New search performed and critically appraised; no new evidence selected for inclusion.

New evidence; conclusions changed for:

• CBT versus drug treatments Existing evidence re-evaluated, and reporting in benefits section further enhanced with additional detail. Existing categorisation changed. 'CBT versus antidepressants (unclear which more effective, but weak evidence that effects of CBT may last longer than those of antidepressants)' categorised as Unknown effectiveness.
• CBT plus drug treatments versus drugs alone One systematic review (search date 2005) added which includes a meta-analysis for short- and long-term results.Benefits and harms data enhanced. Categorisation changed. CBT plus antidepressants categorised as Likely to be beneficial compared with antidepressants alone as combination treatment may be more effective.

New evidence; conclusion confirmed for:

• CBT versus other psychological treatments One RCT (73 people) added comparing CBT, exposure in vivo, and waiting list control.It found no significant difference between CBT and exposure in vivo for a range of outcomes. One small RCT (49 people) added comparing CBT versus a self-help method supplied over the internet.The RCT found no significant difference between groups for a range of outcome measures. Categorisation unchanged (Unknown effectiveness) as it is unclear how CBT compares with other psychological treatments.
• Applied relaxation One small RCT (49 people) added comparing applied relaxation therapy versus panic-focused psychodynamic psychotherapy.It found that panic-focused psychodynamic psychotherapy increased response compared with applied relaxation. Categorisation of 'applied relaxation' unchanged (Likely to be beneficial).
• Exposure (external or interoceptive) One RCT added (73 people) comparing exposure in vivo, CBT, and waiting list control.It found no significant difference between exposure in vivo and CBT for a range of outcomes. Categorisation of 'Exposure (external or interoceptive)' unchanged (Likely to be beneficial).
• Self-help One small RCT added (49 people) which compared a self-help method supplied over the internet versus CBT given in person.The RCT found no significant difference between groups for a range of outcome measures. Categorisation of 'self-help (may be as effective as other forms of CBT)' unchanged (Likely to be beneficial).
• Brief dynamic psychotherapy One small RCT (49 people) added comparing panic-focused psychodynamic psychotherapy versus applied relaxation therapy.It found that panic-focused psychodynamic psychotherapy increased response compared with applied relaxation. Categorisation of 'Brief dynamic psychotherapy' unchanged (Unknown effectiveness).
• Benzodiazepines One systematic review (search date 2006) added which compared alprazolam versus placebo, and found that alprazolam significantly increased the proportion of people free from panic attacks compared with placebo.Categorisation of benzodiazepines unchanged (Trade-off between benefits and harms).
• CBT plus drug treatments versus CBT alone One systematic review (search date 2005) added incuding a meta-analysis for short- and long-term outcomes. Benefits and harms data enhanced. Categorisation of 'CBT plus antidepressants versus CBT alone (combination may be more effective in acute phase; unclear which is more effective with continued treatment, or 6–24 months after treatment discontinuation)' unchanged (Likely to be beneficial).

New evidence; conclusions changed for:

• Tretinoin One RCT added comparing tretinoin versus placebo cream in people with sun-damaged skin. It found that tretinoin increased the proportion of people with improved fine wrinkles at 6 months compared with placebo, but also increased skin erythema, peeling, burning, dryness, and itching. Categorisation changed (Trade-off between benefits and harms).

New evidence; conclusion confirmed for:

