the discussion with the patient is documented, for audit purposes. Risks of topical tacrolimus include side effects such as a burning or tingling sensation, pruritus, erythema, folliculitis, herpes simplex, acne, increased sensitivity to hot and cold, alcohol intolerance and lymphadenopathy. Risks of pimecrolimus include side effects such as a burning sensation, pruritus, erythema, skin infections (including folliculitis, herpes simplex and zoster, impetigo and molluscum contagiosum), papilloma (rarely) and local reactions such as pain, paraesthesia, peeling, dryness, oedema and worsening of eczema. The discussion should make clear to the patient that the potential long-term adverse effects of topical tacrolimus or pimecrolimus are not yet known and that it is possible that topical immunomodulators might increase the risk of skin malignancy in the long-term. Second-line treatment options, in addition to tacrolimus and pimecrolimus, include systemic corticosteroids, phototherapy and systemic use of immunosuppressants such as ciclosporin. Clinicians will need to agree locally on the risks and benefits of second-line treatment options that are discussed with the patient, for audit purposes. # Calculation of compliance Compliance (%) with each measure described in the table above is calculated as follows. Number of patients whose care is consistent with the criterion plus number of patients who meet any exception listed x 100 Number of patients to whom the measure applies Clinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.# Changes after publication Since the NICE guidance on topical pimecrolimus and tacrolimus was issued, following a safety review the European Medicines Evaluation Agency (EMEA) has recommended greater caution in the way these medicines are used in order to reduce potential risks of skin cancer and lymphoma as far as possible. Patients who are using tacrolimus and pimecrolimus should not stop or modify their treatment without consulting their prescribing healthcare professional. Further details can be found on the EMEA website. March 2014: implementation section updated to clarify that tacrolimus and pimecrolimus are recommended as options for treating atopic eczema. Additional minor maintenance update also carried out. March 2012: minor maintenance# About this guidance NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales. We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.	{'Guidance': "Topical tacrolimus and pimecrolimus are not recommended for the treatment of mild atopic eczema or as first-line treatments for atopic eczema of any severity.\n\nTopical tacrolimus is recommended, within its licensed indications, as an option for the second-line treatment of moderate to severe atopic eczema in adults and children aged 2 years and older that has not been controlled by topical corticosteroids (see Section 1.4), where there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy.\n\nPimecrolimus is recommended, within its licensed indications, as an option for the second-line treatment of moderate atopic eczema on the face and neck in children aged 2 to 16\xa0years that has not been controlled by topical corticosteroids (see Section 1.4), where there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy.\n\nFor the purposes of this guidance, atopic eczema that has not been controlled by topical corticosteroids refers to disease that has not shown a satisfactory clinical response to adequate use of the maximum strength and potency that is appropriate for the patient's age and the area being treated.\n\nIt is recommended that treatment with tacrolimus or pimecrolimus be initiated only by physicians (including general practitioners) with a special interest and experience in dermatology, and only after careful discussion with the patient about the potential risks and benefits of all appropriate second-line treatment options.", 'Clinical need and practice': "Atopic eczema (synonymous with atopic dermatitis) is a chronic relapsing skin condition characterised by intense itching, dry skin, redness, inflammation and exudation. It affects mainly the flexor surfaces of the elbows and knees, as well as the face and neck.\n\nThe term 'atopic' refers to the association with atopy (a state of hypersensitivity to common environmental allergens that may be inherited) and differentiates atopic eczema from other forms of eczema such as irritant, allergic contact, discoid, venous, seborrhoeic and photosensitive eczema, which have different disease patterns and aetiologies.\n\nEstimates of prevalence vary but suggest that the condition may affect as many as 15–20% of school-age children and 2–10% of adults. The majority of people with atopic eczema (over 80%) experience mild disease, whereas only a small proportion (around 2–4%) have a severe form of the disease. Despite the lower prevalence, the presentation of disease in adults is often more severe and chronic in nature.\n\nIn most people with atopic eczema, the condition begins in early childhood – often in the first year of life, when it can be particularly severe. Findings from the National Child Development Study, developed from the birth cohort of 1958, suggest an incidence of around 50 cases per 1000 in the first year of life, falling to 5 new cases per 1000 per year for the rest of childhood. In around 60% of children, the condition clears by the time they reach their teens. However, the tendency towards dry and irritable skin generally persists and later recurrences are common.\n\nThe aetiology of atopic eczema is complex and not fully understood. Genetic factors are important but environmental factors, such as house dust mites, pollen, tobacco, air pollution and low humidity, may cause its onset and/or exacerbate existing symptoms. More persistent disease has been consistently linked with early disease onset, severe widespread disease in early life, concomitant asthma or hay fever, and a family history of atopic eczema. The condition is exacerbated by soap and detergents, clothes containing wool or certain synthetic fibres, and extremes of temperature.\n\nThe severity of atopic eczema varies enormously, from an occasional dry, scaly patch to a debilitating disease where much of the body is covered by excoriated (scratched and abraded), bleeding and infected lesions. Its course may be continuous for prolonged periods or of a relapsing–remitting nature characterised by acute flare-ups.\n\nItching skin (pruritus) is a major symptom of atopic eczema. A vicious circle can occur, where itching and scratching damage the skin and increase inflammation, which in turn increases the itch. Scratching can damage the skin and cause bleeding, secondary infection and thickening of the skin (lichenification).\n\nThe impact of atopic eczema on quality of life can be considerable and it has been shown to vary according to disease severity. In addition to the burden of daily treatment, studies have shown not only that the condition may affect everyday activities, such as work or school, and social relationships, but also that people with atopic eczema may experience anxiety, depression and other psychological problems. Sleep disturbance is common, especially during flare-ups, which in turn can lead to problems with irritability and lack of concentration. Severe atopic eczema in children can also have a significant impact on family life, with parents/carers having to cope with the demands associated with caring for a child with a chronic illness.\n\nHistorically, there have been variations in the clinical definition and diagnosis of atopic eczema. A UK Working Party has developed criteria for use in epidemiological studies, and these are now commonly used, although further validation is required. To qualify as a case of atopic eczema using these criteria, the person must have had an itchy skin condition in the last 12\xa0months, plus three or more of the following criteria:\n\na history of flexural involvement (that is, affecting the bends of the elbows or behind the knees)\n\na history of a generally dry skin\n\na personal history of other atopic disease (in children under 4\xa0years, a history of atopic disease in a first-degree relative may be included)\n\nvisible flexural dermatitis as defined by a photographic protocol\n\nonset at younger than age 2\xa0years (not used in children under 4\xa0years).\n\nThere is uncertainty and a lack of standardisation around clinical assessment of disease severity, both in practice and in trial settings. Although a number of scoring systems have been used to categorise the disease as mild, moderate or severe, usually by aggregating scores from a range of symptoms and disease characteristics, none of these scoring systems has been accepted as a 'gold standard' and there is still general debate over their use.\n\nAtopic eczema in childhood shows a reverse social class gradient, with higher rates in socio-economically advantaged groups and smaller families. There is also evidence of variation in prevalence by region, with the highest rates recorded in the South East and industrialised Midlands, and the lowest rates in Wales and Scotland.\n\nManagement of atopic eczema takes place predominantly in primary care, and aims to relieve symptoms and prevent complications such as infection until remission occurs. This management involves the identification and avoidance of exacerbating factors, skin care and anti-inflammatory treatment. Providing people with good-quality information about these issues is essential to successfully managing and treating atopic eczema. Referral to secondary care is only advised if the condition is severe and has not responded to appropriate therapy.\n\nEmollients form a standard part of skin care and aim to retain the skin's barrier function (keeping water in and irritants or pathogens out) and prevent painful cracking. Frequent and continuous use is recommended even in the absence of symptoms. Preparations include bath oils, soap substitutes and moisturisers.\n\nTopical corticosteroids are the first-line treatment for episodic worsening (flare-ups) of atopic eczema. In order to reduce exposure to topical corticosteroids, they are used only intermittently to control exacerbations. Emollients are used with the topical corticosteroids.\n\nTopical corticosteroids are classified according to their potency. This is determined by the amount of vasoconstriction a topical corticosteroid produces and the degree to which it inhibits inflammation (a more potent product increases suppression to the inflammatory pathway). In the UK, four potencies are recognised: mild, moderately potent, potent and very potent. Across the different potencies, products have different formulations and different strengths (for example, 0.025%, 0.1%, 0.5%) and are available in various preparations (for example, ointment, cream, lotion, foam).\n\nTreatment regimens for topical corticosteroids vary with disease severity, with clinicians usually recommending use of the mildest potency products possible to treat the condition, in order to minimise the potential adverse effects.\n\nOne of the potential long-term effects of topical corticosteroid treatment is skin atrophy, whereby the skin becomes thin and loses some of its function. This is more likely to occur in areas where the skin is already thin, such as the face and flexures. Although reversible in the short term, prolonged exposure can lead to permanent damage. Signs of atrophy include telangiectasia (abnormal dilation of capillary vessels and arterioles), increased transparency and shininess of the skin, and the appearance of striae (stripes or lines in the skin distinguished from surrounding tissue by colour, texture or elevation). Long-term use of topical corticosteroids on the eyelids has also been associated with the development of glaucoma.\n\nSystemic adverse effects with topical corticosteroids are rare but include suppression of the pituitary–adrenal axis (which may restrict growth).\n\nAbsorption of topical corticosteroids is higher at certain sites such as the face and flexures, and potent topical corticosteroids are generally avoided in these areas. The more potent topical corticosteroids are also contraindicated in infants younger than 1\xa0year and are avoided in children or used with great care and for short periods. A potent or moderately potent topical corticosteroid may be appropriate for severe atopic eczema on the limbs, but for 1–2\xa0weeks only, followed by a weaker preparation as the condition improves.\n\nIn resistant severe cases, treatment with systemic corticosteroids, phototherapy and systemic use of immunosuppressants, such as ciclosporin, may be required.", 'The technologies': 'Tacrolimus and pimecrolimus are members of a new class of topical immunomodulators and belong to the class of immunosuppressant drugs known as calcineurin inhibitors. They work mainly by reducing inflammation through the suppression of T-lymphocyte responses, a different mechanism of action to topical corticosteroids. Although tacrolimus and pimecrolimus have similar mechanisms of action, they have different licensed indications (see Sections 3.1 and 3.2).\n\n# Tacrolimus\n\nTacrolimus ointment (Fujisawa) is available in two strengths (0.1% and 0.03%), both of which are licensed for the treatment of moderate to severe atopic eczema in adults (16\xa0years and above) who have not adequately responded to, or are intolerant of, conventional therapies. The lower strength is also licensed for the treatment of moderate to severe atopic eczema in children aged 2\xa0years and older whose condition has not responded adequately to conventional therapies.\n\nThe Summary of Product Characteristics states that tacrolimus should "be prescribed by physicians with experience in the treatment of atopic dermatitis".\n\nTacrolimus is applied as a thin layer to affected areas of the skin twice daily and may be used on any part of the body, including the face, neck and flexural areas. The Summary of Product Characteristics states that the treatment of each affected region of the skin should be continued until the area is clear, and then be discontinued. It also states that treatment for adults should be started with 0.1% tacrolimus twice a day, that twice-daily treatment with 0.1% tacrolimus should be restarted if symptoms recur, and that an attempt should be made to reduce the frequency of application or to use the lower strength 0.03% tacrolimus if the clinical condition allows. For children, only the 0.03% strength is licensed, and the Summary of Product Characteristics states that the frequency of application should be reduced to once a day after a maximum of 3\xa0weeks.\n\nTacrolimus can be used for short-term and intermittent long-term treatment. The net price is £21.60 for 30\xa0g and £41.04 for 60\xa0g (0.1% tacrolimus) and £19.44 for 30\xa0g and £36.94 for 60\xa0g (0.03% tacrolimus) (British National Formulary, 46th edition). Costs may vary in different settings because of negotiated procurement discounts.\n\nSide effects include a burning or tingling sensation, pruritus, erythema, folliculitis, herpes simplex infection, acne, increased sensitivity to hot and cold, and alcohol intolerance. Lymphadenopathy has also been reported. The Summary of Product Characteristics states that before commencing treatment with tacrolimus, clinical infections at treatment sites should be cleared. It also states that emollients should not be applied to the same area within 2 hours of applying tacrolimus. When taken orally for other indications, tacrolimus has a number of well-recognised adverse effects, including renal toxicity and hypertension. The Summary of Product Characteristics states that, beyond 4\xa0years of treatment, the potential for local immunosuppression (possibly resulting in infections or cutaneous malignancies) is unknown. For full details of side effects and contraindications, see the Summary of Product Characteristics.\n\n# Pimecrolimus\n\nPimecrolimus cream 1.0% (Novartis) is licensed in patients with mild to moderate atopic eczema aged 2\xa0years and older, for short-term treatment of signs and symptoms and intermittent long-term treatment to prevent flare-ups.\n\nPimecrolimus is applied as a thin layer to affected skin twice daily and may be used on all skin areas, including the head, face, neck and intertriginous areas (where opposing skin surfaces touch and may rub, such as skin folds of the groin, axillae and breasts). The treatment of each affected region of the skin is continued until the area is clear and is then discontinued. Because of the low level of systemic absorption, there are no restrictions on the total daily dose applied, the body surface area that can be treated or the duration of treatment. The Summary of Product Characteristics states that emollients can be applied immediately after using pimecrolimus. The net price is £19.69 for 30\xa0g, £37.41 for 60\xa0g and £59.07 for 100\xa0g (British National Formulary, 46th edition). Costs may vary in different settings because of negotiated procurement discounts.\n\nSide effects include a burning sensation, pruritus, erythema, skin infections (including folliculitis and rarely impetigo, herpes simplex and zoster and molluscum contagiosum), papilloma (rarely) and local reactions such as pain, paraesthesia, peeling, dryness, oedema and worsening of eczema. The Summary of Product Characteristics states that pimecrolimus should not be applied to areas affected by acute cutaneous viral infections, and that before commencing treatment with pimecrolimus, clinical infections at treatment sites should be cleared. It also states that long-term effect on the local skin immune response and on the incidence of skin malignancies is unknown. For full details of side effects and contraindications, see the Summary of Product Characteristics.', 'Evidence and interpretation': "The Appraisal Committee (Appendix A) considered evidence from a number of sources (Appendix B).\n\n# Clinical effectiveness\n\nTen randomised controlled trials (RCTs) of tacrolimus and eight RCTs of pimecrolimus for the treatment of atopic eczema were considered. In most of the studies, comparators were topical corticosteroids or vehicle (a placebo consisting of the base cream or ointment without the active ingredient).\n\nEffectiveness was assessed in different ways across the trials, but common measures included the following:\n\nchanges in severity using the Eczema Area Severity Index (EASI) or modified Eczema Area Severity Index (mEASI), which are well established assessment tools that account for individual symptoms and disease severity in four predefined regions of the body\n\nthe Investigator's Global Assessment (IGA), a physician's rating scale based on interpretation of signs of eczema\n\nthe Physician's Global Evaluation (PGE) of treatment success, which estimates the percentage change in the condition since the person was last seen\n\nthe physician's evaluation of reduction in affected body surface area (BSA)\n\npatient-based measures such as number of flare-ups, pruritus and use of alternative treatments, such as topical corticosteroids.The main quality-of-life measure used in the trials was the Dermatology Life Quality Index (DLQI), which is a 10-item, self-administered questionnaire designed to measure the impact of skin diseases on patients' lives over the previous week.\n\n## Tacrolimus\n\nOf the ten RCTs of tacrolimus, four were conducted in children and six in adults, all in populations with moderate to severe disease, reflecting the licensed indications.\n\nTwo of the studies in children compared tacrolimus with mild topical corticosteroids (n\xa0=\xa0374 and n\xa0=\xa0417 ['n' refers to overall study size]) and two compared it with vehicle (n\xa0=\xa0180 and n\xa0=\xa0352). Results were considered for 0.03% tacrolimus only, because 0.1% tacrolimus is not licensed for use in children. No trials in children have compared tacrolimus with potent or moderately potent topical corticosteroids.\n\nThree of the RCTs in adults used potent topical corticosteroid regimens as a comparator (n\xa0=\xa0181, n\xa0=\xa0570 and n\xa0=\xa0975) and three used vehicle (n\xa0=\xa014, n\xa0=\xa0215 and n\xa0=\xa0632).\n\nFor children, a pooled analysis of two studies that compared 0.03% tacrolimus with mild topical corticosteroids showed 0.03% tacrolimus to be more effective at 3\xa0weeks, as measured by an improvement of at least 90% ('cleared' to 'excellent improvement') in the PGE (relative risk [RR] 2.56, 95% confidence interval [CI] 1.95 to 3.36). Based on the median improvement in mEASI score, both studies also showed 0.03% tacrolimus to be statistically significantly more effective than mild topical corticosteroids.\n\nBoth studies in children comparing 0.03% tacrolimus and vehicle found tacrolimus to be more effective using the PGE categories of 'cleared' to 'marked improvement' (56.5% vs 15.7% in the larger study [p\xa0<\xa00.001] and 69.0% vs 38.0% in the smaller study [p\xa0<\xa00.01] for 0.03% tacrolimus vs vehicle). Statistically significant differences were also demonstrated for a number of other measures, including changes in EASI score, pruritus score and patient reports of 'feeling better'. Loss to follow-up was higher in the vehicle arms of the trials (56.0% vs 17.0% in the larger study and 15.9% vs 8.1% in the smaller study).\n\nFor adults, a pooled analysis of two studies (n\xa0=\xa0181 and n\xa0=\xa0570) comparing 0.1% tacrolimus and potent topical corticosteroids found no statistically significant difference in the proportions of people with an improvement of at least 75% on the PGE ('cleared' to 'marked improvement') at 3\xa0weeks (RR 1.08, 95% CI 0.97 to 1.21).\n\nThe pooled analysis did not include the largest study (n\xa0=\xa0975), which compared 0.1% tacrolimus with mild topical corticosteroids on the face and with potent topical corticosteroids on the body. Overall, this study found a greater improvement on the PGE with tacrolimus (62.9% vs 40.7% at 3\xa0months, difference = 22.2%, 95% CI 16.1 to 28.4). This study reported other statistically significant differences favouring tacrolimus compared with a topical corticosteroid regimen. This included a higher proportion of people achieving an improvement in mEASI by at least 60% at 3\xa0months (the primary outcome), a greater median improvement in mEASI (83.3% vs 76.9% at 3\xa0months, p\xa0<\xa00.001; also statistically significant at 4 and 6\xa0months, 95% CIs not stated), a greater reduction in the affected BSA, and a greater proportion of people 'feeling better'. However, there was a high loss to follow-up (25.5% with tacrolimus and 42.1% with topical corticosteroids).\n\nThe other two studies that compared 0.1% tacrolimus and potent topical corticosteroids in adults did not report any statistically significant differences, although the larger of the two (n\xa0=\xa0570) found smaller improvements in median mEASI score with 0.03% tacrolimus compared with potent topical corticosteroids (71% vs 83%, p\xa0<\xa00.05). Loss to follow-up in this study was 11.5% with tacrolimus and 9.1% with topical corticosteroids.\n\nCompared with vehicle, treatment of adults with tacrolimus was shown to be statistically significantly more effective using a number of outcome measures, including the PGE categories of 'cleared' to 'marked improvement', reduction in BSA affected, and improvement in EASI score. Loss to follow-up was noticeably high in the vehicle arms of the trials (68.4% vs 26.7% and 38.9% vs 13.2% in the two largest trials).\n\nQuality of life measures were reported by one study with an active comparator (n\xa0=\xa0975) and one vehicle-controlled study in which participants were drawn from subsets of the largest studies of adults and children (n\xa0=\xa0985). Both studies measured quality of life using the DLQI. Compared with a topical corticosteroid regimen (potent topical corticosteroid on the body and mild topical corticosteroid on the face), greater percentage improvements were found with 0.1% tacrolimus (66.7% vs 58.5% at 3\xa0months and 74.3% vs 69.2% at 6\xa0months, statistical significance was not reported), although the results for the different dimensions of 'quality of life' were not reported separately. Compared with vehicle, both strengths of tacrolimus were associated with greater improvements across all measurement dimensions in adults (symptoms and feelings, daily activities, leisure, work/school, personal relations, treatment [p\xa0=\xa00.0001]). In children (using the Children's DLQI [CDLQI] completed by children with help from parents/guardians), greater improvements were found with 0.03% tacrolimus than with vehicle across all measurement dimensions except one (the personal relationships dimension [p\xa0<\xa00.0001 to p\xa0=\xa00.02]) and across all dimensions for toddlers (using the CDLQI for toddlers completed by parents/guardians [p\xa0<\xa00.0001 to p\xa0=\xa00.001]).\n\nFor adverse effects, pooled analyses showed no statistically significant differences in skin infection rates between tacrolimus and topical corticosteroids. However, there was more skin burning in children with 0.03% tacrolimus compared with mild topical corticosteroids (RR 1.97, 95% CI 1.25 to 3.11) and in adults with 0.1% tacrolimus compared with potent topical corticosteroid regimens (RR 4.17, 95% CI 3.36 to 5.18). Withdrawal because of adverse effects was similar for tacrolimus and topical corticosteroids (1.6% to 3.9% of the tacrolimus group vs 1.6% to 3.3% of those using topical corticosteroids) but was consistently higher in the vehicle arms of the trials (4.5% to 12.3% with vehicle vs 2.9% to 5.7% with tacrolimus).\n\nOverall, tacrolimus is more effective in treating moderate to severe disease in adults and children than vehicle alone. In children, a number of measures of treatment effect suggest that tacrolimus is also more effective than mild topical corticosteroids but no trials have compared it with more potent topical corticosteroids. In adults, compared with topical corticosteroids, 0.1% tacrolimus was statistically significantly more effective in one study (n\xa0=\xa0975) but not statistically significantly different in the other two studies (n\xa0=\xa0570 and n\xa0=\xa0181).\n\n## Pimecrolimus\n\nOf the eight RCTs of pimecrolimus, three were conducted in children and five in adults. Three of the studies were provided by the manufacturer as commercial in confidence (two studies in adults and one study in children).\n\nNone of the RCTs in children compared pimecrolimus with topical corticosteroids. Two studies used vehicle as a comparator (n\xa0=\xa0403 and n\xa0=\xa0713 ['n' refers to overall study size]) and one compared pimecrolimus with 0.03% tacrolimus (provided in confidence by the manufacturer [n\xa0=\xa0141]).\n\nTwo of the RCTs in adults used potent topical corticosteroids as a comparator (n\xa0=\xa0260 and n\xa0=\xa0658); the larger of these two RCTs was provided in confidence by the manufacturer. Three studies used vehicle as a comparator (n\xa0=\xa034, n\xa0=\xa0192 and n\xa0=\xa0260). A further vehicle-controlled study was provided in confidence by the manufacturer (n\xa0=\xa0200).