• Controlled cord traction One systematic review added comparing controlled cord traction alone versus minimal intervention in third stage labour. The review included two quasi-randomised trials with conflicting results, no conclusions were reported due to serious methodological flaws of the original data. Categorisation unchanged (Likely to be beneficial).
• Uterine massage One RCT added comparing unterine massage plus active managment versus active managment alone. It found that uterine massage reduced blood loss at 30 and 60 minutes post delivery, and reduced the need for additional uterotonic agent compared with active management. However there was no signficant difference between groups in rates of postpartum haemorrhage. Categorisation changed from Unknown effectiveness to Likely to be beneficial (based on consensus).
• Oxytocin One RCT added comparing oxytocin (5 IU at time of delivery) versus no oxytocin. All women received immediate cord clamping and controlled cord traction. The RCT found that: postpartum anaemia was less frequent among women administered oxytocin; that oxytocin improved haemoglobin drop; and that the third stage labour was shorter with oxytocin than with no oxytocin. Categorisation unchanged (Beneficial).
• Carboprost injection One systematic review and one additional RCT added comparing carboprost versus methylergometrine. The systematic review included two RCTs and reported them separately. The first RCT included in the review reported no instances of postpartum haemorrhage for either intervention. The second RCT included in the review reported that carboprost decreased blood loss in the third and fourth stages of labour, but found no significant difference for postpartum haemorrhage compared with methylergometrine. The additional RCT found no significant difference for postpartum haemorrhage or blood loss for carboprost compared with methylergometrine, but found that methylergometrine reduced duration of third stage labour compared with carboprost. Categorisation unchanged (Trade-off between benefits and harms).
• Ergot compounds One systematic review added comparing ergot compounds versus placebo/no treatment. The review found that ergot compounds decrease the risk of postpartum haemorrhage, mean blood loss, and additional uterotonic administration, but found no significant difference in the risk of retained placenta or blood transfusion compared with placebo or no treatment. The review also reported that ergot administration increased the risk of vomiting, elevated blood pressure, and pain after birth requiring pain medication. Categorisation unchanged (Trade-off between benefits and harms).
• Misoprostol (sublingual) One systematic review added comparing sublingual misoprostol versus oxytocin or ergotomine. The systematic review found no significant difference between sublingual misoprostol and oxytocin for blood loss of at least 500 mL or blood loss of at least 1000 mL. The review reported no significant difference between sublingual misoprostol versus methylergonovine for blood loss of at least 500 mL or blood loss of at least 1000 mL, the review also found no significant difference in mean total blood loss for sublingual misoprostol versus methylergotomine. Categorisation unchanged (Unknown effectiveness).
• Misoprostol (oral) One systematic review and two additional RCTs added comparing oral misoprostol versus placebo/no intervention, or ergot compounds, or oxytocin, or oxytocin plus ergot compounds. Most of the new evidence found no significant difference between oral misoprostol versus any of the comparison groups for maternal death, severe postpartum haemorrhage (at least 1000 mL), postpartum haemorrhage (at least 500 mL), use of additional uterotonics, blood transfusions, and a manual removal of the placenta. The new evidence also reported that oral misoprostol increased the risk of some adverse effects including, nausea, vomiting, shivering, fever, headache, and diarrhoea. Categorisation unchanged (Likely to be ineffective or harmful).
• Misoprostol (rectal) One systematic review added comparing rectal misoprostol versus oxytocin, oxytocin plus ergometrine, or carboprost injections. The review found no differences between rectal misoprostol versus oxytocin for maternal death, severe postpartum haemorrhage (at least 1000 mL), postpartum haemorrhage (at least 500 mL), manual removal of the placenta, or blood transfusions. One of the RCTs included in the review found that rectal misoprostol increased the use of additional uterotonics versus oxytocin. No differences were found for rectal misoprostol versus oxytocin plus ergometrine for postpartum haemorrhage (at least 500 mL), but the review found that rectal misoprostol increased the risk of severe postpartum haemorrhage (at least 1000 mL), the use of additional uterotonics, and blood transfusions, compared with oxytocin plus ergometrine. The review found no differences between rectal misoprostol versus carboprost injection for postpartum haemorrhage (at least 500 mL), but found that rectal misoprostol increased the use of additional uterotonics. The review also reported that rectal misoprostol increased the risk of shivering and fever. Categoristion unchanged (Likely to be ineffective or harmful).

New evidence; conclusions changed for:

• Anticholinergics versus beta₂ agonists Five systematic reviews updated that found no significant differences between various anticholinergics and beta₂ agonists for the majority of outcomes. One review reported that ipratropium led to small improvements in the dyspnoea, fatigue, emotion, and mastery components of the Chronic Respiratory Disease Questionnaire compared with salmeterol. One review found that tiotropium led to a larger improvement in FEV₁ compared with salmeterol. Categorisation of anticholinergics versus beta₂ agonists changed from Likely to be beneficial to Unknown effectiveness as both treatments are effective, and it is unclear if one is consistently more effective than the other.
• Corticosteroids (inhaled) One review added that found that inhaled corticosteroids reduced COPD exacerbations compared with placebo at a mean follow-up of 20 months. However, the review found no significant difference between groups in mortality. One large RCT added that found no significant difference at 3 years between fluticasone and placebo in all-cause mortality. Benefits of treatment are thought to outweigh adverse effects of long-term treatment. Corticosteroids (inhaled) recategorised from Trade-off between benefits and harms to Beneficial.

New evidence; conclusion confirmed for:

• Anticholinergics One systematic review added. The review found that tiotropium, a long-acting anticholinergic, reduced COPD exacerbation rates at 12–52 weeks and improved FEV₁compared with placebo. Categorisation unchanged (Beneficial).
• Beta₂ agonists (inhaled) One systematic review added that found that long-acting beta₂ agonists improved rates of COPD exacerbation compared with placebo. The review found no significant difference between groups in mortality. One large RCT added that found no significant difference at 3 years in all-cause mortality between salmeterol alone and placebo. Categorisation unchanged (Beneficial).
• Anticholinergics plus beta₂ agonists (inhaled anticholinergics plus beta₂ agonists improved FEV₁ compared with either drug alone) One systematic review added found a small but significant improvement in mean peak FEV₁ response after 85 days treatment with ipratropium plus short-acting beta₂ agonist compared with short-acting beta₂ agonist alone.One systematic review added that found no new evidence on the effects of short-acting anticholinergic plus long-acting inhaled beta₂ agonist compared with beta₂ agonist alone. Categorisation unchanged (Beneficial).
• Theophylline One RCT added that found that, at 12 months, theophylline reduced the frequency and duration of acute COPD exacerbations, and improved FEV₁ compared with placebo. Categorisation unchanged (Trade-off between benefits and harms).
• Corticosteroids plus long-acting beta₂ agonists One large RCT added found lower mortality at 3 years with salmeterol plus fluticasone compared with fluticasone aloneHowever, there was no significant difference between salmeterol plus fluticasone and either placebo or salmeterol alone for this outcome. Categorisation unchanged (Beneficial).
• Mucolytics One systematic review updated that found that mucolytics for 2–36 months reduced the average number of exacerbations and days of disability compared with placebo. However, results should be interpreted with caution as many of the RCTs identified by the review included people with chronic bronchitis rather than COPD. Categorisation unchanged (Unknown effectiveness).
• Oxygen (long-term domiciliary treatment) One review updated, which found lower mortality with long-term oxygen treatment in people with severe hypoxaemia compared with no oxygen treatment at 5 years' follow-up. However, the review found no significant difference in mortality in people with mild to moderate hypoxaemia. Categorisation unchanged (Likely to be beneficial for long-term treatment in people with severe hypoxaemia).
• Pulmonary rehabilitation One RCT added which found that, at 16 weeks, pulmonary rehabilitation led to significant improvements in exercise capacity and dyspnoea symptoms compared with control. Categorisation unchanged (Beneficial).
• Inspiratory muscle training One review added that found no significant difference between IMT and no IMT in inspiratory muscle strength.However, the review pooled data from only two small RCTs for this comparison. The review and a subsequent RCT found that IMT significantly improved inspiratory threshold loading and walking distance test compared with sham IMT. Results for other outcomes assessed differed between the review and the RCT. Categorisation unchanged (Likely to be beneficial).

New evidence; conclusion confirmed for:

• Itraconazole (oral) One RCT added to the benefits section comparing oral pulsed itraconazole versus oral terbinafine. The RCT found no significant difference in cure rates between groups at 48 weeks. One open-label RCT added to the harms section comparing oral itraconazole versus oral terbinfine. It found no significant difference in the rate of relapse between groups. Categorisation unchanged (Beneficial).
• Oral terbinafine One RCT added to the benefits section comparing oral pulsed itraconazole versus oral terbinafine. The RCT found no significant difference in cure rates between groups at 48 weeks. One open-label RCT added to the harms section comparing oral itraconazole versus oral terbinfine. It found no significant difference in the rate of relapse between groups. One open-label RCT added to the harms section comparing amorolfine hydrochloride plus oral terbinafine versus terbinafine alone. It found similar rates of adverse effects in each group. Categorisation unchanged (Beneficial).
• Ciclopirox (topical) One systematic review comparing ciclopirox versus placebo updated. The review found that ciclopirox significantly decreased rates of treatment failure compared with placebo. Categorisation unchanged (Likely to be beneficial).
• Mechanical debridement One open-label study added. Harms data enhanced, categorisation unchanged (Unknown effectiveness).
• Amorolfine (topical) One systematic review updated, no new data added. One open-label RCT added to the harms section comparing amorolfine hydrochloride 5% nail lacquer plus oral terbinafine versus oral terbinafine alone. It found similar rates of adverse effects in each group. Categorisation unchanged (Unknown effectiveness).
• Butenafine (topical) One systemtaic review updated, no new data added. Categorisation unchanged (Unknown effectiveness).
• Fluconazole (topical) One systematic review updated, no new data added. Categorisation unchanged (Unknown effectiveness).
• Ketoconazole (topical) One systematic review updated, no new data added. Categorisation unchanged (Unknown effectiveness).
• Terbinafine (topical) One systematic review updated, no new data added. Categorisation unchanged (Unknown effectiveness).
• Tioconazole (topical) One systematic review updated, no new data added. Categorisation unchanged (Unknown effectiveness).

New evidence; conclusions changed for:

• Nurse-led management

New evidence; conclusion confirmed for:

• Paroxetine: One systematic review on the increased risk of suicidal behaviour associated with SSRIs added to the harms section. The review found that SSRIs increased the risk of suicide attempts compared with placebo but not compared with tricyclic antidepressants. Categorisation unchanged (Unknown effectiveness).
• Telephone contact : One RCT added. The RCT found that telephone contact at 1 month decreased the proportion of people repeating self-harm at 6 months compared with treatment as usual. However, there was no significant difference between the two groups at 13 months. The RCT also found no significant difference between telephone contact at 3 months and usual care at either 6 or 13 months' follow-up. However, at 13 months, 48 of the 103 suicide attempts occured before telephone contact at 1 month. Categorisation unchanged (Unknown effectiveness).

New evidence; conclusion confirmed for:

• Pancreatic enzyme supplements One RCT added which found that pancreatic enzyme supplements caused a greater reduction in faecal fat from baseline to 2 weeks, compared with placebo. It found no significant difference in overall symptom relief between groups. Categorisation unchanged (Likely to be beneficial).
• Method of ductal decompression One RCT added which compared endoscopic ductal decompression versus surgical ductal decompression. It found that surgical decompression reduced pain at 2 years. Categorisation unchanged (Trade-off between benefits and harms).

New option(s) added for:

• Percutaneous, followed by early cholecystectomy v medical, followed by delayed cholecystostomy

New evidence; conclusion confirmed for:

• Early v delayed cholecystectomy One systematic review added comparing early versus late cholecystectomy. The review found no difference between groups in the rates of conversion from laparoscopic cholecystectomy to open cholecystectomy. Categorisation unchanged (Beneficial).
• Laparoscopic cholecystectomy One observational study added to the comments section investigating the prevalence of persistent abdominal pain 5 years after cholecystectomy. The study found that neither the duration of symptom history prior to cholecystectomy, indication for cholecystectomy, nor the surgical method made a difference in the prevalence of abdominal pain 5 years after cholecystectomy. Categorisation unchanged (Beneficial).

New search performed and critically appraised; no new evidence selected for inclusion.