\n\nOne of the studies in children (n\xa0=\xa0713) and one in adults (n\xa0=\xa0192) permitted the use of moderately potent topical corticosteroids to treat flare-ups in the treatment and control groups.\n\nThree of the studies in adults were conducted in people with moderate to severe disease, which does not match the licensed indication (see Section 3.2.1). They were included in the review for pragmatic reasons – firstly, on the basis of expert advice that there is considerable overlap between categories of eczema severity and, secondly, because of the limited evidence available from studies comparing pimecrolimus with an active treatment.\n\nCompared with potent topical corticosteroids, evidence from the smaller study suggests that pimecrolimus is less effective in treating moderate to severe atopic eczema. This study included four strengths of pimecrolimus (0.05%, 0.2%, 0.6% and 1.0%) but only the results for 1.0% pimecrolimus are presented, reflecting the product licence (see Section 3.2.1). Fewer people treated with pimecrolimus were judged to have 'clear' or 'almost clear' eczema at 3\xa0weeks using the IGA score (11.1% vs 50.0%, difference = 38.9%, 95% CI 21 to 56). The study also reported a smaller percentage reduction in EASI for those using pimecrolimus (47.0% vs 78.0%, statistical significance was not reported) and that fewer people treated with pimecrolimus had mild or absent pruritus (46.7% vs 81.0%, difference\xa0=\xa034.3%, 95% CI 15.5 to 53.1, p\xa0<\xa00.05). The risk of skin burning was greater with pimecrolimus (RR 5.26, 95% CI 1.97 to 14.0). However, almost a quarter of participants were lost to follow-up (23.5%).\n\nCompared with vehicle, pooled analyses of studies in children with mild to moderate disease and in adults with moderate to severe disease showed that treatment with pimecrolimus resulted in better IGA scores at 3 and 6\xa0weeks (RR 4.47, 95% CI 1.40 to 14.27 [3\xa0weeks]; RR 1.87, 95% CI 1.26 to 2.76 [6\xa0weeks]) and fewer flare-ups at 6\xa0months (RR 1.78, 95% CI 1.10 to 2.86). People using pimecrolimus were less likely to use additional treatment with topical corticosteroids (RR 1.82, 95% CI 1.51 to 2.21) and pruritus was more often absent or mild at 3 and 6\xa0weeks among the pimecrolimus group (RR at 3 weeks 1.99, 95% CI 1.53 to 2.58).\n\nResults from individual studies showed that pimecrolimus was statistically significantly more effective than vehicle using other measures of treatment effect, such as changes in EASI score and reduction in BSA affected.\n\nQuality of life for people treated with pimecrolimus was reported by one comparison with vehicle in adults (n\xa0=\xa0192) and for a subset of participants from the smaller study in children (n\xa0=\xa0241). The study in adults reported changes in two quality of life measures (the Quality of Life Index – Atopic Dermatitis [QoLIAD] and the DLQI) and found greater improvements among patients using pimecrolimus compared with those using vehicle for both measures (25.6% vs 7.4%, p\xa0=\xa00.002 and 22% vs 6.7%, p\xa0=\xa00.01). The study in children, which used the Parent's Index of QOL in Atopic Dermatitis, also reported a higher quality of life with pimecrolimus (p\xa0=\xa00.023).\n\nFor adverse effects, a pooled analysis showed no statistically significant differences in rates of bacterial infection and skin burning between pimecrolimus and vehicle, but there was a greater risk of viral skin infection with pimecrolimus (12% vs 6%, RR 1.97, 95% CI 1.21 to 3.19).\n\nOverall, studies found pimecrolimus to be more effective at treating atopic eczema in adults and children than was vehicle alone. There is limited evidence on the effectiveness of pimecrolimus compared with topical corticosteroids.\n\n# Cost effectiveness\n\nThe Committee considered economic analyses submitted by the manufacturers of both products and a model developed by the Assessment Group. There was only one relevant published economic analysis and this was conducted from the perspective of the US healthcare system and had methodological problems that limited its value. The Assessment Group analysis consisted of eight separate models, each relating to different cohorts of people with atopic eczema.\n\n## Tacrolimus\n\nFor the analysis of cost effectiveness in children, the Assessment Group model was run over 14\xa0years to incorporate the possibility of disease resolution. All patients were assumed to be aged 2\xa0years on entering. The model estimated that the costs per additional quality-adjusted life year (QALY) of first- and second-line treatment of eczema on the body were £9100 and £14,200, respectively, relative to the standard practice of using topical corticosteroids alone. For eczema in sensitive areas (on the face or in areas such as the armpits or groin where the treatment options are more limited because of concerns about skin atrophy), the costs per additional QALY were higher. First-line treatment cost £35,700 per additional QALY and second-line treatment was dominated by topical corticosteroids (that is, tacrolimus was both less effective and more costly than topical corticosteroids).\n\nIn adults, the cost per additional QALY of first-line treatment of eczema on the body with tacrolimus was £37,400 relative to standard treatment with topical corticosteroids. Second-line treatment of 'body' eczema with tacrolimus cost less than topical corticosteroids alone but also conferred fewer QALYs. For eczema in sensitive areas (see Section 4.2.1.1), the cost per additional QALY of first-line treatment with tacrolimus was £11,900, and second-line treatment with tacrolimus was dominated by topical corticosteroids.\n\nUsing a lower estimate of the amount of tacrolimus ointment used (2.3\xa0g per day rather than 6.8\xa0g per day) for adults reduced the incremental cost effectiveness ratio (ICER) for the treatment of 'body' eczema with tacrolimus (first-line) to £30,300 per QALY. Second-line treatment of 'body' eczema with tacrolimus still cost less than topical corticosteroids alone whilst also conferring fewer QALYs. The ICER for first-line treatment of eczema in sensitive areas (see Section 4.2.1.1) was also lower (£7000 per QALY), but tacrolimus as a second-line treatment continued to be dominated by topical corticosteroids.\n\nOverall, tacrolimus (first- and second-line) was estimated to be more costly than topical corticosteroids alone in all cases except one (second-line treatment of 'body' eczema in adults), whilst absolute differences in QALYs were very small. The Assessment Group also performed probabilistic analyses. The base-case results of all the Assessment Group's models were shown to be associated with considerable uncertainty, due mainly to the very small incremental benefits predicted.\n\nThe manufacturer provided a cost-effectiveness analysis, in terms of disease-controlled days (DCDs), and compared treatment with tacrolimus (0.1% in adults, and 0.1% and 0.03% in children) after topical corticosteroids (potent topical corticosteroids as comparator for 0.1% tacrolimus, mild topical corticosteroids as comparator for 0.03% tacrolimus) with treatment with tacrolimus before topical corticosteroids in a hospital outpatient setting. The model adopted a semi-Markov approach, organised in four arms (topical corticosteroids in moderate or severe disease and tacrolimus in moderate or severe disease), and each one included four states of progression of atopic eczema (cleared or virtually cleared, moderately controlled, uncontrolled and flare-up). Each arm was run for 27\xa0weeks (adults) or 15\xa0weeks (children), corresponding to the duration of follow-up in the RCTs from which the effectiveness estimates were derived (scenario 1). In a second scenario, the model was run for 51\xa0weeks on the basis of effectiveness estimates obtained from experts, and ciclosporin was included as a comparator for adults with severe eczema. A modified NHS and Personal and Social Services perspective was adopted, including work days lost.\n\nThe results were presented as average cost-effectiveness ratios rather than ICERs. The Assessment Group calculated ICERs using the data provided by the manufacturer.\n\nFor children with moderate disease, results from scenario 1 showed that 0.03% tacrolimus was dominated by both topical corticosteroids and 0.1% tacrolimus (that is, it produced fewer DCDs and was more costly than topical corticosteroids and 0.1% tacrolimus) and that 0.1% tacrolimus produced more DCDs than topical corticosteroids but was also more costly (the cost per additional DCD with 0.1% tacrolimus relative to topical corticosteroids was £16.40). In contrast, for children with severe disease, 0.1% tacrolimus was dominated by 0.03% tacrolimus and topical corticosteroids, and 0.03% tacrolimus produced more DCDs than topical corticosteroids but was also more costly (the cost per additional DCD with 0.03% tacrolimus relative to topical corticosteroids was £18.10). In scenario 2, where the model was run over 51\xa0weeks, the cost per additional DCD with tacrolimus relative to topical corticosteroids was £3.30 (moderate eczema) and £16.10 (severe eczema). Overall, differences in the costs and effectiveness of tacrolimus compared with topical corticosteroids were very small and the results were sensitive to a number of cost and effectiveness variables.\n\nFor adults, results from scenario 1 showed that tacrolimus dominated topical corticosteroids in those with moderate or severe atopic eczema. In scenario 2, where the model was run over 51\xa0weeks, tacrolimus produced more DCDs compared with topical corticosteroids but was also more costly; the cost per additional DCD with tacrolimus was £6.20 (moderate eczema) and £26.80 (severe eczema). However, patients with severe atopic eczema treated with ciclosporin achieved more DCDs than did those treated with tacrolimus, although ciclosporin was more expensive (the cost per additional DCD with ciclosporin was £4.80). These patterns were reflected in further analyses excluding work days lost. The results were sensitive to a number of variables.\n\n## Pimecrolimus\n\nThe Assessment Group's base-case results showed that, compared with topical corticosteroids, first-line use of pimecrolimus cost more and conferred slightly fewer QALYs for children and adults with atopic eczema both on the body and in sensitive areas (see Section 4.2.1.1). Using pimecrolimus as a second-line rather than first-line treatment was less expensive but was still dominated by topical corticosteroids. However, the probabilistic analyses showed that these results were associated with considerable uncertainty.\n\nThe Assessment Group developed subsidiary models (one for adults and one for children) to evaluate the cost effectiveness of pimecrolimus compared with emollients, with moderately potent topical corticosteroids used as a 'rescue therapy' for all patients with uncontrolled 'problem' eczema. The basic structure of these models was the same as that of the models used to compare active treatments, although no distinction was made between eczema on sensitive areas and eczema on the rest of the body. Compared with emollients alone, the ICERs for treatment with pimecrolimus were £9700 per QALY in children and £16,600 per QALY in adults. Again, the results were associated with a high degree of uncertainty.\n\nThe manufacturer developed a cost–utility model comparing pimecrolimus with emollients. A Markov approach was used, based on four states of progressive severity (remission, mild, moderate and severe). The use of topical corticosteroids was permitted as a rescue therapy in patients with severe disease. The model was run for 1\xa0year. An NHS perspective was adopted and 2003 was the base year for estimating costs.\n\nFor all parts of the body, the estimated cost per additional QALY was £24,500 in children and £27,400 in adults and, for head and neck only, £4668 in children and £21,766 in adults. The results were sensitive to a number of variables. Probabilistic analyses of the model for children showed that, when £30,000 is considered to be an acceptable amount to pay for an additional QALY, the probability of pimecrolimus being most likely to be cost effective is 60%, the probability that it will dominate vehicle is 20% and the probability that the cost for an additional QALY will be greater than £100,000 is 17%. In patients with mainly head and neck atopic eczema, the probabilities were 75%, 35% and 20%, respectively. Probabilistic analyses were not presented for adults.\n\n# Consideration of the evidence\n\nThe Committee reviewed the evidence available on the clinical and cost effectiveness of tacrolimus and pimecrolimus, having considered evidence on the nature of the condition and the value placed on the benefits of tacrolimus and pimecrolimus by people with atopic eczema, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources.\n\nThe Committee was persuaded that tacrolimus and pimecrolimus have both been shown to be effective in treating atopic eczema when compared with vehicle. They noted, however, that vehicle is not the most appropriate comparator in the majority of cases.\n\nThe Committee observed that no studies had compared 0.03% tacrolimus in children with moderate to severe disease with potent or moderately potent topical corticosteroids, but that there was evidence from two RCTs of greater effectiveness compared with mild topical corticosteroids. It also noted that the two largest RCTs in adults that compared tacrolimus and potent topical corticosteroid regimens had produced inconsistent results: 0.1% tacrolimus was statistically significantly more effective than topical corticosteroids in the larger study, whereas no statistically significant differences were reported in the smaller study, although potent topical corticosteroids were found to be more effective than 0.03% tacrolimus. The Committee concluded that the available evidence suggested that tacrolimus was similar in effectiveness to topical corticosteroids for the treatment of moderate to severe atopic eczema.\n\nThe Committee noted that there is limited evidence on the effectiveness of pimecrolimus compared with topical corticosteroids. No studies had compared pimecrolimus with topical corticosteroids in children, and the results of the studies in adults favoured topical corticosteroids.\n\nConsideration was given to the results of the economic models developed by the Assessment Group and the manufacturers of tacrolimus and pimecrolimus. The Committee acknowledged that the base-case results of the Assessment Group's model were associated with very considerable uncertainty, reflecting the closeness of the utility estimates for all the strategies, coupled with the necessity of estimating a number of parameters in the model in the absence of good-quality evidence, and of the need to combine treatment and disease states in order to address the different potential uses of the new immunomodulators. The Committee concluded that, because of the significant parameter uncertainty, the base-case ICERs could not, in themselves, provide the sole basis for a decision. It was agreed, however, that similar benefits accrue to patients with atopic eczema with tacrolimus as with the use of topical corticosteroids but at a greater cost.\n\nThe Committee considered that the Fujisawa economic model of tacrolimus did not provide any evidence to override its conclusion in 4.3.5. The analysis was limited in that results were expressed only in terms of DCDs rather than QALYs; and it only compared tacrolimus treatment after the use of topical corticosteroids with tacrolimus treatment before topical corticosteroids, and not with topical corticosteroids alone.\n\nOn the basis of the Assessment Group's economic model of pimecrolimus, the Committee agreed that pimecrolimus was not cost effective compared with topical corticosteroids. Although the Assessment Group's model and the manufacturer's model suggested that pimecrolimus was cost effective relative to emollients alone, the Committee was not convinced that this was the most clinically appropriate comparator in the majority of cases.\n\nThe Committee was concerned by the possibility that immunomodulators might increase the risk of skin malignancy in the long term – there is some evidence that tacrolimus may reduce the time to development of ultraviolet-induced tumours in experimental animals, although this was associated with much higher systemic levels of tacrolimus than would be seen in clinical use, and it is known that systemic use of tacrolimus and related drugs is associated with the development of skin cancers. For this reason, the Committee believed that topical immunomodulators should not be used without careful discussion of the potential risks and benefits with the patient.\n\nThe Committee heard from the clinical experts that topical corticosteroids provide effective first-line management of atopic eczema and that, because of the higher cost of tacrolimus and pimecrolimus and their potential unknown long-term adverse effects, the experts would not recommend either of these products as first-line treatments.\n\nThe Committee heard from the clinical experts that topical immunomodulators are useful in cases where continual use of potent topical corticosteroids is required and there is a serious risk of skin atrophy. The experts also agreed that topical immunomodulators are useful alternatives to systemic treatments in severe resistant atopic eczema.\n\nThe Committee heard from the clinical experts that concern about long-term adverse effects, particularly the risk of skin atrophy, causes significant anxiety about the use of topical corticosteroids in people with atopic eczema. The clinical experts were in agreement, however, that anxiety around steroid use should not be an indication for treatment with topical immunomodulators, but that this anxiety should be addressed through effective patient information and education.\n\nTaking into account the evidence on the cost and effectiveness of topical immunomodulators, and the views of the clinical experts, the Committee agreed that topical immunomodulators should not be recommended for mild atopic eczema or as first-line treatments for atopic eczema of any severity. The risk of skin atrophy associated with topical corticosteroid use was relevant only to the moderate and severe end of the disease spectrum and to continual and high-dose use. The Committee, however, did recognise the need for second-line treatments in patients with moderate to severe disease that has not been controlled by topical corticosteroids, where there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy.\n\nOnly tacrolimus is licensed for severe atopic eczema, and so consideration was given to the relative benefits of pimecrolimus compared with tacrolimus for the second-line treatment of moderate atopic eczema. The Committee noted the considerably weaker evidence base for pimecrolimus compared with tacrolimus in adults and agreed that pimecrolimus should not therefore be recommended for use in adults.\n\nThe Committee further considered the effectiveness of pimecrolimus and tacrolimus in children for whom the only licensed tacrolimus strength is 0.03%. The Committee noted the results of the study that compared pimecrolimus and 0.03% tacrolimus in children, and was persuaded by the views of some of the clinical experts that pimecrolimus is a useful treatment option for moderate facial atopic eczema in children because of its different formulation and tolerability to tacrolimus.\n\nThe Committee therefore concluded that tacrolimus should be recommended as an option for the second-line treatment of moderate to severe atopic eczema in adults and children aged 2 years and older in the circumstances outlined in Section 4.3.12. The Committee also concluded that pimecrolimus could be recommended as an option for the second-line treatment of moderate atopic eczema on the face and neck in children aged 2 to 16\xa0years, but that it should not be recommended for use on other parts of the body.\n\nIt was agreed that, for the purposes of this guidance, atopic eczema that has not been controlled by topical corticosteroids would refer to disease that has not shown a satisfactory clinical response to adequate use of the maximum strength and potency of topical corticosteroid that is appropriate for the patient's age and the area being treated.\n\nFinally, the Committee considered how and by whom tacrolimus and pimecrolimus should be prescribed. Given the uncertainties around the long-term effects of the immunomodulators, the Committee agreed that it would be appropriate to recommend that they be initiated only by physicians (including general practitioners) with a special interest and experience in dermatology, and only after careful discussion with the patient of the potential risks and benefits of all appropriate second-line treatment options.", 'Recommendations for further research': 'Given that 0.03% tacrolimus in children with moderate to severe atopic eczema has only been compared with mild topical corticosteroids, the Committee recommends that high-quality studies be undertaken using moderately potent topical corticosteroids as a comparator.\n\nThe Committee recommends that high-quality RCTs of pimecrolimus compared with appropriate potencies of topical corticosteroids be undertaken in children and adults with mild to moderate atopic eczema.\n\nThe Committee recommends that additional head-to-head studies of tacrolimus and pimecrolimus be conducted to enable further direct comparisons of efficacy to be made.\n\nThe Committee emphasises the need for careful and long-term surveillance for adverse effects of tacrolimus and pimecrolimus, including skin and other types of malignancy.\n\nTo achieve greater consensus among researchers and clinicians on how to measure treatment success in studies of atopic eczema, the Committee recommends that further research be conducted into the reliability of methods of measurement.\n\nThe Committee recommends that observational studies be conducted to provide basic information about the treatment patterns and health service utilisation by people with atopic eczema in England and Wales.', 'Implications for the NHS': 'The guidance will affect only a small proportion of people with atopic eczema who have moderate or severe forms of the disease (see Section 2.3). It is not clear what proportion of people with moderate or severe disease currently experience an unsatisfactory clinical response to adequate use of the maximum strength and potency of topical corticosteroid that is appropriate for their age and the area being treated and who are at serious risk of developing important adverse effects from further topical corticosteroid use such as permanent skin atrophy. It is therefore unclear what proportion of people with moderate or severe atopic eczema would use tacrolimus or pimecrolimus under this guidance. For pimecrolimus, this is further complicated by the lack of information on the number of children with moderate atopic eczema that has not been controlled by topical corticosteroids and who are affected by the disease on the face and neck.\n\nThe cost per gram of topical corticosteroids (3–14p) is small compared with the cost per gram of tacrolimus (62–68p) and the cost per gram of pimecrolimus (59p). By varying estimates around the cost of topical corticosteroids and the quantity used, a crude calculation suggests that the additional cost per year per patient compared with topical corticosteroids would lie between £538 and £1192 for tacrolimus and between £511 and £1117 for pimecrolimus. However, these estimates assume that all other treatment costs, such as the number of visits to physicians, the incidence of adverse effects such as infections and the quantity of the topical immunomodulators required, compared with topical corticosteroids, would remain the same.\n\nUsing the above estimates, the additional spending in a Primary Care Trust (PCT) with a population of 100,000 people was calculated crudely, assuming different levels of uptake with tacrolimus and pimecrolimus. The calculations assumed the point prevalence of atopic eczema to be 13.4% (based on a prevalence study in the UK in 1996), that 14% of people with atopic eczema have moderate disease and that 2% of people with atopic eczema have severe disease. On the basis of these assumptions, the estimated additional annual spending in a PCT this size would be:\n\nbetween £11,500 and £25,600 if 1% of people currently using topical corticosteroids with moderate or severe disease need to switch to tacrolimus, and between £9600 and £21,000 if 1% of people with moderate disease need to switch to pimecrolimus (in this case, children with atopic eczema on the face or neck)\n\nbetween £23,100 and £51,100 if 2% of people currently using topical corticosteroids with moderate or severe disease need to switch to tacrolimus, and between £19,200 and £41,900 if 2% of people with moderate disease need to switch to pimecrolimus (in this case, children with atopic eczema on the face or neck)\n\nbetween £57,700 and £127,800 if 5% of people currently using topical corticosteroids with moderate or severe disease need to switch to tacrolimus, and between £47,900 and £104,800 if 5% of people with moderate disease need to switch to pimecrolimus (in this case, children with atopic eczema on the face or neck). Given the number of assumptions involved in the calculations, these estimates should be interpreted cautiously. In addition, it is known that 610,000 prescriptions for tacrolimus with a total net ingredient cost of £2,260,300 and 21,650 prescriptions for pimecrolimus with a total net ingredient cost of £652,900 were issued in England during 2003. It has therefore been estimated that a PCT with a population of 100,000 would have spent around £4500 on prescriptions for tacrolimus and around £1300 on prescriptions for pimecrolimus during this time.', 'Related guidance': 'The frequency of application of topical corticosteroids for atopic eczema is currently being appraised by NICE and guidance is due to be published in August 2004, subject to any appeals.', 'Review of guidance': 'The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review.\n\nThe guidance on this technology will be reviewed in August 2007.\n\nAndrew DillonChief ExecutiveAugust 2004', 'Appendix C. Detail on criteria for audit of the use of tacrolimus and pimecrolimus for atopic eczema': "# Possible objectives for an audit\n\nAn audit could be carried out to ensure that pimecrolimus and tacrolimus are prescribed appropriately.\n\n# Possible patients to be included in the audit\n\nAn audit could be carried out on all children and adults seen for atopic eczema in a reasonable period for audit, for example, 6 months.\n\n# Measures that could be used as a basis for an audit\n\nThe measures that could be used in an audit of the appropriateness of prescription of tacrolimus and pimecrolimus for atopic eczema are as follows.