New evidence; conclusion confirmed for:

• Colchicine (oral) One updated systematic review added, which identified no new RCTs; categorisation unchanged (Unknown effectiveness).
• Corticosteroids One systematic review added, which identified one RCT; benefits data enhanced; categorisation unchanged (Unknown effectiveness).

New evidence; conclusions changed for:

• NSAIDs Two RCTs comparing NSAIDs against each other added. One RCT found no significant difference between valdecoxib and diclofenac in pain intensity 3 days after initial treatment. The second RCT found a significant improvement in pain intensity after 1–6 days' treatment with lornoxicam compared with diclofenac. However, there was no significant difference between treatments in time to onset of pain relief. Categorisation changed from Beneficial to Trade-off between benefits and harms: use of NSAIDs can be associated with severe adverse effects and evidence is not thought to support favourable treatment effect of NSAIDs for all people with acute low back pain.
• Back exercises One review found evidence that McKenzie treatment may be more effective than passive therapies (such as educational booklets, ice packs, and massage) and flexion exercises at improving pain and disability, but less effective than spinal manipulation or advice to stay active.Another review found no significant difference in short-term disability between McKenzie treatment and the NSAID ketoprofen (follow-up at less than 3 months). One RCT added found no significant difference between graded activity and usual care in pain severity and functional status at 12 months.One RCT added found that neuromuscular training plus CBT improved pain intensity for the 7 days before assessment, but not for the 2 months before assessment, compared with CBT alone. The RCT found no significant difference between treatments in functional status. Categorisation changed (from Unlikely to be beneficial to Unknown effectiveness). For specific exercises, there is a growing but still limited amount of evidence for short-term pain reduction and increased function. Given the methodological flaws associated with RCTs and systematic reviews of back exercises, and the lack of relevant detail of the primary studies, it is not possible to either support or oppose the use of exercise in patients with back pain.

New evidence; conclusion confirmed for:

• Analgesics (paracetamol, opioids) One RCT added that found no significant difference in pain reduction at 10 days between paracetamol plus tramadol and tramadol alone.However, compared with tramadol alone, the combination treatment was associated with significantly fewer adverse effects. Categorisation unchanged (Unknown effectiveness).
• Multidisciplinary treatment programmes One RCT reported in two publications found a small, but significant, worsening in pain intensity at 26 weeks with a multidisciplinary treatment programme compared with usual care. However, there was no significant difference between groups in functional status. At 12 months, the study found no significant difference between a multidisciplinary programme and individual components of the programme and usual care in pain intensity and functional status. Categorisation unchanged (Unknown effectiveness).
• Temperature treatments One systematic review added that found that heat wrap significantly improved pain intensity and functional status compared with placebo, and compared with paracetamol (acetaminophen) and ibuprofen. However, the review did not pool data, the RCTs identified were small, and follow-up was short term. Categorisation unchanged (Unknown effectiveness).
• Traction One systematic review added; harms section enhanced; categorisation unchanged (Unknown effectiveness). The review identified no RCTs on the effectiveness of traction in people with acute low back pain without sciatica.

New option(s) added for:

• Modafinil One RCT added; benefits and harms data added; categorised as Likely to be beneficial. The RCT found that, compared with placebo, once-daily modafinil 300 mg and modafinil 200/100 mg (divided dose) improved symptoms of ADHD at 4 weeks (assessed using various scales). The RCT found no significant difference in changes in ADHD symptoms between modafinil 100/200 mg and placebo on any assessment scale.
• Bupropion Two RCTs (three publications) added; benefits and harms data enhanced; categorised as Unknown effectiveness. Both RCTs found that bupropion improved symptoms of ADHD at 28 days compared with placebo. However, absolute numbers were not available for all comparisons and the second RCT was small in size.
• Omega-3 polyunsaturated fatty acid compounds One systematic review and one RCT added; benefits and harms data added; categorised as Unknown effectiveness. The review identified one RCT of sufficient quality that assessed the effects of taking food supplemented with omega-3 polyunsaturated fatty acid-rich fish oil compared with eating placebo foods containing olive oil.The RCT found no significant difference in severity of symptoms of ADHD between groups at 4 months.
• Homeopathy One systematic review and two RCTs added; benefits and harms data added; categorised as Unknown effectiveness. One RCT identified by the review found that homeopathic treatment improved symptoms of ADHD at 12 weeks compared with placebo (mean difference between groups in Conners Global Index score at 12 weeks. The second RCT identified by the review found no significant difference at 18 weeks in improvement in ADHD symptoms between homeopathic remedies and placebo.
• Dexamfetamine sulphate plus psychological treatment One systematic review and one RCT added; benefits and harms data added; categorised as Unknown effectiveness. The review identified no RCTs of sufficient quality comparing dexamfetamine plus psychological treatment versus placebo. One RCT identified by the review found that slow-release formulation of dexamfetamine plus psychological treatment improved symptoms of ADHD compared with placebo plus psychological treatment.

New evidence; conclusions changed for:

• Clonidine One RCT added; benefits and harms data enhanced; categorisation changed (from Unknown effectiveness to Likely to be beneficial). The RCT found that clonidine improved severity of ADHD symptoms at 16 weeks compared with placebo. The RCT found no significant difference in change of severity of ADHD symptoms between clonidine alone and methylphenidate alone.