\n\nCriterion\n\nStandard\n\nException\n\nDefinition of terms\n\n. Topical tacrolimus or pimecrolimus are prescribed for the treatment of mild atopic eczema or as first-line treatments for atopic eczema of any severity\n\n% of people with atopic eczema\n\nNone\n\nThe diagnosis of atopic eczema is established by the individual having an itchy skin condition in the last 12\xa0months, plus three or more of the following criteria: history of flexural involvement (that is, affecting the bends of the elbow or behind the knees); history of a generally dry skin; personal history of other atopic disease (in children under 4\xa0years, history of atopic disease in a first-degree relative may be included); visible flexural dermatitis as defined by a photographic protocol; and onset below the age of 2\xa0years (not used in children under 4\xa0years).\n\nClinicians will need to agree locally on how to identify people with mild atopic eczema for audit purposes.\n\n. Topical tacrolimus is considered, within its licensed indications, as an option for the second-line treatment of moderate or severe atopic eczema in adults and children aged 2\xa0years and over in the following circumstances:\n\n\n\na. the individual's atopic eczema has not been controlled by topical corticosteroids and\n\n\n\nb. there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy\n\n\n\n% of adults and children aged 2\xa0years and older with moderate or severe atopic eczema that has not been controlled by topical corticosteroids and where there is a serious risk of important adverse effects from further topical corticosteroid use\n\nNone\n\nClinicians will need to agree locally on how to identify people with moderate or severe atopic eczema and how to document that topical tacrolimus has been considered, within its licensed indications, as an option, for audit purposes.\n\n'Atopic eczema that has not been controlled by topical corticosteroids' refers to disease that has not shown a satisfactory clinical response to adequate use of the maximum strength and potency that is appropriate for the patient's age and the area being treated. Clinicians will need to agree locally on what constitutes adequate use of appropriate potency topical corticosteroids, for audit purposes, but anxiety around topical corticosteroid use alone should not be considered an indication for treatment with tacrolimus.\n\nIrreversible skin atrophy includes telangiectasia, increased transparency and shininess of the skin and the appearance of striae.\n\n. Pimecrolimus is considered, within its licensed indications, as an option for the second-line treatment of moderate atopic eczema on the face or neck in children aged 2 to 16\xa0years in the following circumstances:\n\na. the child's facial atopic eczema has not been controlled by topical corticosteroids and\n\nb. there is a serious risk of important adverse effects from further topical corticosteroid use, particularly irreversible skin atrophy\n\n% of children aged 2 to 16\xa0years with moderate atopic eczema on the face or neck that has not been controlled by topical corticosteroids and where there is a serious risk of important adverse effects from further topical corticosteroid use\n\nNone\n\nSee above for definitions.\n\n. Treatment with tacrolimus or pimecrolimus is initiated only by a physician with a special interest and experience in dermatology\n\n% of people who are prescribed tacrolimus or pimecrolimus\n\nNone\n\n'A physician with a special interest and experience in dermatology' can be a physician or a general practitioner.\n\n. Treatment with tacrolimus or pimecrolimus is initiated only after careful discussion between the prescribing physician and the patient of the potential risks and benefits of all appropriate second-line treatment options\n\n% of people who are prescribed tacrolimus or pimecrolimus\n\nNone\n\nClinicians will need to agree locally on how the discussion with the patient is documented, for audit purposes.\n\nRisks of topical tacrolimus include side effects such as a burning or tingling sensation, pruritus, erythema, folliculitis, herpes simplex, acne, increased sensitivity to hot and cold, alcohol intolerance and lymphadenopathy. Risks of pimecrolimus include side effects such as a burning sensation, pruritus, erythema, skin infections (including folliculitis, herpes simplex and zoster, impetigo and molluscum contagiosum), papilloma (rarely) and local reactions such as pain, paraesthesia, peeling, dryness, oedema and worsening of eczema.\n\nThe discussion should make clear to the patient that the potential long-term adverse effects of topical tacrolimus or pimecrolimus are not yet known and that it is possible that topical immunomodulators might increase the risk of skin malignancy in the long-term. Second-line treatment options, in addition to tacrolimus and pimecrolimus, include systemic corticosteroids, phototherapy and systemic use of immunosuppressants such as ciclosporin. Clinicians will need to agree locally on the risks and benefits of second-line treatment options that are discussed with the patient, for audit purposes.\n\n\n\n# Calculation of compliance\n\nCompliance (%) with each measure described in the table above is calculated as follows.\n\nNumber of patients whose care is consistent with the criterion plus number of patients who meet any exception listed\n\n\n\nx 100\n\nNumber of patients to whom the measure applies\n\nClinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved.", 'Changes after publication': 'Since the NICE guidance on topical pimecrolimus and tacrolimus was issued, following a safety review the European Medicines Evaluation Agency (EMEA) has recommended greater caution in the way these medicines are used in order to reduce potential risks of skin cancer and lymphoma as far as possible.\n\nPatients who are using tacrolimus and pimecrolimus should not stop or modify their treatment without consulting their prescribing healthcare professional.\n\nFurther details can be found on the EMEA website.\n\nMarch 2014: implementation section updated to clarify that tacrolimus and pimecrolimus are recommended as options for treating atopic eczema. Additional minor maintenance update also carried out.\n\nMarch 2012: minor maintenance', 'About this guidance': 'NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales.\n\nWe have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.'}	https://www.nice.org.uk/guidance/ta82	Evidence-based recommendations on tacrolimus (Protopic) and pimecrolimus (Elidel) for people with atopic eczema.
938fd17c7507289f2e1f314f92ae693e8b7077d0	nice	Photodynamic therapy for advanced bronchial carcinoma	Photodynamic therapy for advanced bronchial carcinoma # Guidance Current evidence on the safety and efficacy of photodynamic therapy for advanced bronchial carcinoma appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. These recommendations apply only to the use of this technique to treat advanced bronchial carcinoma. The Institute will consider photodynamic therapy for early bronchial carcinoma separately.# The procedure # Indications and current treatments This procedure is used to treat patients with inoperable non-small cell lung cancer, which has a poor prognosis. Alternative treatments include debulking with biopsy forceps, radiotherapy and laser resection. # Outline of the procedure Photodynamic therapy (PDT) for advanced bronchial carcinoma is a minimally invasive treatment, usually involving intravenous injection of a photosensitising agent, followed a few days later by photoradiation of the affected area through a bronchoscope. This is intended to reduce the bulk of the tumour, therefore reducing symptoms caused, for example, by bronchial obstruction. # Efficacy Three small randomised controlled trials (RCTs) were identified, in addition to nonrandomised comparative studies and case series. The two largest randomised studies compared PDT with laser treatment; both studies reported that symptomatic improvement was similar for both treatments. One of these studies reported a mean increase in forced vital capacity of 0.47 litres in the PDT group, compared with a mean decrease of 0.06 litres in the laser group (p < 0.05); and a mean increase in forced expiratory volume in 1 second of 0.35 litres for the PDT group, compared with 0.01 litres for the laser group (p < 0.05). The other study reported median time to treatment failure to be 50 days for the PDT group and 38 days for the laser group, and average survival to be 265 days for the PDT group compared with 95 days for the laser group. For more details, refer to the Sources of evidence section. The Specialist Advisors noted that it was not clear whether tumour bulk reduction in a palliative setting was associated with gains in quality of life or survival. They also noted that careful patient selection is needed. # Safety The largest RCT reported at least one adverse effect in 100% (14/14) of patients in the PDT group and 71% (12/17) of patients in the laser group. In this study, the most common adverse effects in the PDT group were bronchitis (29%, 4/14); photosensitisation (29%, 4/14); dyspnoea (21%, 3/14); and death (probably related to treatment; 7%, 1/14). For more details, refer to the Sources of evidence section. The Specialist Advisors generally considered this procedure to be safe. They listed the main potential adverse events as skin photosensitivity, bleeding, necrosis/obstruction, late strictures, oesophago–bronchial fistula formation, and airway occlusion by exudates. # Other comments The evidence for this procedure is based on small but good-quality RCTs. Further research or audits would be useful, including clinical and quality of life data. It was noted that the role of this procedure in conjunction with other techniques is uncertain.# Further information The Institute has issued guidance on chemotherapy drugs for lung cancer, and is currently developing a guideline for the diagnosis and treatment of lung cancer . For further information, visit our website. Andrew DillonChief ExecutiveAugust 2004 # Information for patients The Institute has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of photodynamic therapy for advanced bronchial carcinoma', March 2003.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of photodynamic therapy for advanced bronchial carcinoma appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThese recommendations apply only to the use of this technique to treat advanced bronchial carcinoma. The Institute will consider photodynamic therapy for early bronchial carcinoma separately.', 'The procedure': '# Indications and current treatments\n\nThis procedure is used to treat patients with inoperable non-small cell lung cancer, which has a poor prognosis.\n\nAlternative treatments include debulking with biopsy forceps, radiotherapy and laser resection.\n\n# Outline of the procedure\n\nPhotodynamic therapy (PDT) for advanced bronchial carcinoma is a minimally invasive treatment, usually involving intravenous injection of a photosensitising agent, followed a few days later by photoradiation of the affected area through a bronchoscope. This is intended to reduce the bulk of the tumour, therefore reducing symptoms caused, for example, by bronchial obstruction.\n\n# Efficacy\n\nThree small randomised controlled trials (RCTs) were identified, in addition to nonrandomised comparative studies and case series. The two largest randomised studies compared PDT with laser treatment; both studies reported that symptomatic improvement was similar for both treatments. One of these studies reported a mean increase in forced vital capacity of 0.47 litres in the PDT group, compared with a mean decrease of 0.06 litres in the laser group (p < 0.05); and a mean increase in forced expiratory volume in 1 second of 0.35 litres for the PDT group, compared with 0.01 litres for the laser group (p < 0.05). The other study reported median time to treatment failure to be 50 days for the PDT group and 38 days for the laser group, and average survival to be 265 days for the PDT group compared with 95 days for the laser group. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors noted that it was not clear whether tumour bulk reduction in a palliative setting was associated with gains in quality of life or survival. They also noted that careful patient selection is needed.\n\n# Safety\n\nThe largest RCT reported at least one adverse effect in 100% (14/14) of patients in the PDT group and 71% (12/17) of patients in the laser group. In this study, the most common adverse effects in the PDT group were bronchitis (29%, 4/14); photosensitisation (29%, 4/14); dyspnoea (21%, 3/14); and death (probably related to treatment; 7%, 1/14). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors generally considered this procedure to be safe. They listed the main potential adverse events as skin photosensitivity, bleeding, necrosis/obstruction, late strictures, oesophago–bronchial fistula formation, and airway occlusion by exudates.\n\n# Other comments\n\nThe evidence for this procedure is based on small but good-quality RCTs. Further research or audits would be useful, including clinical and quality of life data.\n\nIt was noted that the role of this procedure in conjunction with other techniques is uncertain.', 'Further information': "The Institute has issued guidance on chemotherapy drugs for lung cancer, and is currently developing a guideline for the diagnosis and treatment of lung cancer [Now published as 'The diagnosis and treatment of lung cancer']. For further information, visit our website.\n\nAndrew DillonChief ExecutiveAugust 2004\n\n# Information for patients\n\nThe Institute has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of photodynamic therapy for advanced bronchial carcinoma', March 2003.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg87
154a94ea61f48e633a61c6c76014f16cb67dc9f1	nice	Balloon valvuloplasty for aortic valve stenosis in adults and children	Balloon valvuloplasty for aortic valve stenosis in adults and children # Guidance Current evidence on the safety and efficacy of balloon valvuloplasty for aortic valve stenosis in adults and children appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. In adults, the procedure should only be used to treat patients who are unsuitable for surgery, as the efficacy is usually shortlived. In infants and children, the procedure should be undertaken in specialist paediatric cardiology units. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients into this database.# The procedure # Indications Balloon valvuloplasty is used to treat aortic valve stenosis (narrowing). This condition may be congenital, or it may develop later in life as a result of rheumatic fever or calcium build-up on the valve that occurs in some people as part of the aging process. The narrowing of the aortic valve causes the pressure in the left ventricle to increase. In order to continue to pump blood through this narrowed area, the left ventricle must pump harder, causing hypertrophy of the left ventricular muscle. Symptoms include angina, shortness of breath or fainting on exertion, and palpitations. Aortic valve stenosis may eventually lead to heart failure. In infants and children, critical aortic stenosis is very rare and balloon valvuloplasty is usually used palliatively until the child is old enough to have valve replacement. Standard treatment involves open chest surgery to perform a valvotomy or to replace the valve. # Outline of the procedure Balloon valvuloplasty involves inserting a catheter into a large blood vessel, and passing it into the narrowed aortic valve under radiological guidance. A balloon is then inflated to dilate the aortic valve orifice. This can prevent the need for open chest surgery. # Efficacy The evidence was limited to non-randomised controlled studies and case series studies. One of the studies that looked at 110 neonates found the mean reduction in systolic gradient to be 65% for the balloon valvuloplasty group, compared with 41% for the open surgery group. A study of adults older than 75 years found the mean gradient decrease to be 24 mmHg for the balloon valvuloplasty group, and 55 mmHg for the open surgery group. In another study, in which 80% (539/674) of patients were considered inappropriate for valve replacement because of age or disease, the mean pressure gradient was reduced by 26 mmHg, but follow-up was only reported for 5 weeks. For more details, refer to the Sources of evidence section. The Specialist Advisors noted that in adults, surgery was generally the first choice of procedure, but balloon valvuloplasty was useful when surgery was contraindicated. # Safety The comparative study of neonates found aortic regurgitation rates of 18% (15/82) in the balloon valvuloplasty group, compared with 3% (1/28) in the open surgery group. In this study, immediate major complications were reported in 4% (3/82) of the balloon valvuloplasty group and 0% (0/28) of the open surgery group. However, the two groups differed in their baseline characteristics. The comparative study of patients older than 75 years showed the death rate in the postoperative and follow-up periods to be 59% (27/46) in the balloon valvuloplasty group and 22% (5/23) in the open surgery group. However, the mean follow-up intervals differed between the groups (22 months for balloon valvuloplasty and 28 months for surgery). For more details, refer to the Sources of evidence section. The Specialist Advisors considered the main potential adverse effects of the procedure to be myocardial infarction, stroke, aortic valve disruption or regurgitation, myocardial rupture or perforation, mitral valve damage, arterial damage or occlusion, and arrhythmia. Andrew DillonChief ExecutiveJuly 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of balloon valvuloplasty for aortic valve stenosis', March 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication May 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of balloon valvuloplasty for aortic valve stenosis in adults and children appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nIn adults, the procedure should only be used to treat patients who are unsuitable for surgery, as the efficacy is usually shortlived.\n\nIn infants and children, the procedure should be undertaken in specialist paediatric cardiology units.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients into this database.', 'The procedure': '# Indications\n\nBalloon valvuloplasty is used to treat aortic valve stenosis (narrowing). This condition may be congenital, or it may develop later in life as a result of rheumatic fever or calcium build-up on the valve that occurs in some people as part of the aging process. The narrowing of the aortic valve causes the pressure in the left ventricle to increase. In order to continue to pump blood through this narrowed area, the left ventricle must pump harder, causing hypertrophy of the left ventricular muscle. Symptoms include angina, shortness of breath or fainting on exertion, and palpitations. Aortic valve stenosis may eventually lead to heart failure.\n\nIn infants and children, critical aortic stenosis is very rare and balloon valvuloplasty is usually used palliatively until the child is old enough to have valve replacement.\n\nStandard treatment involves open chest surgery to perform a valvotomy or to replace the valve.\n\n# Outline of the procedure\n\nBalloon valvuloplasty involves inserting a catheter into a large blood vessel, and passing it into the narrowed aortic valve under radiological guidance. A balloon is then inflated to dilate the aortic valve orifice. This can prevent the need for open chest surgery.\n\n# Efficacy\n\nThe evidence was limited to non-randomised controlled studies and case series studies. One of the studies that looked at 110 neonates found the mean reduction in systolic gradient to be 65% for the balloon valvuloplasty group, compared with 41% for the open surgery group. A study of adults older than 75 years found the mean gradient decrease to be 24 mmHg for the balloon valvuloplasty group, and 55 mmHg for the open surgery group. In another study, in which 80% (539/674) of patients were considered inappropriate for valve replacement because of age or disease, the mean pressure gradient was reduced by 26 mmHg, but follow-up was only reported for 5 weeks. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors noted that in adults, surgery was generally the first choice of procedure, but balloon valvuloplasty was useful when surgery was contraindicated.\n\n# Safety\n\nThe comparative study of neonates found aortic regurgitation rates of 18% (15/82) in the balloon valvuloplasty group, compared with 3% (1/28) in the open surgery group. In this study, immediate major complications were reported in 4% (3/82) of the balloon valvuloplasty group and 0% (0/28) of the open surgery group. However, the two groups differed in their baseline characteristics. The comparative study of patients older than 75 years showed the death rate in the postoperative and follow-up periods to be 59% (27/46) in the balloon valvuloplasty group and 22% (5/23) in the open surgery group. However, the mean follow-up intervals differed between the groups (22 months for balloon valvuloplasty and 28 months for surgery). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered the main potential adverse effects of the procedure to be myocardial infarction, stroke, aortic valve disruption or regurgitation, myocardial rupture or perforation, mitral valve damage, arterial damage or occlusion, and arrhythmia.\n\nAndrew DillonChief ExecutiveJuly 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of balloon valvuloplasty for aortic valve stenosis', March 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nMay 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg78
2ef32e382b7952b7f048565a2606191fc143916e	nice	Stent placement for vena caval obstruction	Stent placement for vena caval obstruction # Guidance Current evidence on the safety and efficacy of stent placement for vena caval obstruction appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.# The procedure # Indications Vena caval obstruction is narrowing or occlusion of the caval veins (the inferior vena cava or the superior vena cava), which return blood from the body to the heart. It is most commonly caused by cancer, especially lung cancer. Patients with malignant vena caval obstruction are very ill and have a short life expectancy. Standard treatments for malignant caval obstruction include radiotherapy and chemotherapy. These can cause severe adverse events and response to treatment may take several weeks. Stent placement can replace or supplement these treatments. # Outline of the procedure Stent placement for vena caval obstruction is a minimally invasive procedure that involves inserting a catheter into a large vein, usually in the groin, and passing it into the narrowed area under radiological guidance. A stent, which may be self-expanding or balloon-dilated, is then positioned across the narrowed area to relieve the obstruction. # Efficacy A systematic review on the treatment of superior vena caval obstruction in lung cancer identified 23 non-randomised studies (159 patients) examining the use of stents. The review reported 95% (151/159) relief from obstruction and although recurrence occurred in 11% (17/159) of patients during follow-up (up to 8 months), long-term patency was achieved in 92% (146/159). This compared with a complete relief rate of 77% (377/487) for patients treated with any combination of chemotherapy and/or radiotherapy. Median survival ranged from 1.5 to 6.5 months in the 13 studies that reported survival outcomes. For more details, refer to the Sources of evidence section. The evidence showed that the response to treatment was more rapid for patients receiving stents than for patients receiving radiotherapy or chemotherapy. One study with historical controls reported relief of obstruction immediately or within 48 hours in patients receiving stents, compared with no change before 2 weeks in patients receiving radiotherapy. For more details, refer to the Sources of evidence section. The Specialist Advisors considered stenting to be highly effective. The only concern they raised was the possible inappropriate use of stents in some young patients with a mediastinal mass on chest X-ray that may disappear quickly with chemotherapy. # Safety Few adverse events were reported. In the largest study reporting complications: 3% (2/76 patients) had misplaced stents; 1% (1/76) required anticoagulation; 1% (1/76) experienced transient chest pain; and 1% (1/76) required blood transfusion. Adverse events in another study included stent obstruction, 12% (6/52), and stent migration, 2% (1/52). For more details, refer to the Sources of evidence section. The Specialist Advisors had few concerns about the safety of this procedure. They considered the main potential adverse events to be perforation or rupture of the vena cava, migration of the stent, and embolisation. # Other comments Most evidence relates to superior vena caval obstruction in adults with carcinoma of the lung. It was noted that there was less evidence in children, and that the procedure would normally be undertaken in specialist paediatric cardiology units. Andrew DillonChief ExecutiveJuly 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of stent placement for vena caval obstruction', April 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of stent placement for vena caval obstruction appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.', 'The procedure': '# Indications\n\nVena caval obstruction is narrowing or occlusion of the caval veins (the inferior vena cava or the superior vena cava), which return blood from the body to the heart. It is most commonly caused by cancer, especially lung cancer. Patients with malignant vena caval obstruction are very ill and have a short life expectancy.\n\nStandard treatments for malignant caval obstruction include radiotherapy and chemotherapy. These can cause severe adverse events and response to treatment may take several weeks. Stent placement can replace or supplement these treatments.\n\n# Outline of the procedure\n\nStent placement for vena caval obstruction is a minimally invasive procedure that involves inserting a catheter into a large vein, usually in the groin, and passing it into the narrowed area under radiological guidance. A stent, which may be self-expanding or balloon-dilated, is then positioned across the narrowed area to relieve the obstruction.\n\n# Efficacy\n\nA systematic review on the treatment of superior vena caval obstruction in lung cancer identified 23 non-randomised studies (159 patients) examining the use of stents. The review reported 95% (151/159) relief from obstruction and although recurrence occurred in 11% (17/159) of patients during follow-up (up to 8 months), long-term patency was achieved in 92% (146/159). This compared with a complete relief rate of 77% (377/487) for patients treated with any combination of chemotherapy and/or radiotherapy. Median survival ranged from 1.5 to 6.5 months in the 13 studies that reported survival outcomes. For more details, refer to the Sources of evidence section.\n\nThe evidence showed that the response to treatment was more rapid for patients receiving stents than for patients receiving radiotherapy or chemotherapy. One study with historical controls reported relief of obstruction immediately or within 48 hours in patients receiving stents, compared with no change before 2 weeks in patients receiving radiotherapy. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered stenting to be highly effective. The only concern they raised was the possible inappropriate use of stents in some young patients with a mediastinal mass on chest X-ray that may disappear quickly with chemotherapy.\n\n# Safety\n\nFew adverse events were reported. In the largest study reporting complications: 3% (2/76 patients) had misplaced stents; 1% (1/76) required anticoagulation; 1% (1/76) experienced transient chest pain; and 1% (1/76) required blood transfusion. Adverse events in another study included stent obstruction, 12% (6/52), and stent migration, 2% (1/52). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors had few concerns about the safety of this procedure. They considered the main potential adverse events to be perforation or rupture of the vena cava, migration of the stent, and embolisation.\n\n# Other comments\n\nMost evidence relates to superior vena caval obstruction in adults with carcinoma of the lung.\n\nIt was noted that there was less evidence in children, and that the procedure would normally be undertaken in specialist paediatric cardiology units.\n\nAndrew DillonChief ExecutiveJuly 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of stent placement for vena caval obstruction', April 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg79
a010056a036718b549e574dca071909b358f4627	nice	Fallopian tube recanalisation by guidewire	Fallopian tube recanalisation by guidewire # Guidance Fallopian tube recanalisation by guidewire is safe enough for use, provided that the normal arrangements are in place for consent, audit and clinical governance. The efficacy of the procedure in improving the chance of pregnancy is impossible to gauge from available research. Clinicians wishing to undertake fallopian tube recanalisation by guidewire should take the following actions: Ensure that patients understand the uncertainty about the procedure's efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes including pregnancy rates of all patients having fallopian tube recanalisation by guidewire.# The procedure # Indications Fallopian tube recanalisation by guidewire is a treatment for infertility caused by blocked fallopian tubes, especially if the blockage is close to the entrance to the uterus (proximal). Alternative radiological methods of clearing tubal obstruction include balloon tuboplasty, which involves inflating a small balloon within the fallopian tube. Tubal obstruction may also be treated surgically. # Outline of the procedure Fallopian tube recanalisation by guidewire is carried out during the same treatment session as diagnostic salpingography and involves inserting a catheter into the fallopian tube. This, or the subsequent injection of radio-opaque dye, may clear the obstruction. If these strategies fail, a guidewire may be passed up into the fallopian tube through the catheter, and manipulated to clear the obstruction. # Efficacy No controlled studies were identified. In one study, successful recanalisation was reported in 77% (321/417) of the tubes of 302 patients. Thirty (10%) of these 302 patients became pregnant without further infertility treatment within 12 months of undergoing the procedure. In another study, successful recanalisation was reported in 75% (176/234) of patients. Of these, 22% (39/176) had subsequent live births. For more details, refer to the Sources of evidence section. One Specialist Advisor noted that the degree of efficacy may depend on patient selection. # Safety In the studies identified, the rate of tubal perforation ranged from 1% (4/417) to 11% (4/38), and the rate of tubal pregnancy from 0.4% (1/234) to 8% (3/38). Other reported complications were sepsis in 0.9% (2/234) of patients, and pain requiring medication in 3% (7/234 and 4/150) of patients. For more details, refer to the Sources of evidence section. The Specialist Advisors listed the main potential complications as fallopian tube perforation, intra-abdominal bleeding and infection. # Other comments There is a distinction between efficacy in terms of opening the fallopian tubes and in terms of achieving pregnancy. The procedure is often used as an adjunct to other fertility treatments. There is a potential risk of tubal perforation that may then reduce the chance of pregnancy. Although the evidence showed an increased risk of tubal pregnancy, it was noted that there was generally a greater risk of tubal pregnancy in patients with tubal disease, even without this procedure.# Further information The Institute has issued a clinical guideline, 'Fertility: assessment and treatment for people with fertility problems'. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of fallopian tube recanalisation by guidewire', May 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Fallopian tube recanalisation by guidewire is safe enough for use, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe efficacy of the procedure in improving the chance of pregnancy is impossible to gauge from available research.\n\nClinicians wishing to undertake fallopian tube recanalisation by guidewire should take the following actions:\n\nEnsure that patients understand the uncertainty about the procedure's efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes including pregnancy rates of all patients having fallopian tube recanalisation by guidewire.", 'The procedure': '# Indications\n\nFallopian tube recanalisation by guidewire is a treatment for infertility caused by blocked fallopian tubes, especially if the blockage is close to the entrance to the uterus (proximal).\n\nAlternative radiological methods of clearing tubal obstruction include balloon tuboplasty, which involves inflating a small balloon within the fallopian tube. Tubal obstruction may also be treated surgically.\n\n# Outline of the procedure\n\nFallopian tube recanalisation by guidewire is carried out during the same treatment session as diagnostic salpingography and involves inserting a catheter into the fallopian tube. This, or the subsequent injection of radio-opaque dye, may clear the obstruction. If these strategies fail, a guidewire may be passed up into the fallopian tube through the catheter, and manipulated to clear the obstruction.\n\n# Efficacy\n\nNo controlled studies were identified. In one study, successful recanalisation was reported in 77% (321/417) of the tubes of 302 patients. Thirty (10%) of these 302 patients became pregnant without further infertility treatment within 12 months of undergoing the procedure. In another study, successful recanalisation was reported in 75% (176/234) of patients. Of these, 22% (39/176) had subsequent live births. For more details, refer to the Sources of evidence section.\n\nOne Specialist Advisor noted that the degree of efficacy may depend on patient selection.\n\n# Safety\n\nIn the studies identified, the rate of tubal perforation ranged from 1% (4/417) to 11% (4/38), and the rate of tubal pregnancy from 0.4% (1/234) to 8% (3/38). Other reported complications were sepsis in 0.9% (2/234) of patients, and pain requiring medication in 3% (7/234 and 4/150) of patients. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors listed the main potential complications as fallopian tube perforation, intra-abdominal bleeding and infection.\n\n# Other comments\n\nThere is a distinction between efficacy in terms of opening the fallopian tubes and in terms of achieving pregnancy.\n\nThe procedure is often used as an adjunct to other fertility treatments.\n\nThere is a potential risk of tubal perforation that may then reduce the chance of pregnancy.\n\nAlthough the evidence showed an increased risk of tubal pregnancy, it was noted that there was generally a greater risk of tubal pregnancy in patients with tubal disease, even without this procedure.', 'Further information': "The Institute has issued a clinical guideline, 'Fertility: assessment and treatment for people with fertility problems'.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of fallopian tube recanalisation by guidewire', May 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg71
77f8314a967b1f28ba67ee981c0515272f6c42d4	nice	Balloon angioplasty of pulmonary vein stenosis in infants	Balloon angioplasty of pulmonary vein stenosis in infants # Guidance Current evidence on the safety and efficacy of balloon angioplasty of pulmonary vein stenosis in infants does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. The available evidence suggests that the procedure is not efficacious. However, there are no special concerns about the safety of the procedure, especially in the context of very ill infants for whom it is used. Clinicians wishing to undertake balloon angioplasty of pulmonary vein stenosis in infants should take the following actions: Inform the clinical governance leads in their Trusts. Ensure that the parents of patients understand that the limited available evidence indicates a lack of efficacy. Parents should be given clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having balloon angioplasty of pulmonary vein stenosis in infancy. This procedure should only be offered to gravely ill infants with a very poor prognosis, and in the setting of a specialist paediatric cardiology unit. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Pulmonary vein stenosis (narrowing) may be congenital or may be acquired after surgery to correct other congenital cardiac anomalies. It is rare and often associated with other cardiac abnormalities. Untreated, it leads to severe lung damage. There is currently no reliable alternative treatment. # Outline of the procedure Balloon angioplasty of pulmonary vein stenosis, sometimes combined with stenting, is a palliative treatment for children with a very poor prognosis, or is sometimes a temporary measure for children awaiting further interventions. The procedure involves inserting a catheter into the narrowed area under radiological guidance. A balloon is then inflated to relieve the narrowing. A stent may be inserted after dilatation to maintain patency. # Efficacy The evidence was limited to four very small, poor-quality case series, the largest including only five patients. The two largest studies found no benefit from the procedure in any patients. Another study of three patients found an immediate reduction in pulmonary vein pressure in all the patients, as well as angiographic evidence of relief of stenosis in one patient. However, this patient died of infection within 36 hours of surgery. For more details, refer to the Sources of evidence section. The Specialist Advisors considered that this procedure may have only short-term efficacy (if any at all), and that recurrence rates may be high. They also noted, however, that there was almost no role for surgery in this condition, and that even a partial result from this procedure may offer palliation in this group of patients. # Safety Some of the main adverse events reported in the studies included: venous tear leading to mediastinal haemorrhage in 20% (1/5) of patients; haemoptysis in 20% (1/5) of patients; death caused by infection in 33% (1/3) of patients; and puncture of the distal vein in 33% (1/3) of patients. For more details, refer to the Sources of evidence section. The Specialist Advisors considered the main potential adverse events to be death, rupture of myocardium, rupture of pulmonary vein, cerebral or other systemic embolism, arrhythmias and sepsis. Andrew DillonChief ExecutiveJuly 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of balloon angioplasty of pulmonary vein stenosis in infants', March 2003. # Information for patients NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication As part of the NICE's work programme, the current guidance was considered for review but did not meet the review criteria as set out in the IP process guide. This guidance therefore remains current. May 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of balloon angioplasty of pulmonary vein stenosis in infants does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. The available evidence suggests that the procedure is not efficacious. However, there are no special concerns about the safety of the procedure, especially in the context of very ill infants for whom it is used.\n\nClinicians wishing to undertake balloon angioplasty of pulmonary vein stenosis in infants should take the following actions:\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that the parents of patients understand that the limited available evidence indicates a lack of efficacy. Parents should be given clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having balloon angioplasty of pulmonary vein stenosis in infancy.\n\nThis procedure should only be offered to gravely ill infants with a very poor prognosis, and in the setting of a specialist paediatric cardiology unit.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients onto this database.\n\nPublication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.", 'The procedure': '# Indications\n\nPulmonary vein stenosis (narrowing) may be congenital or may be acquired after surgery to correct other congenital cardiac anomalies. It is rare and often associated with other cardiac abnormalities. Untreated, it leads to severe lung damage.\n\nThere is currently no reliable alternative treatment.\n\n# Outline of the procedure\n\nBalloon angioplasty of pulmonary vein stenosis, sometimes combined with stenting, is a palliative treatment for children with a very poor prognosis, or is sometimes a temporary measure for children awaiting further interventions. The procedure involves inserting a catheter into the narrowed area under radiological guidance. A balloon is then inflated to relieve the narrowing. A stent may be inserted after dilatation to maintain patency.\n\n# Efficacy\n\nThe evidence was limited to four very small, poor-quality case series, the largest including only five patients. The two largest studies found no benefit from the procedure in any patients. Another study of three patients found an immediate reduction in pulmonary vein pressure in all the patients, as well as angiographic evidence of relief of stenosis in one patient. However, this patient died of infection within 36 hours of surgery. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered that this procedure may have only short-term efficacy (if any at all), and that recurrence rates may be high. They also noted, however, that there was almost no role for surgery in this condition, and that even a partial result from this procedure may offer palliation in this group of patients.\n\n# Safety\n\nSome of the main adverse events reported in the studies included: venous tear leading to mediastinal haemorrhage in 20% (1/5) of patients; haemoptysis in 20% (1/5) of patients; death caused by infection in 33% (1/3) of patients; and puncture of the distal vein in 33% (1/3) of patients. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered the main potential adverse events to be death, rupture of myocardium, rupture of pulmonary vein, cerebral or other systemic embolism, arrhythmias and sepsis.\n\nAndrew DillonChief ExecutiveJuly 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of balloon angioplasty of pulmonary vein stenosis in infants', March 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': "As part of the NICE's work programme, the current guidance was considered for review but did not meet the review criteria as set out in the IP process guide. This guidance therefore remains current.\n\nMay 2012: minor maintenance.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg75
5d41f5ecea6d853b00b1c80551230ecabd70afd8	nice	Balloon dilatation with or without stenting for pulmonary artery or non-valvar right ventricular outflow tract obstruction in children	Balloon dilatation with or without stenting for pulmonary artery or non-valvar right ventricular outflow tract obstruction in children # Guidance Current evidence on the safety and efficacy of balloon dilatation with or without stenting for pulmonary artery or non-valvar right ventricular outflow tract obstruction in children appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. The procedure should only be undertaken in specialist paediatric cardiology units. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients into this database.# The procedure # Indications The right ventricular outflow tract includes the pulmonary valve and the tissue above and below it. Narrowing (stenosis) of this region may involve the area below the valve (subvalvar), the valve itself (valvar), or the area above the valve (supravalvar). Balloon dilatation of valvar right ventricular outflow tract narrowing (pulmonary valve stenosis) is covered in separate guidance. Congenital subvalvar and supravalvar right ventricular outflow tract stenosis usually occurs with other cardiac defects, such as ventricular septal defect or tetralogy of Fallot. Postoperative right ventricular outflow tract obstruction may occur after surgery to create a conduit between the right ventricle and pulmonary artery in children with congenital anomalies. Narrowing may also occur beyond the right ventricular outflow tract, in one of the pulmonary arteries, or in their branches. Standard treatment of non-valvar right ventricular outflow tract or pulmonary artery obstruction involves open chest surgery. # Outline of the procedure Balloon dilatation is a minimally invasive procedure that involves inserting a catheter into a large blood vessel, usually in the groin, and passing it up to the area of narrowing under radiological guidance. A balloon is then inflated within the narrowing to dilate the obstruction. Stenting involves the insertion of a small tube into the narrow region following balloon dilatation, to maintain patency. # Efficacy No comparative studies were identified. Reports of technical success rates (defined as > 50% increase in pre-dilatation diameter, > 50% decrease in pressure gradient or > 20% decrease in right ventricular to aortic peak pressure ratio) were 97% (77/79) for stent insertion and 60% (97/162) for balloon dilatation in one study, and 53% (39/74) for balloon dilatation in another study. For more details, refer to the Sources of evidence section. The Specialist Advisors had no concerns regarding the efficacy of this procedure. # Safety One of the studies reported a 3% (5/162) complication rate for patients undergoing balloon dilatation. This included one femoral vein thrombosis, three pulmonary artery major dissections, and one transient pulmonary oedema. One study of stent implantation reported a complication rate of 1% (1/79 – a pleural perforation with haemopericardium). For more details, refer to the Sources of evidence section. The Specialist Advisors listed potential complications as arrhythmia, haemorrhage, stent migration, embolisation, balloon rupture, blood vessel damage and tricuspid valve damage. # Other comments Fewer data were available on the use of the technique for non-valvar right ventricular outflow tract obstruction than for pulmonary artery or branch pulmonary artery obstruction. Andrew DillonChief ExecutiveJuly 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of balloon dilation with or without stenting for pulmonary artery or right ventricular outflow tract obstruction', April 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication May 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of balloon dilatation with or without stenting for pulmonary artery or non-valvar right ventricular outflow tract obstruction in children appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe procedure should only be undertaken in specialist paediatric cardiology units.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients into this database.', 'The procedure': '# Indications\n\nThe right ventricular outflow tract includes the pulmonary valve and the tissue above and below it. Narrowing (stenosis) of this region may involve the area below the valve (subvalvar), the valve itself (valvar), or the area above the valve (supravalvar). Balloon dilatation of valvar right ventricular outflow tract narrowing (pulmonary valve stenosis) is covered in separate guidance.\n\nCongenital subvalvar and supravalvar right ventricular outflow tract stenosis usually occurs with other cardiac defects, such as ventricular septal defect or tetralogy of Fallot. Postoperative right ventricular outflow tract obstruction may occur after surgery to create a conduit between the right ventricle and pulmonary artery in children with congenital anomalies. Narrowing may also occur beyond the right ventricular outflow tract, in one of the pulmonary arteries, or in their branches.\n\nStandard treatment of non-valvar right ventricular outflow tract or pulmonary artery obstruction involves open chest surgery.\n\n# Outline of the procedure\n\nBalloon dilatation is a minimally invasive procedure that involves inserting a catheter into a large blood vessel, usually in the groin, and passing it up to the area of narrowing under radiological guidance. A balloon is then inflated within the narrowing to dilate the obstruction. Stenting involves the insertion of a small tube into the narrow region following balloon dilatation, to maintain patency.\n\n# Efficacy\n\nNo comparative studies were identified. Reports of technical success rates (defined as > 50% increase in pre-dilatation diameter, > 50% decrease in pressure gradient or > 20% decrease in right ventricular to aortic peak pressure ratio) were 97% (77/79) for stent insertion and 60% (97/162) for balloon dilatation in one study, and 53% (39/74) for balloon dilatation in another study. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors had no concerns regarding the efficacy of this procedure.\n\n# Safety\n\nOne of the studies reported a 3% (5/162) complication rate for patients undergoing balloon dilatation. This included one femoral vein thrombosis, three pulmonary artery major dissections, and one transient pulmonary oedema. One study of stent implantation reported a complication rate of 1% (1/79 – a pleural perforation with haemopericardium). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors listed potential complications as arrhythmia, haemorrhage, stent migration, embolisation, balloon rupture, blood vessel damage and tricuspid valve damage.\n\n# Other comments\n\nFewer data were available on the use of the technique for non-valvar right ventricular outflow tract obstruction than for pulmonary artery or branch pulmonary artery obstruction.\n\nAndrew DillonChief ExecutiveJuly 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of balloon dilation with or without stenting for pulmonary artery or right ventricular outflow tract obstruction', April 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nMay 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg76
580bf20fa9770f89c85940b26b4eb55cd0c17c67	nice	Balloon dilatation of systemic to pulmonary arterial shunts in children	Balloon dilatation of systemic to pulmonary arterial shunts in children # Guidance Current evidence on the safety and efficacy of balloon dilatation of systemic to pulmonary arterial shunts in children appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. The procedure should only be undertaken in specialist paediatric cardiology units. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients into this database.# The procedure # Indications Systemic to pulmonary arterial shunts are surgically created connections between the aorta and a pulmonary artery in children with cyanotic congenital heart disease, such as tetralogy of Fallot or tricuspid atresia. The shunts increase the blood supply to the lungs and the arterial oxygen saturation. The procedures are palliative. In some children, definitive surgery may be possible later. The most common type of systemic to pulmonary shunt is known as the Blalock–Taussig shunt. Systemic to pulmonary shunts may become blocked or narrowed (stenosed) because of scarring or thrombosis. Stenosed systemic to pulmonary shunts may be treated by a repeat surgical systemic to pulmonary shunt operation. # Outline of the procedure Balloon dilatation of systemic to pulmonary shunts is a palliative procedure carried out to relieve blockage or narrowing of pulmonary shunts. The procedure involves inserting a catheter into a large blood vessel (usually in the groin), passing it up into the chest under radiological guidance and inflating a balloon in the narrowed area. This may avoid the need for a repeat surgical systemic to pulmonary shunt procedure. # Efficacy The evidence was limited to small uncontrolled case series. All these studies reported increases in mean oxygen saturation, ranging from 5% to 19%. One of the studies reported successful dilatation (> 20% increase in oxygen saturation) in 91% (42/46) of patients. For more details, refer to the Sources of evidence section. The Specialist Advisors had no concerns regarding the efficacy of this procedure. # Safety Adverse events were poorly reported in the largest study, which included 46 people. The main adverse events reported in the next largest studies included: one patient with pulmonary hypertension and one death because of pneumonia (could not be weaned off ventilator) in a study of eight patients; and one patient with a thrombosed femoral artery, one patient with balloon rupture and one case of severe arterial vasospasm in a study of six patients. For more details, refer to the Sources of evidence section. Potential adverse events noted by the Specialist Advisors included tearing of the vessel or shunt, death, complete shunt occlusion, rupture, thrombosis, haemorrhage, embolic stroke, and pulmonary embolism. Andrew DillonChief ExecutiveJuly 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of balloon dilatation of systemic to pulmonary arterial shunts', April 2003. # Information for patients NICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication May 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of balloon dilatation of systemic to pulmonary arterial shunts in children appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe procedure should only be undertaken in specialist paediatric cardiology units.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients into this database.', 'The procedure': '# Indications\n\nSystemic to pulmonary arterial shunts are surgically created connections between the aorta and a pulmonary artery in children with cyanotic congenital heart disease, such as tetralogy of Fallot or tricuspid atresia. The shunts increase the blood supply to the lungs and the arterial oxygen saturation. The procedures are palliative. In some children, definitive surgery may be possible later. The most common type of systemic to pulmonary shunt is known as the Blalock–Taussig shunt.\n\nSystemic to pulmonary shunts may become blocked or narrowed (stenosed) because of scarring or thrombosis. Stenosed systemic to pulmonary shunts may be treated by a repeat surgical systemic to pulmonary shunt operation.\n\n# Outline of the procedure\n\nBalloon dilatation of systemic to pulmonary shunts is a palliative procedure carried out to relieve blockage or narrowing of pulmonary shunts. The procedure involves inserting a catheter into a large blood vessel (usually in the groin), passing it up into the chest under radiological guidance and inflating a balloon in the narrowed area. This may avoid the need for a repeat surgical systemic to pulmonary shunt procedure.\n\n# Efficacy\n\nThe evidence was limited to small uncontrolled case series. All these studies reported increases in mean oxygen saturation, ranging from 5% to 19%. One of the studies reported successful dilatation (> 20% increase in oxygen saturation) in 91% (42/46) of patients. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors had no concerns regarding the efficacy of this procedure.\n\n# Safety\n\nAdverse events were poorly reported in the largest study, which included 46 people. The main adverse events reported in the next largest studies included: one patient with pulmonary hypertension and one death because of pneumonia (could not be weaned off ventilator) in a study of eight patients; and one patient with a thrombosed femoral artery, one patient with balloon rupture and one case of severe arterial vasospasm in a study of six patients. For more details, refer to the Sources of evidence section.\n\nPotential adverse events noted by the Specialist Advisors included tearing of the vessel or shunt, death, complete shunt occlusion, rupture, thrombosis, haemorrhage, embolic stroke, and pulmonary embolism.\n\nAndrew DillonChief ExecutiveJuly 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of balloon dilatation of systemic to pulmonary arterial shunts', April 2003.\n\n# Information for patients\n\nNICE has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nMay 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg77