New evidence; conclusion confirmed for:

• Atomoxetine Two systematic reviews and two RCTs added; benefits and harms data enhanced; categorisation unchanged (Likely to be beneficial). One review and one RCT found that atomoxetine improved symptoms of ADHD compared with placebo. The second review identified no RCTs that met our inclusion criteria. The second RCT found no significant difference between atomoxetine and methylphenidate in response rate at 8 weeks.
• Dexamfetamine sulphate One systematic review added; benefits and harms data enhanced; categorisation unchanged (Likely to be beneficial). The review found that, for medium-dose dexamfetamine (10–20 mg/day), results for hyperactivity varied with assessment scale used, but that high-dose dexamfetamine (more than 20 mg/day) seemed to improve hyperactivity compared with placebo.
• Methylphenidate One systematic review and six RCTs added; benefits and harms data enhanced; categorisation unchanged (Likely to be beneficial). The review found variable results on the effects of methylphenidate on the symptoms of ADHD compared with placebo. One RCT found that methylphenidate improved severity of ADHD symptoms at 16 weeks compared with placebo. Two RCTs found that transdermal methylphenidate improved symptoms of ADHD compared with placebo at 12 hours. One subsequent RCT found that both extended-release and immediate-release formulations of methylphenidate improved symptoms of ADHD compared with placebo.One RCT found improvements in attention at 12 hours and in attempts at and correct completion of mathematical problems at 8 hours for extended- and modified-release formulations of methylphenidate compared with placebo. One RCT comparing atomoxetine versus methylphenidate found no significant difference between treatments in response rate at 8 weeks.
• Methylphenidate plus psychological/behavioural treatment One systematic review added; benefits data enhanced; categorisation unchanged (Likely to be beneficial). The review reported that methylphenidate plus psychological treatment improved symptoms of ADHD compared with psychological treatment alone.

New option(s) added for:

• Beta-blockers plus other anti-anginal drug treatments v beta-blockers alone One systematic review added which included one RCT that met inclusion criteria. The RCT compared three treatments: atenolol (50 mg twice daily), nifedipine (20 or 40 mg twice daily as tolerated), and atenolol plus nifedipine. It found no difference between the combination of atenolol plus nifedipine and atenolol alone in the combined outcome of mortality, MI, or unstable angina, after a mean follow-up of 2 years. Categorisation based on consensus (Likely to be beneficial).
• Calcium channel blockers plus other anti-anginal drug treatments v calcium channel blockers alone One systematic review added which included one RCT that met Clinical Evidence inclusion criteria. The RCT compared three treatments: nifedipine, atenolol, and atenolol plus nifedipine. It found no difference between the combination of nifedipine plus atenolol versus nifedipine alone in the combined outcome of mortality, MI, or unstable angina, after a mean follow-up of 2 years. Categorisation based on consensus (Likely to be beneficial).
• Nitrates plus other anti-anginal drug treatments versus nitrates alone We found no systematic review or RCTs that met the inclusion criteria for this review. Categorisation based on consensus (Likely to be beneficial).
• Potassium channel openers plus other anti-ishcaemic drug versus potassium channel openers alone We found no systematic review or RCTs that met the inclusion criteria for this review. Categorisation based on consensus (Likely to be beneficial).
• Beta-blockers in addition to existing anti-anginal drug treatment We found no systematic review of RCTs that met Clinical Evidence inclusion criteria. Categorised as Unknown effectiveness.
• Calcium channel blockers in addition to exisiting anti-anginal drug treatment One large RCT identified comparing additional treatment with slow-release nifedipine versus placebo. Over an average of 4.9 years’ follow-up, the RCT found no significant difference between groups in the primary end point of combined death, MI, refractory angina, new overt heart failure, debilitating stroke and peripheral revascularisation. The RCT found that nifedipine reduced the need for coronary angiography and bypass surgery compared with placebo. Categorised as Likely to be beneficial.
• Nitrates in addition to existing anti-anginal drug treatment: We found no systematic review or RCTs that met the inclusion criteria for this revew. Categorisation (Unknown effectiveness).
• Potassium channel openers in addition to existing anti-anginal drug treatments One large RCT identified comparing nicorandil versus placebo. The RCT found nicorandil reduced the rate of the composite primary end point (CHD death, non-fatal MI, or unplanned hospital admission for cardiac chest pain) compared with placebo at an average 1.6 years' follow-up. Categorised as Likely to be beneficial.

New option(s) added for:

• Soy formula with added fibre: New option for which we found one RCT comparing cows' milk formula versus soy formula with added fibre. Categorised as Trade-off between benefits and harms.

New evidence; conclusion confirmed for:

• Metoclopramide One systematic review added comparing metoclopramide versus placebo. The review did not pool data owing to heterogeneity of trials. Individual trials found that metoclopramide improved gastric fractional emptying rates in term and postoperative infants compared with placebo, but found symptom scores and scintigraphy with metoclopramide and placebo. A subgroup analysis in one trial of infants aged less than 3 months found that metoclopramide improved weight gain compared with placebo. Two further RCTs included in the review found similar pH measurements with metoclopramide and placebo. Categorisation unchanged: Trade-off between benefits and harms.
• Surgery : One systematic review added comparing fundoplication versus postoperative medication for GORD in children with neurological impairment undergoing gastrostomy. The review found no RCTs. Categorised unchanged: Unknown effectiveness.