2ba9ed537e2b16d0eb7bf303d29d335f64314936	nice	Scleral expansion surgery for presbyopia	Scleral expansion surgery for presbyopia # Guidance Current evidence on the safety and efficacy of scleral expansion surgery for presbyopia is very limited. There is no evidence of efficacy in the majority of patients. There are also concerns about the potential risks of the procedure. It is recommended that this procedure should not be used. The Institute's information for the public complements this guidance in explaining the concerns about the procedure.# The procedure # Indications Presbyopia is an age-related and progressive loss of focusing power of the lens in the eye. It leads to a gradual decline in the ability to focus on close objects. Standard treatment for presbyopia is the use of corrective spectacles. As the condition worsens, prescriptions need to be changed accordingly. # Outline of the procedure Scleral expansion surgery involves making small incisions in the eye and inserting bands to stretch the part of the sclera that lies beneath the ciliary muscles that control accommodation. This procedure is claimed to improve accommodation. # Efficacy All studies identified were of poor quality. The evidence was limited to one non-randomised controlled study of 29 patients, two very small case series (of six and three patients, respectively) and two case reports. In the controlled study, in which the dominant eye was operated on and the other eye served as a control, improvement in median reading acuity score at 20 cm was reported as –0.41 for operated eyes and –0.35 for control eyes (p < 0.03), indicating that the improvement in operated eyes was greater. No significant difference in reading acuity was found at 30 cm or 40 cm. One case series reported that near visual acuity improved temporarily in 3/8 eyes (38%), but it was no better than before surgery at day 360. In the same study, implanted bands were removed from three eyes upon patient request because of lack of benefit. In another case series of three patients, scleral expansion surgery failed to restore accommodation in any patients. For more details, refer to the Sources of evidence section. The Specialist Advisors considered the evidence to suggest that the procedure is not efficacious. One Advisor noted that the procedure was controversial because it was based on a novel theory of the mechanism of accommodation of the human eye that was in direct opposition to other generally accepted theories. # Safety The complications reported in the identified studies were: two case reports of band removal because of band migration or chronic pain and swelling; two cases of perforated conjunctiva in a study of 8 patients; and one report of transient elevation of intraocular pressure in a study of 29 patients. For more details, refer to the Sources of evidence section. The Specialist Advisors listed the main potential adverse events as intraocular haemorrhage, retinal detachment, endophthalmitis, glaucoma, conjunctival scarring and scleral thinning. Andrew DillonChief ExecutiveJuly 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of sclera expansion surgery for presbyopia', April 2003. # Information for the public NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of scleral expansion surgery for presbyopia is very limited. There is no evidence of efficacy in the majority of patients. There are also concerns about the potential risks of the procedure.\n\nIt is recommended that this procedure should not be used. The Institute's information for the public complements this guidance in explaining the concerns about the procedure.", 'The procedure': '# Indications\n\nPresbyopia is an age-related and progressive loss of focusing power of the lens in the eye. It leads to a gradual decline in the ability to focus on close objects.\n\nStandard treatment for presbyopia is the use of corrective spectacles. As the condition worsens, prescriptions need to be changed accordingly.\n\n# Outline of the procedure\n\nScleral expansion surgery involves making small incisions in the eye and inserting bands to stretch the part of the sclera that lies beneath the ciliary muscles that control accommodation. This procedure is claimed to improve accommodation.\n\n# Efficacy\n\nAll studies identified were of poor quality. The evidence was limited to one non-randomised controlled study of 29 patients, two very small case series (of six and three patients, respectively) and two case reports. In the controlled study, in which the dominant eye was operated on and the other eye served as a control, improvement in median reading acuity score at 20 cm was reported as –0.41 for operated eyes and –0.35 for control eyes (p < 0.03), indicating that the improvement in operated eyes was greater. No significant difference in reading acuity was found at 30 cm or 40 cm. One case series reported that near visual acuity improved temporarily in 3/8 eyes (38%), but it was no better than before surgery at day 360. In the same study, implanted bands were removed from three eyes upon patient request because of lack of benefit. In another case series of three patients, scleral expansion surgery failed to restore accommodation in any patients. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered the evidence to suggest that the procedure is not efficacious. One Advisor noted that the procedure was controversial because it was based on a novel theory of the mechanism of accommodation of the human eye that was in direct opposition to other generally accepted theories.\n\n# Safety\n\nThe complications reported in the identified studies were: two case reports of band removal because of band migration or chronic pain and swelling; two cases of perforated conjunctiva in a study of 8 patients; and one report of transient elevation of intraocular pressure in a study of 29 patients. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors listed the main potential adverse events as intraocular haemorrhage, retinal detachment, endophthalmitis, glaucoma, conjunctival scarring and scleral thinning.\n\nAndrew DillonChief ExecutiveJuly 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of sclera expansion surgery for presbyopia', April 2003.\n\n# Information for the public\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg70
d85407b2454f32774f80847a1ceae76ca14c3ea0	nice	Balloon angioplasty with or without stenting for coarctation or recoarctation of the aorta in adults and children	Balloon angioplasty with or without stenting for coarctation or recoarctation of the aorta in adults and children # Guidance Current evidence on the safety and efficacy of balloon angioplasty with or without stenting for coarctation or recoarctation of the aorta in adults and children appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. The procedure should be performed by a multidisciplinary team in specialist centres with cardiac surgery facilities. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients into this database.# The procedure # Indications Aortic coarctation is a congenital narrowing of part of the aorta, most commonly the aortic arch, usually close to the origin of the left subclavian artery. This results in high blood pressure in the upper body and arms and low blood pressure in the legs. Standard treatment for native coarctation and recoarctation (see Section 2.2.1) involves open chest surgery. The type of surgery used depends on the anatomy of the lesion and preference of the surgeon, but may include resection of the coarctation site and end-to-end anastomosis repair, patch aortoplasty, left subclavian flap angioplasty, or bypass graft repair. # Outline of the procedure Balloon angioplasty of aortic coarctation is a minimally invasive procedure that involves inserting a catheter into a large blood vessel, usually in the groin, and passing it up to the narrowed area under radiological guidance. A balloon is then inflated within the narrowed area and a stent may be placed there to keep the area dilated. Balloon angioplasty and stenting may be carried out as a first treatment (in native coarctation) or if previous surgical or angioplasty fails and coarctation recurs (recoarctation). # Efficacy One small randomised controlled trial (RCT) was identified, along with a non-randomised comparative study and several case series. The RCT reported an 86% reduction in peak systolic pressure gradient in both the balloon angioplasty group and the surgery group. The non-randomised study comparing balloon angioplasty with and without stent placement reported a statistically significant reduction in peak systolic gradient of 83% in the angioplasty alone group and 96% in the angioplasty with stent group (p < 0.001). For more details, refer to the Sources of evidence section. One Specialist Advisor noted that results could be improved by concomitant stenting. Another considered residual stenosis to be an efficacy concern. # Safety In the RCT, the main complications reported were: aneurysm in 20% (4/20) of the angioplasty group and 0% (0/16) of the surgery group; diminished pulse (in the leg through which angioplasty was performed) in 10% (2/20) of the angioplasty group and 0% (0/16) of the surgery group; bleeding in 5% (1/20) of the angioplasty group and 13% (2/16) of the surgery group; and hypertension in 5% (1/20) of the angioplasty group and 0% (0/16) of the surgery group. For more details, refer to the Sources of evidence section. The Specialist Advisors considered the main potential adverse effects of the procedure to be death, aortic rupture, aneurysm, femoral artery damage, neurological damage and stroke. One Advisor noted that there were possible safety concerns if the procedure was performed for recoarctation after previous patch repair, but not for other types of surgery. # Other comments There were limited data on the use of the procedure in infants because these patients are usually treated surgically. The alternative to this procedure is major surgery. Andrew DillonChief ExecutiveJuly 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of balloon angioplasty or stenting for coarctation or recoarctation of the aorta', April 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication May: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of balloon angioplasty with or without stenting for coarctation or recoarctation of the aorta in adults and children appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nThe procedure should be performed by a multidisciplinary team in specialist centres with cardiac surgery facilities.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients into this database.', 'The procedure': '# Indications\n\nAortic coarctation is a congenital narrowing of part of the aorta, most commonly the aortic arch, usually close to the origin of the left subclavian artery. This results in high blood pressure in the upper body and arms and low blood pressure in the legs.\n\nStandard treatment for native coarctation and recoarctation (see Section 2.2.1) involves open chest surgery. The type of surgery used depends on the anatomy of the lesion and preference of the surgeon, but may include resection of the coarctation site and end-to-end anastomosis repair, patch aortoplasty, left subclavian flap angioplasty, or bypass graft repair.\n\n# Outline of the procedure\n\nBalloon angioplasty of aortic coarctation is a minimally invasive procedure that involves inserting a catheter into a large blood vessel, usually in the groin, and passing it up to the narrowed area under radiological guidance. A balloon is then inflated within the narrowed area and a stent may be placed there to keep the area dilated. Balloon angioplasty and stenting may be carried out as a first treatment (in native coarctation) or if previous surgical or angioplasty fails and coarctation recurs (recoarctation).\n\n# Efficacy\n\nOne small randomised controlled trial (RCT) was identified, along with a non-randomised comparative study and several case series. The RCT reported an 86% reduction in peak systolic pressure gradient in both the balloon angioplasty group and the surgery group. The non-randomised study comparing balloon angioplasty with and without stent placement reported a statistically significant reduction in peak systolic gradient of 83% in the angioplasty alone group and 96% in the angioplasty with stent group (p < 0.001). For more details, refer to the Sources of evidence section.\n\nOne Specialist Advisor noted that results could be improved by concomitant stenting. Another considered residual stenosis to be an efficacy concern.\n\n# Safety\n\nIn the RCT, the main complications reported were: aneurysm in 20% (4/20) of the angioplasty group and 0% (0/16) of the surgery group; diminished pulse (in the leg through which angioplasty was performed) in 10% (2/20) of the angioplasty group and 0% (0/16) of the surgery group; bleeding in 5% (1/20) of the angioplasty group and 13% (2/16) of the surgery group; and hypertension in 5% (1/20) of the angioplasty group and 0% (0/16) of the surgery group. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered the main potential adverse effects of the procedure to be death, aortic rupture, aneurysm, femoral artery damage, neurological damage and stroke. One Advisor noted that there were possible safety concerns if the procedure was performed for recoarctation after previous patch repair, but not for other types of surgery.\n\n# Other comments\n\nThere were limited data on the use of the procedure in infants because these patients are usually treated surgically.\n\nThe alternative to this procedure is major surgery.\n\nAndrew DillonChief ExecutiveJuly 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of balloon angioplasty or stenting for coarctation or recoarctation of the aorta', April 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nMay: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg74
b1fd4adcd5d84485fa74996adc709ec5517ce75f	nice	Lumbar subcutaneous shunt	Lumbar subcutaneous shunt # Guidance Current evidence on the safety and efficacy of lumbar subcutaneous shunt does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake lumbar subcutaneous shunt should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having lumbar subcutaneous shunt. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications This procedure is used to treat communicating hydrocephalus (normal pressure hydrocephalus) and benign intracranial hypertension (pseudotumour cerebri). Communicating hydrocephalus is an uncommon condition caused by excess cerebrospinal fluid collecting in the subarachnoid space. Causes include congenital abnormality, brain haemorrhage and meningitis, but in some cases, no cause is found. The symptoms include confusion, gait disturbance and urinary incontinence. Untreated, the condition may cause brain damage or death. Benign intracranial hypertension is an uncommon condition of unknown cause, in which the pressure of the cerebrospinal fluid is increased. The symptoms include headache, dizziness and visual problems. The prognosis is generally good, although a few people may experience permanent visual loss. # Outline of the procedure A cerebrospinal fluid shunt is a system of valved tubes that carries cerebrospinal fluid from the subarachnoid space to another part of the body to drain it and prevent damage to the brain or eyes. Usually, a shunt is tunnelled under the skin, with the upper end in a cerebral ventricle and the lower end in the heart (ventriculo–atrial shunt) or in the peritoneum (ventriculo–peritoneal shunt). Alternatively, the upper end of the shunt may be placed in the subarachnoid space in the lumbar part of the back, with the lower end draining fluid into the peritoneum (lumbar–peritoneal shunt). A lumbar subcutaneous shunt differs from the types of shunt described in section 2.2.1 in that the cerebrospinal fluid drains into the space immediately under the skin. A narrow tube is inserted percutaneously into the subarachnoid space in the lumbar part of the back and is tunnelled under the skin to a site where fluid can drain, usually in the flank or abdomen. The advantage is that general anaesthetic is not required, unlike for other shunt procedures. # Efficacy No studies reporting efficacy outcomes of lumbar subcutaneous shunt were identified. The Specialist Advisors noted that this procedure is only being undertaken by one surgeon in the UK. One Advisor was unsure about the efficacy of the procedure because the subcutaneous tissues do not absorb cerebrospinal fluid; however, data are being collected to investigate this. # Safety No studies reporting safety outcomes of lumbar subcutaneous shunt were identified. One Specialist Advisor considered the main potential adverse effects of the procedure to be infection, subdural haematoma and irritation of nerve roots.# Further information The surgeon who has been carrying out this procedure has been collecting data for several years on patients who have undergone the procedure, but there have been no publications to date. Andrew DillonChief ExecutiveJune 2004 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of lumbar subcutaneous shunt', December 2002. # Information for the public NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication As part of the NICE's work programme, the current guidance was considered for review but did not meet the review criteria as set out in the IP process guide. This guidance therefore remains current. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of lumbar subcutaneous shunt does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake lumbar subcutaneous shunt should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having lumbar subcutaneous shunt.\n\nPublication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.", 'The procedure': '# Indications\n\nThis procedure is used to treat communicating hydrocephalus (normal pressure hydrocephalus) and benign intracranial hypertension (pseudotumour cerebri).\n\nCommunicating hydrocephalus is an uncommon condition caused by excess cerebrospinal fluid collecting in the subarachnoid space. Causes include congenital abnormality, brain haemorrhage and meningitis, but in some cases, no cause is found. The symptoms include confusion, gait disturbance and urinary incontinence. Untreated, the condition may cause brain damage or death.\n\nBenign intracranial hypertension is an uncommon condition of unknown cause, in which the pressure of the cerebrospinal fluid is increased. The symptoms include headache, dizziness and visual problems. The prognosis is generally good, although a few people may experience permanent visual loss.\n\n# Outline of the procedure\n\nA cerebrospinal fluid shunt is a system of valved tubes that carries cerebrospinal fluid from the subarachnoid space to another part of the body to drain it and prevent damage to the brain or eyes. Usually, a shunt is tunnelled under the skin, with the upper end in a cerebral ventricle and the lower end in the heart (ventriculo–atrial shunt) or in the peritoneum (ventriculo–peritoneal shunt). Alternatively, the upper end of the shunt may be placed in the subarachnoid space in the lumbar part of the back, with the lower end draining fluid into the peritoneum (lumbar–peritoneal shunt).\n\nA lumbar subcutaneous shunt differs from the types of shunt described in section 2.2.1 in that the cerebrospinal fluid drains into the space immediately under the skin. A narrow tube is inserted percutaneously into the subarachnoid space in the lumbar part of the back and is tunnelled under the skin to a site where fluid can drain, usually in the flank or abdomen. The advantage is that general anaesthetic is not required, unlike for other shunt procedures.\n\n# Efficacy\n\nNo studies reporting efficacy outcomes of lumbar subcutaneous shunt were identified.\n\nThe Specialist Advisors noted that this procedure is only being undertaken by one surgeon in the UK. One Advisor was unsure about the efficacy of the procedure because the subcutaneous tissues do not absorb cerebrospinal fluid; however, data are being collected to investigate this.\n\n# Safety\n\nNo studies reporting safety outcomes of lumbar subcutaneous shunt were identified.\n\nOne Specialist Advisor considered the main potential adverse effects of the procedure to be infection, subdural haematoma and irritation of nerve roots.', 'Further information': "The surgeon who has been carrying out this procedure has been collecting data for several years on patients who have undergone the procedure, but there have been no publications to date.\n\nAndrew DillonChief ExecutiveJune 2004\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of lumbar subcutaneous shunt', December 2002.\n\n# Information for the public\n\nNICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': "As part of the NICE's work programme, the current guidance was considered for review but did not meet the review criteria as set out in the IP process guide. This guidance therefore remains current.\n\nJanuary 2012: minor maintenance.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg68
36fa790b78c102a4bf04ffaf53b4a493c4688ca3	nice	Balloon dilatation of pulmonary valve stenosis	Balloon dilatation of pulmonary valve stenosis # Guidance Current evidence on the safety and efficacy of balloon dilatation of pulmonary valve stenosis appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. Balloon dilatation of pulmonary valve stenosis should only be performed in a specialist unit where paediatric cardiac surgery is available. The Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients undergoing paediatric cardiovascular interventions onto this database.# The procedure # Indications Pulmonary valve stenosis is narrowing of the pulmonary valve in the heart. It is usually congenital. The outflow of blood from the right ventricle of the heart to the lungs is obstructed. Symptoms include shortness of breath, chest pains, fainting and, in some instances, sudden death. Balloon dilatation is an alternative to open surgical valvotomy. # Outline of the procedure Balloon dilatation is a minimally invasive transvenous procedure to dilate the pulmonary valve orifice during cardiac catheterisation. # Efficacy The evidence identified was limited to case series and one historical controlled study. All the studies reported a reduction in the residual pressure gradient across the pulmonary valve. In addition, the studies that reported data with more than 11 months follow-up showed that the reduction in pressure gradient persisted. In a case series of 533 children who received the procedure, an immediate residual gradient of less than 36 mmHg was reported in 74% (394/533) of patients. No clinical outcomes were reported. For more details, refer to the Sources of evidence section. The Specialist Advisors considered this procedure to be established practice and had no concerns about its efficacy. # Safety Most of the studies identified did not report safety findings in detail. The study that described safety findings in most detail reported the following immediate complications among 811 patients: arrhythmia, 1% (8/811); bleeding from catheter site, 0.9% (7/811); femoral vein thrombosis, 0.6% (5/811); hypoxia, 0.4% (3/811); death, 0.2% (2/811); tricuspid regurgitation, 0.2% (2/811); femoral vein tears, 0.2% (2/811); arterial thrombosis, 0.2% (2/811); cardiac perforation, 0.1% (1/811); and respiratory arrest, 0.1% (1/811). For more details, refer to the Sources of evidence section. The Specialist Advisors commented that pulmonary regurgitation was common after the procedure, but that the long-term effects of this were unknown. They considered the risks to be greater in neonates than in older infants and children. The Advisors also recommended that the procedure should be carried out only in paediatric cardiology units with special expertise. # Other comments This procedure has become established practice on the basis of clinical experience. There is very limited research evidence published. Most of the data relates to neonates and children, but the procedure can also be performed in adults.# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of balloon dilatation of pulmonary valve stenosis', March 2003. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication May: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of balloon dilatation of pulmonary valve stenosis appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nBalloon dilatation of pulmonary valve stenosis should only be performed in a specialist unit where paediatric cardiac surgery is available.\n\nThe Department of Health runs the UK Central Cardiac Audit Database (UKCCAD) and clinicians are encouraged to enter all patients undergoing paediatric cardiovascular interventions onto this database.', 'The procedure': '# Indications\n\nPulmonary valve stenosis is narrowing of the pulmonary valve in the heart. It is usually congenital. The outflow of blood from the right ventricle of the heart to the lungs is obstructed. Symptoms include shortness of breath, chest pains, fainting and, in some instances, sudden death.\n\nBalloon dilatation is an alternative to open surgical valvotomy.\n\n# Outline of the procedure\n\nBalloon dilatation is a minimally invasive transvenous procedure to dilate the pulmonary valve orifice during cardiac catheterisation.\n\n# Efficacy\n\nThe evidence identified was limited to case series and one historical controlled study. All the studies reported a reduction in the residual pressure gradient across the pulmonary valve. In addition, the studies that reported data with more than 11 months follow-up showed that the reduction in pressure gradient persisted. In a case series of 533 children who received the procedure, an immediate residual gradient of less than 36 mmHg was reported in 74% (394/533) of patients. No clinical outcomes were reported. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered this procedure to be established practice and had no concerns about its efficacy.\n\n# Safety\n\nMost of the studies identified did not report safety findings in detail. The study that described safety findings in most detail reported the following immediate complications among 811 patients: arrhythmia, 1% (8/811); bleeding from catheter site, 0.9% (7/811); femoral vein thrombosis, 0.6% (5/811); hypoxia, 0.4% (3/811); death, 0.2% (2/811); tricuspid regurgitation, 0.2% (2/811); femoral vein tears, 0.2% (2/811); arterial thrombosis, 0.2% (2/811); cardiac perforation, 0.1% (1/811); and respiratory arrest, 0.1% (1/811). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors commented that pulmonary regurgitation was common after the procedure, but that the long-term effects of this were unknown. They considered the risks to be greater in neonates than in older infants and children. The Advisors also recommended that the procedure should be carried out only in paediatric cardiology units with special expertise.\n\n# Other comments\n\nThis procedure has become established practice on the basis of clinical experience. There is very limited research evidence published.\n\nMost of the data relates to neonates and children, but the procedure can also be performed in adults.', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of balloon dilatation of pulmonary valve stenosis', March 2003.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nMay: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg67