New evidence; conclusions changed for:

• Analgesics (paracetamol, opioids): One systematic review added comparing opioids with placebo and opioids with opioids. Benefits and harms sections enhanced, categorisation changed from Likely to be beneficial to Unknown effectiveness, as the systematic review found no difference in pain reduction between different classes of opioids and placebo or other opioids.
• NSAIDs: One RCT added comparing etoricoxib with diclofenac. The RCT found that etoricoxib did not reduce pain or disability compared with diclofenac at 4-week follow-up. Categorisation changed from Likely to be beneficial to Trade-off between benefits and harms.
• Facet joint injections : One RCT added evaluating sodium hyaluronate and triamcinolone acetonide. Benefits and harms sections enhanced, categorisation changed from Likely to be ineffective or harmful to Unknown effectiveness, as the evidence is inconclusive with no direct comparison being made between treatment groups.
• Spinal mainpulative therapy: One RCT added comparing four groups: chiropractic care without physical modalities, chiropractic care with physical modalities, medical care without physiotherapy, and medical care with physiotherapy. The RCT found no differences between groups for pain, disability, or clinical remission at 18 months. Categorisation changed from Likely to be beneficial to Unknown effectiveness.

New evidence; conclusion confirmed for:

• Back exercises: Five systematic reviews and two subsequent RCTs added, comparing varying forms of generic exercise with no exercise or other exercise programs. The evidence suggests that exercise improves function and decreases pain compared with no exercise in people with chronic low back pain. Specific approaches, such as the McKenzie method and Yoga, improved function compared with conventional exercise. The evidence supports the categorisation of Beneficial.
• Multidisciplinary programmes: One RCT added comparing mulitdisciplinary rehabilitation with individual physiotherapy. The RCT found no differences between groups for pain or disability at 6,12, or 24 months. Categorisation unchanged (Beneficial).
• Acupuncture: One low-quality RCT added comparing acupuncture with no acupuncture. The evidence found that acupuncture increases function and decreases pain compared with no acupuncture in the short term. Categorisation unchanged (Unknown effectiveness).
• Back Schools: One RCT added comparing back school plus medication versus medication only. The RCT did not make direct comparisons between groups, but with baseline scores only. It found that back school improved function and reduced pain at 3-month follow-up compared to baseline. Categorisation unchanged (Likely to be benefical).
• Behavioural therapy : One RCT added comparing CBT with waiting list control. The RCT found that CBT reduced disability and pain at 10 weeks compared with control. Categorisation unchanged (Likely to be beneficial).
• Traction: One systematic review added comparing traction with with placebo or sham treatments. The review did not include RCTs soley on people with chronic lower back pain without sciatica. Categorisation unchanged (Unknown effectiveness).
• TENS: One systematic review added comparing active TENS with placebo. The review did not pool data due to heterogeneity between trials. One small, low-quality RCT included in the review found that active TENS decreased subjective pain intensity compared with placebo. However, the second RCT included in the review found no differences between TENS and placebo for any outcomes measured, including pain relief and functional status.Categorisation unchanged (Unknown effectiveness).

New option(s) added for:

• Nasogastric decompression after abdominal surgery (selective versus routine) One systematic review and three subsequent RCTs added. The review found no significant difference between selective nasogastric decompression and routine nasogastric decompression in postoperative pulmonary complication rates, but rates of infection were lower with selective nasogastric decompression. Selective nasogastric decompression was associated with a non-significant trend toward increased risk of wound infection. The three subsequent RCTs all found a significant decrease in respiratory complications with selective compared with routine nasogastric decompression. However, the RCTs assessed people undergoing different types of surgery. Categorisation set at Likely to be beneficial.

New evidence; conclusions changed for:

• Lung expansion techniques One systematic review added; categorisation changed from Beneficial to Unknown effectiveness. The review found no significant difference between any lung expansion technique versus no intervention for postoperative pneumonia after abdominal surgery and any postoperative infection outcome after cardiac surgery. Evidence now reported does not support a categorisation of Beneficial.

New evidence; conclusion confirmed for:

• Regional (epidural or spinal) anaesthesia One RCT in people having carotid surgery added. The RCT found no significant difference between local and general anaesthesia in rate of pneumonia within 30 days after surgery. However, the number of events may have been too small to detect a clinically important difference between the techniques. Categorisation unchanged (Likely to be beneficial).

New condition.

New option(s) added for:

• Warming hands and feet or keeping warm New option. No systematic reviews, RCTs, or cohort studies identified. 'Warming hands and feet' categorised as 'Unknown effectiveness'.
• Relaxation therapy New option. No systematic reviews, RCTs, or cohort studies identified. 'Relaxation therapy' categorised as 'Unknown effectiveness'.
• Biofeedback New option. No systematic reviews, RCTs, or cohort studies identified. 'Biofeedback' categorised as 'Unknown effectiveness'.
• Smoking cessation New option. No systematic reviews, RCTs, or cohort studies identified. 'Smoking cessation' categorised as 'Unknown effectiveness'.
• Hand exercises New option. No systematic reviews, RCTs, or cohort studies identified. 'Hand exercises' categorised as 'Unknown effectiveness'.
• Glyceryl trinitrate (transdermal) New option. One small crossover RCT (42 people in total, of whom 21 people had secondary Raynaud's phenomenon) included which compares transdermal glyceryl trinitrate versus placebo.'Glyceryl trinitrate (transdermal)' categorised as Unknown effectiveness.
• Calcium channel blockers New option. Three systematic reviews and two RCTs identified. One systematic review which included eight RCTs (109 people with secondary Raynaud's phenomenon (secondary) to systemic sclerosis) pooled data and compared calcium channel blockers versus placebo, and also nifedipine alone versus placebo.'Calcium channel blockers' categorised as Likely to be beneficial.
• Alpha-blockers (oral) New option. Two systematic reviews identified, both of which identified one RCT of sufficient qualitycomparing oral prazosin versus placebo. 'Alpha-blockers' categorised as Unknown effectiveness.
• Naftidrofuryl oxylate New option. No systematic reviews or RCTs identified. 'Naftidrofuryl oxylate' categorised as Unknown effectiveness.
• Moxisylyte New option. No systematic reviews or RCTs identified. 'Moxisylyte' categorised as Unknown effectiveness.
• Inositol nicotinate New option. No systematic reviews or RCTs identified. 'Inositol nicotinate' categorised as Unknown effectiveness.
• ACE inhibitors New option. One systematic review edentified,which identified no RCTs that satisfy Clinical Evidence inclusion criteria, and no subsequent RCTs identified. 'ACE inhibitors' categorised as Unknown effectiveness.
• Angiotensin II receptor antagonists (oral) New option. Three systematic reviews identified, which found no RCTs that satisfied Clinical Evidence inclusion criteria. 'Angiotensin II receptor antagonists' categorised as Unknown effectiveness.
• SRIs New option. No systematic reviews or RCTs that satisfied Clinical Evidence inclusion criteria identified. 'SRIs' categorised as Unknown effectiveness.
• Endothelin-1 receptor antagonists New option. One RCT (122 people with systemic sclerosis and a history of a documented digital ulcer within the previous 12 months) added comparing oral bosentan versus placebo.'Bosentan (an endothelin-1 receptor antagonist) (reduced new digital ulcers compared with placebo in people with systemic sclerosis and previous digital ulceration in the last 12 months; however, no evidence in people with secondary Raynaud's without previous digital ulceration)' categorised as Likely to be beneficial.
• Phosphodiesterase inhibitors New option. One systematic reviewidentified, which found no RCTs that met Clinical Evidence inclusion criteria. One small additional RCT (43 people in total, of whom 21 people has secondary Raynaud's) added,comparing cilostazol versus placebo. 'Phosphodiesterase inhibitors' categorised as Unknown effectiveness.
• Antithrombotics/inhibitors of platelet aggregation New option. No systematic reviews or RCTs identified. 'Antithrombotics/inhibitors of platelet aggregation' categorised as Unknown effectiveness.
• Prostaglandins (oral) New option. One systematic review which includes two RCTs identified, and three subsequent RCTs identified comparing various oral prostaglandins (including oral iloprost, oral cisaprost, and oral beraprost sodium) versus placebo. 'Prostaglandins (oral)' categorised as Unlikely to be beneficial.
• Prostaglandins (intravenous) New option. One systematic review identifiedwhich includes five RCTs comparing intravenous prostaglandins versus placebo, and which pools data. 'Prostaglandins (intravenous)' categorised as beneficial.

New option(s) added for:

• Water birth One systematic review added comparing immersion with no immersion during first and second stage of labour. The review, which identified RCTs of variable methodological quality, found no evidence of benefit or harm for water birth in first or second stage of labour. Catergorisation: Unknown effectiveness.

New evidence; conclusion confirmed for:

• Absorbable sutures in first- and second-degree tears One RCT was added comparing chromic catgut , standard polyglactin 910, and fast-absorbing polyglactin 910 sutures. The RCT found no difference in perineal pain between suture types but found that fast-absorbing polyglactin 910 reduced analgesia use and dyspanuria. Categorisation unchanged (Beneficial).
• Continuous sutures in first- and second-degree tears One RCT added comparing comparing a loose continuous suture for all layers versus interrupted sutures. The RCT found that loose continuous technique for repair of all layers reduced perineal pain at 10 days, supporting the Beneficial categorisaion.
• Different methods and materials for primary repair of obstetric anal sphincter injuries One systematic review added comparing overlap with end-to-end approximation for primary repair of the external anal sphincter after childbirth. The RCT found no difference in perineal pain, faecal urgency or incontinence at 3 months, confirming the categorisation of Unknown effectiveness.

New evidence; conclusion confirmed for:

• Tranexamic acid One RCT added comparing tranexamic acid with medroxyproesterone acetate. There was no direct comparison of menstrual blood loss between groups, but the reduction from baseline was reported for both groups. The RCT found that both treatments reduced menstrual blood loss from baseline at 3 months. Categorisation unchanged (Beneficial).
• Intrauterine progestogens One RCT added comparing progestogen-releasing IUD versus thermal balloon ablation at 12-month follow-up. The RCT found that the progestogen-releasing IUD significantly reduced PBAC scores at 12 months compared with thermal balloon ablation. However, the progestogen-releasing IUD was associated with higher hysterectomy rates at 24 months compared with the thermal balloon. Owing to the small numbers included in the trial, the categorisation remains as Unknown effectiveness.
• Endometrial destruction Two RCTs added comparing either first- with second-generation techniques, or first-generation techniques with each other. The first RCT compared thermal balloon endometrial ablation with transcervical endometrial resection, and found both treatments reduced menstrual blood loss compared with baseline. The second RCT (10-year follow-up of a trial included in the systematic review) compared rollerball ablation and transcervical endometrial resection. The follow-up found no difference between groups for rates of hysterectomy.Categorisation unchanged (Likely to be beneficial).