1fa04f517fbb2e60d090b5cd8732d2a435cf3cee	nice	Insertion of hydrogel keratoprosthesis	Insertion of hydrogel keratoprosthesis # Guidance Current evidence on the safety and efficacy of insertion of hydrogel keratoprosthesis does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake insertion of hydrogel keratoprosthesis should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having insertion of hydrogel keratoprosthesis. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The manufacturer of the synthetic hydrogel cornea implant used in this procedure maintains a registry . The Institute may review the procedure upon publication of further evidence.# The procedure # Indications The cornea is the transparent part of the coating of the eyeball, that covers the iris and pupil and admits light to the interior of the eye. Injury or disease of the cornea can make it opaque, hindering the passage of light and resulting in loss of vision. Diseases that can cause the cornea to deteriorate include keratoconus, bullous keratopathy and herpetic eye disease. A corneal transplant is the standard treatment when the cornea becomes damaged by injury or disease. This procedure involves the removal of a disc comprising the majority of the cornea using a trephine, and replacing it with a corresponding disc from the cornea of a donor eye. In penetrating keratoplasty, a disc the entire thickness of the cornea is removed and replaced with a disc of equivalent thickness. Some patients cannot undergo the standard procedure using donor tissue for several reasons, such as disease severity, severe involvement of the conjunctiva, objection to the use of donor tissue, failed past donor tissue transplants, or when measures required to prevent graft rejection are medically contraindicated. For these patients, penetrating keratoplasty using an artificial cornea or keratoprosthesis is an option. # Outline of the procedure The implantation of a synthetic hydrogel cornea is a two-stage surgical procedure. The first stage involves making a partial thickness incision at the junction of the cornea and sclera, to allow an intralamellar pocket to be created within the cornea. The superficial flap is then reflected to allow a portion of the central part of the posterior lamella to be removed using a trephine, and the synthetic hydrogel cornea to be inserted into the intralamellar pocket. The superficial flap is repositioned and the incision closed. In most cases, the operation is completed by forming a flap of tissue from the conjunctiva, which is used to cover the surface of the front of the eye. This may cause changes in the cosmetic appearance of the eye. The second stage of the procedure is performed 12 weeks later, and involves removing the conjunctival cover and the superficial flap of the cornea, exposing the synthetic hydrogel cornea to light. The eye may still not appear completely 'normal' after this stage of the operation. # Efficacy Evidence on the efficacy of this procedure was based on small, uncontrolled studies with short-term follow-up. Initial results indicated that visual acuity improved (although it was still poor) or remained the same in most patients. In a report of 41 patients with a mean preoperative visual acuity of hand movements, mean best corrected visual acuity for 21 patients at 12 months follow-up was 20/300. An improvement of this degree is likely to be valuable to patients. The authors of this report also stated that among the 41 patients undergoing implant of a synthetic cornea, 26 implants remained in situ (63%) at a mean follow-up of 16 months. However, patient selection criteria have changed since the first trial of this procedure, and it is unclear what impact this will have on efficacy outcomes. For more details, refer to the Sources of evidence section. The Specialist Advisors considered that this procedure should be restricted to those individuals who cannot be treated with established procedures and who have no useful vision in the other eye. # Safety Stromal melting is a frequent complication for all keratoprostheses and is common following this procedure. In a review of 41 non-herpetic patients, 42% (17 patients) developed a stromal melt. In this particular review, the number of patients requiring device removal as a result of this complication was unclear; however, in another series, the same authors reported that 13% (5/40) implants were removed because of melting. Other complications included cellular depositions on the device itself (22%), development of retroprosthetic membranes (7%), and retinal detachment (5%). The literature seemed to suggest that certain patients were at increased risk of complications, namely patients with herpetic eye disease and smokers. For more details, refer to the Sources of evidence section. The Specialist Advisors considered that the long-term complication rate of this procedure is still unknown. Although endophthalmitis is thought to be the most significant potential complication of any artificial cornea, the Advisors noted that this had not yet been reported following this procedure. # Other comments Data were based on small numbers of patients. Andrew DillonChief ExecutiveJune 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of insertion of hydrogel keratoprosthesis', October 2003. # Information for the public NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication The guidance was considered for reassessment in June 2007 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of insertion of hydrogel keratoprosthesis does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake insertion of hydrogel keratoprosthesis should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having insertion of hydrogel keratoprosthesis.\n\nPublication of safety and efficacy outcomes will be useful in reducing the current uncertainty.\n\nThe manufacturer of the synthetic hydrogel cornea implant used in this procedure maintains a registry [link broken, Feb2012]. The Institute may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nThe cornea is the transparent part of the coating of the eyeball, that covers the iris and pupil and admits light to the interior of the eye. Injury or disease of the cornea can make it opaque, hindering the passage of light and resulting in loss of vision. Diseases that can cause the cornea to deteriorate include keratoconus, bullous keratopathy and herpetic eye disease.\n\nA corneal transplant is the standard treatment when the cornea becomes damaged by injury or disease. This procedure involves the removal of a disc comprising the majority of the cornea using a trephine, and replacing it with a corresponding disc from the cornea of a donor eye. In penetrating keratoplasty, a disc the entire thickness of the cornea is removed and replaced with a disc of equivalent thickness. Some patients cannot undergo the standard procedure using donor tissue for several reasons, such as disease severity, severe involvement of the conjunctiva, objection to the use of donor tissue, failed past donor tissue transplants, or when measures required to prevent graft rejection are medically contraindicated. For these patients, penetrating keratoplasty using an artificial cornea or keratoprosthesis is an option.\n\n# Outline of the procedure\n\nThe implantation of a synthetic hydrogel cornea is a two-stage surgical procedure. The first stage involves making a partial thickness incision at the junction of the cornea and sclera, to allow an intralamellar pocket to be created within the cornea. The superficial flap is then reflected to allow a portion of the central part of the posterior lamella to be removed using a trephine, and the synthetic hydrogel cornea to be inserted into the intralamellar pocket. The superficial flap is repositioned and the incision closed. In most cases, the operation is completed by forming a flap of tissue from the conjunctiva, which is used to cover the surface of the front of the eye. This may cause changes in the cosmetic appearance of the eye.\n\nThe second stage of the procedure is performed 12 weeks later, and involves removing the conjunctival cover and the superficial flap of the cornea, exposing the synthetic hydrogel cornea to light. The eye may still not appear completely 'normal' after this stage of the operation.\n\n# Efficacy\n\nEvidence on the efficacy of this procedure was based on small, uncontrolled studies with short-term follow-up. Initial results indicated that visual acuity improved (although it was still poor) or remained the same in most patients. In a report of 41 patients with a mean preoperative visual acuity of hand movements, mean best corrected visual acuity for 21 patients at 12 months follow-up was 20/300. An improvement of this degree is likely to be valuable to patients. The authors of this report also stated that among the 41 patients undergoing implant of a synthetic cornea, 26 implants remained in situ (63%) at a mean follow-up of 16 months. However, patient selection criteria have changed since the first trial of this procedure, and it is unclear what impact this will have on efficacy outcomes. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered that this procedure should be restricted to those individuals who cannot be treated with established procedures and who have no useful vision in the other eye.\n\n# Safety\n\nStromal melting is a frequent complication for all keratoprostheses and is common following this procedure. In a review of 41 non-herpetic patients, 42% (17 patients) developed a stromal melt. In this particular review, the number of patients requiring device removal as a result of this complication was unclear; however, in another series, the same authors reported that 13% (5/40) implants were removed because of melting. Other complications included cellular depositions on the device itself (22%), development of retroprosthetic membranes (7%), and retinal detachment (5%). The literature seemed to suggest that certain patients were at increased risk of complications, namely patients with herpetic eye disease and smokers. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered that the long-term complication rate of this procedure is still unknown. Although endophthalmitis is thought to be the most significant potential complication of any artificial cornea, the Advisors noted that this had not yet been reported following this procedure.\n\n# Other comments\n\nData were based on small numbers of patients.\n\nAndrew DillonChief ExecutiveJune 2004", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of insertion of hydrogel keratoprosthesis', October 2003.\n\n# Information for the public\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': 'The guidance was considered for reassessment in June 2007 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg69
ad2ea01b171a8df7cea65f4bbb0788c827bbd339	nice	Artificial anal sphincter implantation	Artificial anal sphincter implantation # Guidance Current evidence on the safety and efficacy of artificial anal sphincter implantation does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake artificial anal sphincter implantation should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having artificial anal sphincter implantation. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence. It is recommended that this procedure is carried out only in units with a specialist interest in faecal incontinence.# The procedure # Indications The causes of faecal incontinence are diverse. Existing treatment options include medical therapy, biofeedback techniques and surgery in selected patients. Surgical treatments include sphincter repair, sacral nerve stimulation, encirclement procedures and muscle transposition (for example, dynamic graciloplasty). Some patients may require acolostomy if other treatments fail. # Outline of the procedure Implantation of an artificial anal sphincter is used to treat severe faecal incontinence. In this procedure, a fluid-filled cuff is implanted around the anal canal. Tubing from the cuff is channelled under the skin of the perineum and connected to a control pump placed subcutaneously in the scrotum or labia. The control pump is connected by tubing to a pressure-regulating balloon implanted in the abdominal wall. The cuff simulates the natural function of the sphincter muscle; when the fluid is displaced from the cuff to the balloon via the patient-controlled pump, defaecation can take place. Once defaecation is complete, the fluid is slowly returned to the cuff and continence is again achieved. For more details, refer to the Sources of evidence section. # Efficacy No controlled studies were identified. Some of the studies identified were small and some had high losses to follow-up. Among the studies identified, removal of the artificial sphincter system was required in 19% (10/53) to 41% (7/17) of patients. In patients who had not undergone explantation, all the studies showed improvement in continence. However, different measures of continence were used in the studies. The studies that reported manometric results showed increased mean anal pressures after implantation. For more details, refer to the Sources of evidence section. The Specialist Advisors considered the main efficacy concern to be the frequent need to remove the implanted artificial sphincter. # Safety The largest study identified reported that device-related complications occurred in 86% (99/115) of patients. The most common adverse events reported in this study were: infection 33% (38/115); pain 32% (37/115); erosion 21% (24/115); faecal impaction 18% (21/115); faecal incontinence 18% (21/115); constipation 17% (20/115); surgical injury 13% (15/115); wound problems 10% (11/115); difficult evacuation 9% (10/115); and wound dehiscence 9% (10/115). For more details, refer to the Sources of evidence section. The Specialist Advisors considered the main safety concerns to be infection, erosion and evacuation difficulties. # Other comments The procedure may have a place in the treatment of patients who are unsuitable for sacral nerve stimulation. There is a significant rate of complications, such as infection, cuff erosion, wound dehiscence and haematoma, and patients may require revisional surgery or removal of the device. Fully informed consent is therefore particularly important. Andrew DillonChief ExecutiveJune 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of artificial anal sphincter implantation', November 2002. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication The guidance was considered for reassessment in June 2007 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of artificial anal sphincter implantation does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake artificial anal sphincter implantation should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having artificial anal sphincter implantation.\n\nPublication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.\n\nIt is recommended that this procedure is carried out only in units with a specialist interest in faecal incontinence.", 'The procedure': '# Indications\n\nThe causes of faecal incontinence are diverse. Existing treatment options include medical therapy, biofeedback techniques and surgery in selected patients. Surgical treatments include sphincter repair, sacral nerve stimulation, encirclement procedures and muscle transposition (for example, dynamic graciloplasty). Some patients may require acolostomy if other treatments fail.\n\n# Outline of the procedure\n\nImplantation of an artificial anal sphincter is used to treat severe faecal incontinence. In this procedure, a fluid-filled cuff is implanted around the anal canal. Tubing from the cuff is channelled under the skin of the perineum and connected to a control pump placed subcutaneously in the scrotum or labia. The control pump is connected by tubing to a pressure-regulating balloon implanted in the abdominal wall. The cuff simulates the natural function of the sphincter muscle; when the fluid is displaced from the cuff to the balloon via the patient-controlled pump, defaecation can take place. Once defaecation is complete, the fluid is slowly returned to the cuff and continence is again achieved. For more details, refer to the Sources of evidence section.\n\n# Efficacy\n\nNo controlled studies were identified. Some of the studies identified were small and some had high losses to follow-up. Among the studies identified, removal of the artificial sphincter system was required in 19% (10/53) to 41% (7/17) of patients. In patients who had not undergone explantation, all the studies showed improvement in continence. However, different measures of continence were used in the studies. The studies that reported manometric results showed increased mean anal pressures after implantation. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered the main efficacy concern to be the frequent need to remove the implanted artificial sphincter.\n\n# Safety\n\nThe largest study identified reported that device-related complications occurred in 86% (99/115) of patients. The most common adverse events reported in this study were: infection 33% (38/115); pain 32% (37/115); erosion 21% (24/115); faecal impaction 18% (21/115); faecal incontinence 18% (21/115); constipation 17% (20/115); surgical injury 13% (15/115); wound problems 10% (11/115); difficult evacuation 9% (10/115); and wound dehiscence 9% (10/115). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered the main safety concerns to be infection, erosion and evacuation difficulties.\n\n# Other comments\n\nThe procedure may have a place in the treatment of patients who are unsuitable for sacral nerve stimulation.\n\nThere is a significant rate of complications, such as infection, cuff erosion, wound dehiscence and haematoma, and patients may require revisional surgery or removal of the device. Fully informed consent is therefore particularly important.\n\nAndrew DillonChief ExecutiveJune 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of artificial anal sphincter implantation', November 2002.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': 'The guidance was considered for reassessment in June 2007 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg66
0ab371eb536121b2a88fdd294e6e56b435ca995c	nice	Sacral nerve stimulation for urge incontinence and urgency-frequency	Sacral nerve stimulation for urge incontinence and urgency-frequency # Guidance This document replaced previous guidance on sacral nerve stimulation for 'Urge incontinence' (NICE Interventional Procedures Guidance no. 4) after the Interventional Procedures Advisory Committee reconsidered the procedure based on the results of a systematic review commissioned by NICE. Current evidence on the safety and efficacy of sacral nerve stimulation for urge incontinence and urgency-frequency appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Patient selection is important. The diagnosis should be defined as clearly as possible and the procedure limited to patients who have not responded to conservative treatments such as lifestyle modifications, behavioural techniques and drug therapy. Patients should be selected on the basis of their response to peripheral nerve evaluation.# The procedure # Indications Sacral nerve stimulation is used to treat the symptoms of an overactive bladder, including urinary urge incontinence and/or urgency frequency in patients who have failed or cannot tolerate conventional treatments. In patients for whom conservative treatments have been unsuccessful, the standard alternatives include bladder reconstruction (such as augmentation and cystoplasty) and urinary diversion. # Outline of the procedure Sacral nerve stimulation involves applying an electric current to one of the sacral nerves via an electrode placed through the corresponding sacral foramen. The electrode leads are attached to an implantable pulse generator, which stimulates nerves associated with the lower urinary tract. # Efficacy This procedure was subject to a systematic review commissioned by the Institute in November 2003. Evidence from two randomised controlled trials (RCTs), including a total of 50 patients with urge incontinence, showed that complete continence (completely dry with no incontinent episodes) or improvement of more than 50% in incontinence symptoms was observed in 50% and 80% of patients, respectively, following the procedure. This compared with 5% of patients in the control groups, who were receiving conservative treatments while waiting for an implant. In the one RCT that reported on patients with urgency-frequency, an improvement of more than 50% in incontinence symptoms was observed in 56% (14/25) of patients, compared with 4% (1/25) in the control group. More evidence is available for patients with urge incontinence than for those with urgency-frequency. For more details, refer to the Sources of evidence section. The results of the case series studies included in the systematic review showed similar results, with complete continence and improvement in symptoms being reported in 39% (139/361) and 67% (338/501) of patients with urge incontinence, respectively, and 41% (22/54) and 65% (75/116) of patients with urgency-frequency, respectively. The benefits of sacral nerve stimulation were reported to persist for at least 3–5 years after implantation. For more details, refer to the Sources of evidence section. # Safety In general, evidence on the safety of this procedure was not well reported. Most complications observed in the studies were the result of technical problems related to implantation of the device. The results of the systematic review showed that, overall, the re-operation rate for patients with implants was 33% (283/860). The most common reasons for surgical revision were to replace or reposition implants due to pain or infection at the implant site, or to adjust and modify the lead system to correct breakage or migration. For more details, refer to the Sources of evidence section. Pain at the site of the pulse generator or at the site of stimulation was reported in 24% (162/663) of patients, sometimes requiring replacement and repositioning of the pulse generator. Other complications included lead-related problems such as migration (16%), wound problems (7%), adverse effects on bowel function (6%), and infection (5%). No cases of long-lasting neurological complications were identified. For more details, refer to the Sources of evidence section. # Other comments There is a lack of long-term quality of life data. There is limited evidence relating to the use of this procedure in older patients. Andrew DillonChief ExecutiveJune 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Brazzelli M, Murray A, Fraser C, Grant A. Systematic review of the efficacy and safety of sacral nerve stimulation for urinary urge incontinence and urgency-frequency. Aberdeen: Review Body for Interventional Procedures; 2003'. Commissioned by the National Institute for Clinical Excellence. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Other NICE recommendations on sacral nerve stimulation Further recommendations have been made as part of the clinical guideline on lower urinary tract symptoms published in May 2010, as follows: Consider offering implanted sacral nerve stimulation to manage detrusor overactivity only to men whose symptoms have not responded to conservative management and drug treatments. Clinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available. The IP guidance on sacral nerve stimulation for urge incontinence and urgency-frequency remains current, and should be read in conjunction with the clinical guideline.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It updates and replaces NICE interventional procedure guidance 4. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "This document replaced previous guidance on sacral nerve stimulation for 'Urge incontinence' (NICE Interventional Procedures Guidance no. 4) after the Interventional Procedures Advisory Committee reconsidered the procedure based on the results of a systematic review commissioned by NICE.\n\nCurrent evidence on the safety and efficacy of sacral nerve stimulation for urge incontinence and urgency-frequency appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nPatient selection is important. The diagnosis should be defined as clearly as possible and the procedure limited to patients who have not responded to conservative treatments such as lifestyle modifications, behavioural techniques and drug therapy. Patients should be selected on the basis of their response to peripheral nerve evaluation.", 'The procedure': '# Indications\n\nSacral nerve stimulation is used to treat the symptoms of an overactive bladder, including urinary urge incontinence and/or urgency frequency in patients who have failed or cannot tolerate conventional treatments.\n\nIn patients for whom conservative treatments have been unsuccessful, the standard alternatives include bladder reconstruction (such as augmentation and cystoplasty) and urinary diversion.\n\n# Outline of the procedure\n\nSacral nerve stimulation involves applying an electric current to one of the sacral nerves via an electrode placed through the corresponding sacral foramen. The electrode leads are attached to an implantable pulse generator, which stimulates nerves associated with the lower urinary tract.\n\n# Efficacy\n\nThis procedure was subject to a systematic review commissioned by the Institute in November 2003. Evidence from two randomised controlled trials (RCTs), including a total of 50 patients with urge incontinence, showed that complete continence (completely dry with no incontinent episodes) or improvement of more than 50% in incontinence symptoms was observed in 50% and 80% of patients, respectively, following the procedure. This compared with 5% of patients in the control groups, who were receiving conservative treatments while waiting for an implant. In the one RCT that reported on patients with urgency-frequency, an improvement of more than 50% in incontinence symptoms was observed in 56% (14/25) of patients, compared with 4% (1/25) in the control group. More evidence is available for patients with urge incontinence than for those with urgency-frequency. For more details, refer to the Sources of evidence section.\n\nThe results of the case series studies included in the systematic review showed similar results, with complete continence and improvement in symptoms being reported in 39% (139/361) and 67% (338/501) of patients with urge incontinence, respectively, and 41% (22/54) and 65% (75/116) of patients with urgency-frequency, respectively. The benefits of sacral nerve stimulation were reported to persist for at least 3–5 years after implantation. For more details, refer to the Sources of evidence section.\n\n# Safety\n\nIn general, evidence on the safety of this procedure was not well reported. Most complications observed in the studies were the result of technical problems related to implantation of the device. The results of the systematic review showed that, overall, the re-operation rate for patients with implants was 33% (283/860). The most common reasons for surgical revision were to replace or reposition implants due to pain or infection at the implant site, or to adjust and modify the lead system to correct breakage or migration. For more details, refer to the Sources of evidence section.\n\nPain at the site of the pulse generator or at the site of stimulation was reported in 24% (162/663) of patients, sometimes requiring replacement and repositioning of the pulse generator. Other complications included lead-related problems such as migration (16%), wound problems (7%), adverse effects on bowel function (6%), and infection (5%). No cases of long-lasting neurological complications were identified. For more details, refer to the Sources of evidence section.\n\n# Other comments\n\nThere is a lack of long-term quality of life data.\n\nThere is limited evidence relating to the use of this procedure in older patients.\n\nAndrew DillonChief ExecutiveJune 2004', 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Brazzelli M, Murray A, Fraser C, Grant A. Systematic review of the efficacy and safety of sacral nerve stimulation for urinary urge incontinence and urgency-frequency. Aberdeen: Review Body for Interventional Procedures; 2003'. Commissioned by the National Institute for Clinical Excellence.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Other NICE recommendations on sacral nerve stimulation': 'Further recommendations have been made as part of the clinical guideline on lower urinary tract symptoms published in May 2010, as follows:\n\nConsider offering implanted sacral nerve stimulation to manage detrusor overactivity only to men whose symptoms have not responded to conservative management and drug treatments.\n\nClinical and cost-effectiveness evidence was reviewed in the development of this guideline which has led to this more specific recommendation. More information is available.\n\nThe IP guidance on sacral nerve stimulation for urge incontinence and urgency-frequency remains current, and should be read in conjunction with the clinical guideline.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt updates and replaces NICE interventional procedure guidance 4.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg64
9f197153c9824d415a84b3aba86ceef3f2f348d2	nice	Laser sheath removal of pacing leads	Laser sheath removal of pacing leads # Guidance Current evidence on the safety and efficacy of laser sheath removal of pacing leads appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Laser sheath removal of pacing leads should be used only in patients for whom standard methods of removal are ineffective.# The procedure # Indications This procedure is used to remove pacemaker leads that have been in place for a few months. Pacemaker leads may need to be removed or changed if they malfunction, cause heart rhythm problems or become infected. If the leads have been in place for more than a few months they can become tightly attached by scar tissue to the heart and to the veins through which they pass, making removal difficult and risky. This procedure may also be used to remove defibrillator leads. The conventional technique for removing pacing leads involves inserting locking stylets and telescoping sheaths around the pacing leads to separate them from the surrounding scar tissue. If this fails, open chest surgery may be required. Alternatively, in some cases, the leads may be detached from the pacemaker unit and simply left inside the patient. # Outline of the procedure Laser sheaths are similar to standard extraction sheaths, but vaporise rather than tear the scar tissue surrounding the pacing leads. The use of laser sheaths involves passing a double-layered sheath over the pacing leads. The inner layer of the sheath is made from fibre-optic material that transmits a laser beam; the outer layer is more rigid. The double-layered sheath is passed slowly over the lead and laser energy vaporises the scar tissue around the lead as the sheath is advanced over it. When scar tissue has been vaporised up to a point near the heart, the more rigid outer sheath is advanced to provide countertraction for removal of the pacing lead. # Efficacy In the studies reviewed, complete lead removal ranged from 89% (596/671 leads) to 98% (44/45 leads). In a randomised controlled trial, complete lead removal was 94% (230/244 leads) for patients in the laser group and 64% (142/221 leads) for patients in the non-laser group. In the same study, mean operation time per lead was 11 minutes in the laser group compared with 15 minutes in the non-laser group (p < 0.04). For more details, refer to the Sources of evidence section. The Specialist Advisors had no concerns about the efficacy of this procedure. They considered it to be at least as efficacious as, and probably more efficacious than, standard techniques. # Safety In a randomised controlled trial, 3 of 153 patients randomised to laser sheath removal required subsequent surgery (two patients required a thorocotomy and one patient required a chest tube). One patient later died after a cardiac tamponade, but this was not directly related to the use of laser energy. In the largest case series, major complications (defined as cardiac tamponade, haemothorax, pulmonary embolism, lead migration and death) were observed in 2% (31/1684) of patients, and 1% (13/1684) of patients died in hospital. For more details, refer to the Sources of evidence section. The Specialist Advisors considered the complications of laser sheath removal of pacing leads to be similar to those of standard extraction techniques. They commented on the small risk of cardiac tamponade caused by rupture of major veins or the myocardium, and noted that this could result in the need for emergency surgery and, in some cases, cause death. # Other comments Removal of pacing leads can cause serious complications, requiring cardiac surgery, regardless of the extraction technique used. Andrew DillonChief ExecutiveJune 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of laser sheath removal of pacing leads', December 2002. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of laser sheath removal of pacing leads appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.\n\nLaser sheath removal of pacing leads should be used only in patients for whom standard methods of removal are ineffective.', 'The procedure': '# Indications\n\nThis procedure is used to remove pacemaker leads that have been in place for a few months. Pacemaker leads may need to be removed or changed if they malfunction, cause heart rhythm problems or become infected. If the leads have been in place for more than a few months they can become tightly attached by scar tissue to the heart and to the veins through which they pass, making removal difficult and risky. This procedure may also be used to remove defibrillator leads.\n\nThe conventional technique for removing pacing leads involves inserting locking stylets and telescoping sheaths around the pacing leads to separate them from the surrounding scar tissue. If this fails, open chest surgery may be required. Alternatively, in some cases, the leads may be detached from the pacemaker unit and simply left inside the patient.\n\n# Outline of the procedure\n\nLaser sheaths are similar to standard extraction sheaths, but vaporise rather than tear the scar tissue surrounding the pacing leads. The use of laser sheaths involves passing a double-layered sheath over the pacing leads. The inner layer of the sheath is made from fibre-optic material that transmits a laser beam; the outer layer is more rigid. The double-layered sheath is passed slowly over the lead and laser energy vaporises the scar tissue around the lead as the sheath is advanced over it. When scar tissue has been vaporised up to a point near the heart, the more rigid outer sheath is advanced to provide countertraction for removal of the pacing lead.\n\n# Efficacy\n\nIn the studies reviewed, complete lead removal ranged from 89% (596/671 leads) to 98% (44/45 leads). In a randomised controlled trial, complete lead removal was 94% (230/244 leads) for patients in the laser group and 64% (142/221 leads) for patients in the non-laser group. In the same study, mean operation time per lead was 11 minutes in the laser group compared with 15 minutes in the non-laser group (p < 0.04). For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors had no concerns about the efficacy of this procedure. They considered it to be at least as efficacious as, and probably more efficacious than, standard techniques.\n\n# Safety\n\nIn a randomised controlled trial, 3 of 153 patients randomised to laser sheath removal required subsequent surgery (two patients required a thorocotomy and one patient required a chest tube). One patient later died after a cardiac tamponade, but this was not directly related to the use of laser energy. In the largest case series, major complications (defined as cardiac tamponade, haemothorax, pulmonary embolism, lead migration and death) were observed in 2% (31/1684) of patients, and 1% (13/1684) of patients died in hospital. For more details, refer to the Sources of evidence section.\n\nThe Specialist Advisors considered the complications of laser sheath removal of pacing leads to be similar to those of standard extraction techniques. They commented on the small risk of cardiac tamponade caused by rupture of major veins or the myocardium, and noted that this could result in the need for emergency surgery and, in some cases, cause death.\n\n# Other comments\n\nRemoval of pacing leads can cause serious complications, requiring cardiac surgery, regardless of the extraction technique used.\n\nAndrew DillonChief ExecutiveJune 2004', 'Further information ': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of laser sheath removal of pacing leads', December 2002.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg63
4ebc71af52d577b0b554b02e959370e4ca7ee3b0	nice	Falloposcopy with coaxial catheter	Falloposcopy with coaxial catheter # Guidance Current evidence on the safety and efficacy of falloposcopy with coaxial catheter does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake falloposcopy with coaxial catheter should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having falloposcopy with coaxial catheter. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Falloposcopy with coaxial catheter is used to investigate and treat subfertility in women. Conventional investigation of subfertility in women often includes examination of the fallopian tubes using hysterosalpingography, or laparoscopy with dye injection, to check the patency of the fallopian tubes. Occasionally, salpingoscopy is performed – this involves inspection of the inside of the fallopian tubes from the outer fimbrial end during laparoscopy or laparotomy. # Outline of the procedure Falloposcopy with coaxial catheter is a technique for direct inspection of the inside of the fallopian tubes via the cervix and uterus. The coaxial technique involves inserting a narrow catheter over a guidewire through the cervix and uterine cavity into a fallopian tube. The surgeon then passes an endoscope through the catheter. Unlike X-ray methods or laparoscopy, falloposcopy allows balloon dilatation to be performed on obstructive lesions at the time of the procedure. # Efficacy No controlled studies were found, and none of the studies identified were of high quality. Some studies were on the investigative use of falloposcopy with coaxial catheter and others looked at the procedure as a therapeutic technique. Among the studies on investigation, the rate of successful fallopian tube cannulation/catheterisation ranged from 83% (30/36) to 85% (110/130). In two studies, the failure rate of falloposcopy was 11% (9/84 and 8/71), but some women may have been included in both studies. Successful imaging or 'correct' visualisation of the fallopian tube ranged from 30% (33/110) to 88% (28/32). One of the studies on the procedure's therapeutic use found coaxial falloposcopy with direct balloon tuboplasty to be successful in treating endotubal lesions in 41% (13/32) of tubes. Another study reported 96% (52/54) of recanalisations to be technically successful, but of the tubes successfully recanalised, only 31% (16/52) were as a result of falloposcopy with coaxial catheter (the other 36 were treated by selective salpingography). Five pregnancies occurred in this study, but it was not possible to determine whether these occurred in women who underwent falloposcopy with coaxial catheter. One comparative study on the consistency between the results of hysterosalpingography and falloposcopy was identified. In this study, only 15% (3/20) of tubes found to be blocked when using hysterosalpingography were found to be blocked when using falloposcopy. However, no 'gold standard' test was available to determine the validity of the results. For more details, refer to the 'Sources of evidence' section. One Specialist Advisor noted that the images obtained by falloposcopy with coaxial catheter were often of poor quality and the 'normal' internal appearance of the tube was not clearly defined. # Safety In the studies identified, the main complications reported were: tubal perforation, which occurred in 1% (1/130) to 4% (3/67) of tubes; and uterine perforation, which occurred during procedures on 2% (3/130) of tubes. One study reported a complication rate of 23% (3/13) for distal fallopian tube obstructions, but it was not clear whether these women had undergone falloposcopy with coaxial catheter. For more details, refer to the 'Sources of evidence' section. One Specialist Advisor considered the main potential adverse effect of this procedure to be perforation of the fallopian tube; this is usually a minor complication. # Other comments This is one of a number of techniques for examining the fallopian tubes, but it is seldom used in the UK. Andrew DillonChief ExecutiveJune 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of falloposcopy with coaxial catheter', November 2002. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication As part of the NICE's work programme, the current guidance was considered for review but did not meet the review criteria as set out in the IP process guide. This guidance therefore remains current. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of falloposcopy with coaxial catheter does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake falloposcopy with coaxial catheter should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety\n\nand efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having falloposcopy with coaxial catheter.\n\nPublication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nFalloposcopy with coaxial catheter is used to investigate and treat subfertility in women.\n\nConventional investigation of subfertility in women often includes examination of the fallopian tubes using hysterosalpingography, or laparoscopy with dye injection, to check the patency of the fallopian tubes. Occasionally, salpingoscopy is performed – this involves inspection of the inside of the fallopian tubes from the outer fimbrial end during laparoscopy or laparotomy.\n\n# Outline of the procedure\n\nFalloposcopy with coaxial catheter is a technique for direct inspection of the inside of the fallopian tubes via the cervix and uterus. The coaxial technique involves inserting a narrow catheter over a guidewire through the cervix and uterine cavity into a fallopian tube. The surgeon then passes an endoscope through the catheter. Unlike X-ray methods or laparoscopy, falloposcopy allows balloon dilatation to be performed on obstructive lesions at the time of the procedure.\n\n# Efficacy\n\nNo controlled studies were found, and none of the studies identified were of high quality. Some studies were on the investigative use of falloposcopy with coaxial catheter and others looked at the procedure as a therapeutic technique.\n\nAmong the studies on investigation, the rate of successful fallopian tube cannulation/catheterisation ranged from 83% (30/36) to 85% (110/130). In two studies, the failure rate of falloposcopy was 11% (9/84 and 8/71), but some women may have been included in both studies. Successful imaging or 'correct' visualisation of the fallopian tube ranged from 30% (33/110) to 88% (28/32).\n\nOne of the studies on the procedure's therapeutic use found coaxial falloposcopy with direct balloon tuboplasty to be successful in treating endotubal lesions in 41% (13/32) of tubes. Another study reported 96% (52/54) of recanalisations to be technically successful, but of the tubes successfully recanalised, only 31% (16/52) were as a result of falloposcopy with coaxial catheter (the other 36 were treated by selective salpingography). Five pregnancies occurred in this study, but it was not possible to determine whether these occurred in women who underwent falloposcopy with coaxial catheter.\n\nOne comparative study on the consistency between the results of hysterosalpingography and falloposcopy was identified. In this study, only 15% (3/20) of tubes found to be blocked when using hysterosalpingography were found to be blocked when using falloposcopy. However, no 'gold standard' test was available to determine the validity of the results. For more details, refer to the 'Sources of evidence' section.\n\nOne Specialist Advisor noted that the images obtained by falloposcopy with coaxial catheter were often of poor quality and the 'normal' internal appearance of the tube was not clearly defined.\n\n# Safety\n\nIn the studies identified, the main complications reported were: tubal perforation, which occurred in 1% (1/130) to 4% (3/67) of tubes; and uterine perforation, which occurred during procedures on 2% (3/130) of tubes. One study reported a complication rate of 23% (3/13) for distal fallopian tube obstructions, but it was not clear whether these women had undergone falloposcopy with coaxial catheter. For more details, refer to the 'Sources of evidence' section.\n\nOne Specialist Advisor considered the main potential adverse effect of this procedure to be perforation of the fallopian tube; this is usually a minor complication.\n\n# Other comments\n\nThis is one of a number of techniques for examining the fallopian tubes, but it is seldom used in the UK.\n\nAndrew DillonChief ExecutiveJune 2004", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of falloposcopy with coaxial catheter', November 2002.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': "As part of the NICE's work programme, the current guidance was considered for review but did not meet the review criteria as set out in the IP process guide. This guidance therefore remains current.\n\nJanuary 2012: minor maintenance.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg62
734dc988448476dfb0265d66f8c32cd51fb2668e	nice	Subthalamotomy for Parkinson's disease	Subthalamotomy for Parkinson's disease # Guidance Current evidence on the safety and efficacy of subthalamotomy for Parkinson's disease does not appear adequate to support the use of this procedure without special arrangements for consent and for audit or research. Clinicians wishing to undertake subthalamotomy for Parkinson's disease should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having subthalamotomy for Parkinson's disease. Subthalamotomy for Parkinson's disease is a treatment option in the PD Surg trial, which is expected to complete randomisation in 2005/6. Clinicians are encouraged to consider randomising patients in the trial. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence. It is recommended that patient selection should be made with the involvement of a multidisciplinary team, and that patients should be offered the procedure only when their disease has become refractory to best medical treatment.# The procedure # Indications Parkinson's disease is a chronic disease of the brain characterised by gradually worsening tremor, muscle rigidity, and difficulties with starting and stopping movements. The condition is usually treated with drugs. Surgery may be considered for people who have responded poorly to drugs, who have severe side effects from medication or who have severe fluctuations in response to drugs (on–off syndrome). Parkinson's disease affects about 0.5% of people aged 65 to 74 years and 1–2% of people aged 75 years and older. Experts believe that 1–10% of people with Parkinson's disease might be suitable for brain surgery. Surgery for Parkinson's disease is carried out on structures within the brain that are responsible for the modification of movements, such as the thalamus, the globus pallidus and the subthalamic nucleus. Surgery may be carried out on these structures in either or both hemispheres of the brain. Surgical treatment aims to correct the imbalance created by diminished function of the substantia nigra – the underlying abnormality in Parkinson's disease. Surgery alters, either through destruction or electrical stimulation, the function of brain nuclei (such as the thalamus, globus pallidus or subthalamus) that interact functionally with the substantia nigra. Subthalamotomy is oneform of surgery for Parkinson's disease. # Outline of the procedure Subthalamotomy involves inserting very fine needles into the brain through small holes made in the skull, to destroy a part of the subthalamic nucleus using heat or radiofrequency. The exact points of needle insertion may be different in each patient. The procedure is usually carried out under local anaesthetic. Patients remain awake during the procedure so that the effects on movements can be monitored. # Efficacy The evidence was limited to small case series, with only two case series assessing efficacy on a total of 32 patients. Both these studies suggested an improvement in motor skills as measured by the Unified Parkinson Disease Rating Scale (UPDRS) at 12 months' follow-up. For more details, refer to the Sources of evidence. The Specialist Advisors commented that there were not enough data to assess the long-term benefits of subthalamotomy for Parkinson's disease, and that subthalamic electrical stimulation had become the preferred intervention. # Safety Reported complications included persistent dyskinesia, deterioration in learning and retrieval, and deterioration in spatial working memory. In one study of 66 patients, signs of cerebellar dysfunction persisted in 41% (27/66) of patients 2 weeks after surgery. For more details, refer to the Sources of evidence. The Specialist Advisors listed the potential complications as risk of stroke; hemiballismus; and disturbance of speech, swallowing or gait. One Advisor was concerned about the irreversible nature of subthalamotomy and the potential need for repeated surgery. # Other comments Current evidence relates to relatively young patients.# Further information The Institute has produced guidance on deep brain stimulation for Parkinson's disease. The Institute is also in the process of producing clinical guideline on Parkinson's disease, which is due to be published in March 2006 . Andrew DillonChief ExecutiveJune 2004 # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of subthalamotomy for Parkinson's disease does not appear adequate to support the use of this procedure without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake subthalamotomy for Parkinson's disease should take the following actions.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having subthalamotomy for Parkinson's disease.\n\nSubthalamotomy for Parkinson's disease is a treatment option in the PD Surg trial, which is expected to complete randomisation in 2005/6. Clinicians are encouraged to consider randomising patients in the trial.\n\nPublication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.\n\nIt is recommended that patient selection should be made with the involvement of a multidisciplinary team, and that patients should be offered the procedure only when their disease has become refractory to best medical treatment.", 'The procedure': "# Indications\n\nParkinson's disease is a chronic disease of the brain characterised by gradually worsening tremor, muscle rigidity, and difficulties with starting and stopping movements. The condition is usually treated with drugs. Surgery may be considered for people who have responded poorly to drugs, who have severe side effects from medication or who have severe fluctuations in response to drugs (on–off syndrome).\n\nParkinson's disease affects about 0.5% of people aged 65 to 74 years and 1–2% of people aged 75 years and older. Experts believe that 1–10% of people with Parkinson's disease might be suitable for brain surgery.\n\nSurgery for Parkinson's disease is carried out on structures within the brain that are responsible for the modification of movements, such as the thalamus, the globus pallidus and the subthalamic nucleus. Surgery may be carried out on these structures in either or both hemispheres of the brain.\n\nSurgical treatment aims to correct the imbalance created by diminished function of the substantia nigra – the underlying abnormality in Parkinson's disease. Surgery alters, either through destruction or electrical stimulation, the function of brain nuclei (such as the thalamus, globus pallidus or subthalamus) that interact functionally with the substantia nigra. Subthalamotomy is oneform of surgery for Parkinson's disease.\n\n# Outline of the procedure\n\nSubthalamotomy involves inserting very fine needles into the brain through small holes made in the skull, to destroy a part of the subthalamic nucleus using heat or radiofrequency. The exact points of needle insertion may be different in each patient. The procedure is usually carried out under local anaesthetic. Patients remain awake during the procedure so that the effects on movements can be monitored.\n\n# Efficacy\n\nThe evidence was limited to small case series, with only two case series assessing efficacy on a total of 32 patients. Both these studies suggested an improvement in motor skills as measured by the Unified Parkinson Disease Rating Scale (UPDRS) at 12 months' follow-up. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors commented that there were not enough data to assess the long-term benefits of subthalamotomy for Parkinson's disease, and that subthalamic electrical stimulation had become the preferred intervention.\n\n# Safety\n\nReported complications included persistent dyskinesia, deterioration in learning and retrieval, and deterioration in spatial working memory. In one study of 66 patients, signs of cerebellar dysfunction persisted in 41% (27/66) of patients 2 weeks after surgery. For more details, refer to the Sources of evidence.\n\nThe Specialist Advisors listed the potential complications as risk of stroke; hemiballismus; and disturbance of speech, swallowing or gait. One Advisor was concerned about the irreversible nature of subthalamotomy and the potential need for repeated surgery.\n\n# Other comments\n\nCurrent evidence relates to relatively young patients.", 'Further information': "The Institute has produced guidance on deep brain stimulation for Parkinson's disease. The Institute is also in the process of producing clinical guideline on Parkinson's disease, which is due to be published in March 2006 [Now published as 'Parkinson's disease: diagnosis and management in primary and secondary care'].\n\nAndrew DillonChief ExecutiveJune 2004\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg65
03a4c9896f55197bc8b2aa99ecb42a89a252efe7	nice	Laparoscopic live donor simple nephrectomy	Laparoscopic live donor simple nephrectomy # Guidance Current evidence on the safety and efficacy of laparoscopic live donor simple nephrectomy appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.# The procedure # Indications Kidneys from live donors are considered more likely to be successful in treating endstage renal disease than those from cadaver donors. The standard technique for retrieving kidneys from live donors is by open surgery. The aim of laparoscopic nephrectomy is to reduce donor morbidity and make the process more appealing to potential donors. It can be performed via a transperitoneal or retroperitoneal approach. The transperitoneal approach is preferred because it allows more laparoscopic working space, it makes it easier to remove the kidney and the incision is less painful. # Outline of the procedure The procedure involves the insertion of laparoscopic instruments through the abdominal wall via small incisions, insufflation of carbon dioxide and removal of a kidney. # Efficacy One systematic review and several non-randomised comparative studies were identified. The systematic review found no statistically significant difference between the laparoscopic and open procedures for graft function, graft survival and recipient survival, although there was a lack of long-term follow-up data. One study found recipient acute rejection in the first month to be 30% (33/110) for the laparoscopic procedure and 31% (15/48) for the open procedure. Donor hospital stay was generally shorter for the laparoscopic procedure; means ranged from 1.3 to 3.2 days for the laparoscopic procedure and 4.1 to 4.4 days for the open procedure. Laparoscopic donors generally returned to work earlier than donors undergoing the open procedure; means ranged from 2.1 to 3.9 weeks for the laparoscopic procedure and 4.1 to 7.4 weeks for the open procedure. For more details, refer to the sources of evidence (see below). The Specialist Advisors did not raise any concerns regarding the efficacy of this procedure. # Safety The risks of laparoscopic live donor simple nephrectomy appeared similar to those of open live donor nephrectomy. In a systematic review, donor complication rates were reported to be between 0% (0/20) and 35% (23/65) for open procedures, and between 5% (1/19) and 20% (6/30) for laparoscopic procedures; some studies did not report their open nephrectomy results for comparison. Recipient complications also appeared to be similar for both open and laparoscopic procedures, but these were reported even less often than the donor complications. In a systematic review, recipient ureteric complication rates were reported to be 3–6% for open procedures and 3–10% for laparoscopic procedures. For more details, refer to the sources of evidence (see below). The Specialist Advisors considered the main safety concerns to be bleeding, injury to nearby organs and conversion to open surgery. Andrew DillonChief ExecutiveMay 2004# Further information # Information for the public The Institute has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind. # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of laparoscopic live donor simple nephrectomy', November 2002.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. It has been incorporated into the NICE pathway on chronic kidney disease, along with other related guidance and products. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Changes since publication January 2012: minor maintenance. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': 'Current evidence on the safety and efficacy of laparoscopic live donor simple nephrectomy appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance.', 'The procedure': '# Indications\n\nKidneys from live donors are considered more likely to be successful in treating endstage renal disease than those from cadaver donors.\n\nThe standard technique for retrieving kidneys from live donors is by open surgery. The aim of laparoscopic nephrectomy is to reduce donor morbidity and make the process more appealing to potential donors. It can be performed via a transperitoneal or retroperitoneal approach. The transperitoneal approach is preferred because it allows more laparoscopic working space, it makes it easier to remove the kidney and the incision is less painful.\n\n# Outline of the procedure\n\nThe procedure involves the insertion of laparoscopic instruments through the abdominal wall via small incisions, insufflation of carbon dioxide and removal of a kidney.\n\n# Efficacy\n\nOne systematic review and several non-randomised comparative studies were identified. The systematic review found no statistically significant difference between the laparoscopic and open procedures for graft function, graft survival and recipient survival, although there was a lack of long-term follow-up data. One study found recipient acute rejection in the first month to be 30% (33/110) for the laparoscopic procedure and 31% (15/48) for the open procedure. Donor hospital stay was generally shorter for the laparoscopic procedure; means ranged from 1.3 to 3.2 days for the laparoscopic procedure and 4.1 to 4.4 days for the open procedure. Laparoscopic donors generally returned to work earlier than donors undergoing the open procedure; means ranged from 2.1 to 3.9 weeks for the laparoscopic procedure and 4.1 to 7.4 weeks for the open procedure. For more details, refer to the sources of evidence (see below).\n\nThe Specialist Advisors did not raise any concerns regarding the efficacy of this procedure.\n\n# Safety\n\nThe risks of laparoscopic live donor simple nephrectomy appeared similar to those of open live donor nephrectomy. In a systematic review, donor complication rates were reported to be between 0% (0/20) and 35% (23/65) for open procedures, and between 5% (1/19) and 20% (6/30) for laparoscopic procedures; some studies did not report their open nephrectomy results for comparison. Recipient complications also appeared to be similar for both open and laparoscopic procedures, but these were reported even less often than the donor complications. In a systematic review, recipient ureteric complication rates were reported to be 3–6% for open procedures and 3–10% for laparoscopic procedures. For more details, refer to the sources of evidence (see below).\n\nThe Specialist Advisors considered the main safety concerns to be bleeding, injury to nearby organs and conversion to open surgery.\n\nAndrew DillonChief ExecutiveMay 2004', 'Further information': "# Information for the public\n\nThe Institute has produced information describing its guidance on this procedure for patients, carers and those with a wider interest in healthcare. It explains the nature of the procedure and the decision made, and has been written with patient consent in mind.\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of laparoscopic live donor simple nephrectomy', November 2002.", 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nIt has been incorporated into the NICE pathway on chronic kidney disease, along with other related guidance and products.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nChanges since publication\n\nJanuary 2012: minor maintenance.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg57
db83d23ac8f933711cf427ea009f4a27d7960786	nice	Transpupillary thermotherapy for age-related macular degeneration	Transpupillary thermotherapy for age-related macular degeneration # Guidance Current evidence on the safety and efficacy of transpupillary thermotherapy for age-related macular degeneration does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake transpupillary thermotherapy for age-related macular degeneration should take the following action. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having transpupillary thermotherapy for age-related macular degeneration. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Age-related macular degeneration (AMD) is characterised by damage to the central part of the retina (the macula) resulting in progressive loss of central vision. Peripheral vision is not affected so individuals retain some useful vision. The prevalence of macular degeneration increases with age. Ninety percent of people with AMD have dry (atrophic) macular degeneration, characterised by thinning of the macular retina. The other 10% have wet (exudative or neovascular) macular degeneration, characterised by the growth of abnormal new blood vessels in the choroid layer underneath the retina. These new vessels can leak fluid and cause scarring, which can threaten vision. They can be classified using fluoroscein angiography into 'classic' if they can be seen clearly and 'occult' if they cannot. Wet macular degeneration usually occurs in people who already have dry macular degeneration. Of these two conditions, wet macular degeneration progresses more quickly and vision loss is more severe. Laser therapy is used to coagulate new vessels in wet macular degeneration. However, the procedure itself may permanently impair vision, especially if the vessels are very close to the fovea (subfoveal vessels). Recurrence is common. Laser therapy appears to work only in people with classic neovascular macular degeneration. Other new treatments for macular degeneration include surgery to remove new vessels, radiotherapy, photodynamic therapy, and new drugs that suppress new vessel formation (antiangiogenic drugs). # Outline of the procedure Transpupillary thermotherapy uses laser energy to coagulate vessels in wet macular degeneration and is intended to alter the progression of the disease and to preserve vision. This procedure uses a lower-power, more diffuse beam than standard laser treatment. It may be used to treat patients with occult new vessels. # Efficacy All studies identified were uncontrolled and relatively small with a mean follow-up of no greater than 10 months. The majority of patients in the studies had occult or predominantly occult subfoveal new vessels. Visual acuity improved in 0% (0/12) to 32% (9/28) of eyes and deteriorated in 9% (5/57) to 43% (12/28) of eyes in the studies identified. For more details, refer to the 'Sources of evidence' section. A Specialist Advisor considered that optimal treatment protocols have yet to be established. # Safety The main safety findings reported in the studies reviewed were: large submacular haemorrhage in the first 2 months, 6% (3/49 patients); postoperative haemorrhage, 5% (3/66 eyes); and macular infarction, 1% (1/77 patients). For more details, refer to the 'Sources of evidence' section. The Specialist Advisors considered there to be a risk of unwanted thermal damage to the retina and pigment epithelium.# Further information The Committee will wait for the results of the current randomised controlled trial (TTT4CNV, co-ordinated at the New England Eye Centre, Tufts University School of Medicine, USA) and reconsider the procedure following its publication. Andrew DillonChief ExecutiveMay 2004 # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of transpupillary thermotherapy for age-related macular degeneration', December 2002. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication The guidance was considered for reassessment in June 2007 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of transpupillary thermotherapy for age-related macular degeneration does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake transpupillary thermotherapy for age-related macular degeneration should take the following action.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having transpupillary thermotherapy for age-related macular degeneration.\n\nPublication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nAge-related macular degeneration (AMD) is characterised by damage to the central part of the retina (the macula) resulting in progressive loss of central vision. Peripheral vision is not affected so individuals retain some useful vision. The prevalence of macular degeneration increases with age.\n\nNinety percent of people with AMD have dry (atrophic) macular degeneration, characterised by thinning of the macular retina. The other 10% have wet (exudative or neovascular) macular degeneration, characterised by the growth of abnormal new blood vessels in the choroid layer underneath the retina. These new vessels can leak fluid and cause scarring, which can threaten vision. They can be classified using fluoroscein angiography into 'classic' if they can be seen clearly and 'occult' if they cannot. Wet macular degeneration usually occurs in people who already have dry macular degeneration. Of these two conditions, wet macular degeneration progresses more quickly and vision loss is more severe.\n\nLaser therapy is used to coagulate new vessels in wet macular degeneration. However, the procedure itself may permanently impair vision, especially if the vessels are very close to the fovea (subfoveal vessels). Recurrence is common. Laser therapy appears to work only in people with classic neovascular macular degeneration.\n\nOther new treatments for macular degeneration include surgery to remove new vessels, radiotherapy, photodynamic therapy, and new drugs that suppress new vessel formation (antiangiogenic drugs).\n\n# Outline of the procedure\n\nTranspupillary thermotherapy uses laser energy to coagulate vessels in wet macular degeneration and is intended to alter the progression of the disease and to preserve vision. This procedure uses a lower-power, more diffuse beam than standard laser treatment. It may be used to treat patients with occult new vessels.\n\n# Efficacy\n\nAll studies identified were uncontrolled and relatively small with a mean follow-up of no greater than 10 months. The majority of patients in the studies had occult or predominantly occult subfoveal new vessels. Visual acuity improved in 0% (0/12) to 32% (9/28) of eyes and deteriorated in 9% (5/57) to 43% (12/28) of eyes in the studies identified. For more details, refer to the 'Sources of evidence' section.\n\nA Specialist Advisor considered that optimal treatment protocols have yet to be established.\n\n# Safety\n\nThe main safety findings reported in the studies reviewed were: large submacular haemorrhage in the first 2 months, 6% (3/49 patients); postoperative haemorrhage, 5% (3/66 eyes); and macular infarction, 1% (1/77 patients). For more details, refer to the 'Sources of evidence' section.\n\nThe Specialist Advisors considered there to be a risk of unwanted thermal damage to the retina and pigment epithelium.", 'Further information': "The Committee will wait for the results of the current randomised controlled trial (TTT4CNV, co-ordinated at the New England Eye Centre, Tufts University School of Medicine, USA) and reconsider the procedure following its publication.\n\nAndrew DillonChief ExecutiveMay 2004\n\n# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of transpupillary thermotherapy for age-related macular degeneration', December 2002.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': 'The guidance was considered for reassessment in June 2007 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg58
131caf67607a64adf38b986e18fb1e229c3ed83d	nice	Percutaneous endoscopic laser thoracic discectomy	Percutaneous endoscopic laser thoracic discectomy # Guidance Current evidence on the safety and efficacy of percutaneous endoscopic laser thoracic discectomy does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. Clinicians wishing to undertake percutaneous endoscopic laser thoracic discectomy should take the following action. Inform the clinical governance leads in their Trusts. Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended. Audit and review clinical outcomes of all patients having percutaneous endoscopic laser thoracic discectomy. Further research will be useful in reducing the current uncertainty and clinicians are encouraged to collect longer-term follow-up data. The Institute may review the procedure upon publication of further evidence.# The procedure # Indications Percutaneous endoscopic laser thoracic discectomy is used to treat symptomatic thoracic disc herniation. This occurs when a portion of the intervertebral disc protrudes into the spinal canal and impinges on a nerve root. Symptoms include back pain, radicular pain, nondermatomal leg pain, bladder dysfunction and lower extremity weakness. If left untreated, serious neurological sequelae may occur. Standard discectomy for thoracic disc herniation may be either by open posterolateral or anterior approaches. A percutaneous endoscopic approach may lessen the morbidity associated with the procedure by allowing access and visualisation of the anterior and lateral aspects of the disc. The choice of approach will depend upon the characteristics of the disc herniation and the surgeon's experience with the above techniques. # Outline of the procedure Percutaneous endoscopic laser thoracic discectomy is usually done under local anaesthesia through a small incision in the back, using X-ray monitoring. A needle is introduced into the centre of the affected intervertebral disc. A guidewire is passed through the needle, followed by small instruments, which are used to remove some disc material. A Holmium–YAG laser is then introduced and laser energy is used to destroy more of the disc. Debris is removed by surgical instruments. The patient's neurological status is monitored throughout. # Efficacy No controlled studies were identified. The studies identified provided little detail of study design and outcomes. In one study 96% (96/100) of patients reported 'good-to-excellent results/symptomatic relief', but the meaning of this was not defined. The average time to return to work in this study was 10 days. For more details, refer to the 'Sources of evidence' section. One Specialist Advisor commented that there was no evidence to support the efficacy of the procedure, and that the procedure was difficult to master. # Safety No operative or postoperative complications were reported in the studies identified. However, these studies provided little detail of study design and outcomes. One Specialist Advisor considered that this procedure had the potential for serious neurological complications, and was concerned about risks to patients while surgeons learnt the procedure. This Advisor also thought that the procedure could result in nerve injury. # Other comments This decision relates to the procedure when used in isolation (for example, to treat degenerative disc disease). No judgement is made regarding the use of this procedure as part of a larger operation, such as the treatment of scoliosis. Appropriate patient selection for this procedure is important and may be difficult. Andrew DillonChief ExecutiveMay 2004# Further information # Sources of evidence The evidence considered by the Interventional Procedures Advisory Committee is described in the following document. 'Interventional procedure overview of percutaneous endoscopic laser thoracic discectomy', October 2002. # Information for patients NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# Changes since publication The guidance was considered for reassessment in October 2009 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us. January 2012: minor maintenance.# About this guidance NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland. This guidance was developed using the NICE interventional procedure guidance process. We have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available. Your responsibility This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright © National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT www.nice.org.uk nice@nice.org.uk	{'Guidance': "Current evidence on the safety and efficacy of percutaneous endoscopic laser thoracic discectomy does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.\n\nClinicians wishing to undertake percutaneous endoscopic laser thoracic discectomy should take the following action.\n\nInform the clinical governance leads in their Trusts.\n\nEnsure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's information for the public is recommended.\n\nAudit and review clinical outcomes of all patients having percutaneous endoscopic laser thoracic discectomy.\n\nFurther research will be useful in reducing the current uncertainty and clinicians are encouraged to collect longer-term follow-up data. The Institute may review the procedure upon publication of further evidence.", 'The procedure': "# Indications\n\nPercutaneous endoscopic laser thoracic discectomy is used to treat symptomatic thoracic disc herniation. This occurs when a portion of the intervertebral disc protrudes into the spinal canal and impinges on a nerve root. Symptoms include back pain, radicular pain, nondermatomal leg pain, bladder dysfunction and lower extremity weakness. If left untreated, serious neurological sequelae may occur.\n\nStandard discectomy for thoracic disc herniation may be either by open posterolateral or anterior approaches. A percutaneous endoscopic approach may lessen the morbidity associated with the procedure by allowing access and visualisation of the anterior and lateral aspects of the disc. The choice of approach will depend upon the characteristics of the disc herniation and the surgeon's experience with the above techniques.\n\n# Outline of the procedure\n\nPercutaneous endoscopic laser thoracic discectomy is usually done under local anaesthesia through a small incision in the back, using X-ray monitoring. A needle is introduced into the centre of the affected intervertebral disc. A guidewire is passed through the needle, followed by small instruments, which are used to remove some disc material. A Holmium–YAG laser is then introduced and laser energy is used to destroy more of the disc. Debris is removed by surgical instruments. The patient's neurological status is monitored throughout.\n\n# Efficacy\n\nNo controlled studies were identified. The studies identified provided little detail of study design and outcomes. In one study 96% (96/100) of patients reported 'good-to-excellent results/symptomatic relief', but the meaning of this was not defined. The average time to return to work in this study was 10 days. For more details, refer to the 'Sources of evidence' section.\n\nOne Specialist Advisor commented that there was no evidence to support the efficacy of the procedure, and that the procedure was difficult to master.\n\n# Safety\n\nNo operative or postoperative complications were reported in the studies identified. However, these studies provided little detail of study design and outcomes.\n\nOne Specialist Advisor considered that this procedure had the potential for serious neurological complications, and was concerned about risks to patients while surgeons learnt the procedure. This Advisor also thought that the procedure could result in nerve injury.\n\n# Other comments\n\nThis decision relates to the procedure when used in isolation (for example, to treat degenerative disc disease). No judgement is made regarding the use of this procedure as part of a larger operation, such as the treatment of scoliosis.\n\nAppropriate patient selection for this procedure is important and may be difficult.\n\nAndrew DillonChief ExecutiveMay 2004", 'Further information': "# Sources of evidence\n\nThe evidence considered by the Interventional Procedures Advisory Committee is described in the following document.\n\n'Interventional procedure overview of percutaneous endoscopic laser thoracic discectomy', October 2002.\n\n# Information for patients\n\nNICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.", 'Changes since publication': 'The guidance was considered for reassessment in October 2009 and it was concluded that NICE will not be updating this guidance at this stage. However, if you believe there is new evidence which should warrant a review of our guidance, please contact us.\n\nJanuary 2012: minor maintenance.', 'About this guidance': 'NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.\n\nThis guidance was developed using the NICE interventional procedure guidance process.\n\nWe have produced a summary of this guidance for patients and carers. Information about the evidence it is based on is also available.\n\nYour responsibility\n\nThis guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.\n\nImplementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.\n\nCopyright\n\n© National Institute for Health and Clinical Excellence 2004. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.\n\nContact NICE\n\nNational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT\n\nwww.nice.org.uk\n \n nice@nice.org.uk\n 0845 033 7780'}	https://www.nice.org.uk/guidance/ipg61

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