New evidence; conclusion confirmed for:

• Specialised care One systematic review added;which found a lower rate of death and dependency after stroke with specialised care compared with usual care. Categorisation unchanged (Beneficial).
• Aspirin One RCT added, which found no significant difference in survival rates at 6 months, but fewer haemorrhagic adverse events in the aspirin group compared with the heparin group. Categorisation unchanged (Beneficial).
• Anticoagulants One RCT added, which found no significant difference in survival rates at 6 months, but more haemorrhagic adverse events with heparin compared with aspirin. Categorisation unchanged (Trade-off between benefits and harms).
• Neuroprotective agents One systematic review and one RCT added. The systematic review and RCT found no significant difference in death, dependency, or other poor outcomes between neuroprotective agents and placebo. Categorisation unchanged (Unlikely to be beneficial).
• Blood pressure reduction One RCT added, which found no significant difference between lisinopril and placebo in stroke severity. Categorisation unchanged (Likely to be ineffective or harmful).
• Evacuation One RCT added, which found no significant difference between surgical and nonsurgical management for haematoma in mortality at 1 year. However, surgery improved the level of good functional outcomes compared with non-surgical management. Categorisation unchanged (Unlikely to be beneficial).

New option(s) added for:

• Advice to elevate leg New option for which we found no RCT evidence in people with venous leg ulcers. Categorised as Unknown effectiveness.
• Advice to keep leg active New option for which we found no RCT evidence in people with venous leg ulcers; categorised as Unknown effectiveness.
• Advice to modify diet New option for which we found no RCT evidence in people with venous leg ulcers; categorised as Unknown effectiveness.
• Advice to stop smoking New option for which we found no RCT evidence in people with venous leg ulcers; categorised as Unknown effectiveness.
• Advice to reduce weight New option for which we found no RCT evidence in people with venous leg ulcers; categorised as Unknown effectiveness.

New evidence; conclusion confirmed for:

• Foam or semi occlusive dressings: One systematic review added evaluating the effectiveness of wound dressings to treat venous leg ulcers. The review included two RCTs not previously reported. The first RCT found similar rates of ulcer healing between hyaluronic dressings and paraffin gauze.The second RCT compared a collagen-plus-cellulose dressing versus a modern low-adherent dressing. It found similar healing rates at 12 weeks with both treatments. Categorisation unchanged (Unknown effectiveness).
• Antimicrobial agents (topical) One systematic review added comparing dressings impregnated with silver versus dressings not containing silver for venous ulcers. It found no significant difference between groups in proportion of ulcers completely healed. Categorisation unchanged (Unknown effectiveness).
• Topical negative pressure One RCT added comparing vacuum-assisted closure (VAC) versus conventional wound care techniques. It found that VAC reduced time to complete healing compared with conventional therapy, but did not lengthen time to recurrence. The RCT reported no significant difference in adverse effects between groups, apart from an increased risk of cutaneous damage secondary to therapy in the VAC group. Categorisation unchanged (Unknown effectiveness).
• Occlusive dressings One review and two subsequent RCTs added comparing occlusive dressings with simple dressing in the presence of compression, and other occlusive or semi-occlusive dressings. The review found no significant difference in ulcer healing between hydrocolloid dressings compared with simple low-adherent dressings in the presence of compression, hydrocolloids compared with other modern dressings, or occlusive dressings compared with semi-occlusive dressings. The first subsequent RCT compared a foam dressing with a silicione foam dressing (both under compression) over 24 weeks. It found no significant difference between treatments for complete ulcer healing. The second subsequent crossover RCT compared a foam dressing containing ibuprofen with a similar foam dressing with no ibuprofen. It found that ibuprofen dressings reduced chronic pain on days 1–5 compared with non-ibuprofen dressings, but found no significant difference between groups for ulcer healing at 24 weeks. Categorisation unchanged (Unlikely to be beneficial).
• Pentoxifylline (oral) One systematic review updated comparing pentoxifylline (oxpentifylline) 1200 or 2400 mg daily versus placebo or versus other treatments, with or without compression. It found that, in the presence of compression, pentoxifylline increased the proportion of people with healed ulcers over 8–24 weeks compared with placebo. Categorisation unchanged (Beneficial).
• Sulodexide (oral) One RCT added comparing sulodexide versus compression alone. It found that sulodexide increased healing at 30 days compared with compression alone. Categorisation unchanged (Likely to be beneficial).
• Allogenic single-layer skin replacement One systematic review added comparing single-layer dermal replacement versus usual care. The review found similar rates of healing between 12-piece, 4-piece or 1-piece dermal skin replacement and usual care.
• Skin grafting One systematic review updated, comparing different types of skin grafts. It found insufficient evidence to determine whether skin grafting increased the healing of venous ulcers. Categorisation unchanged (Unknown effectiveness).
• Superficial vein surgery One RCT and one follow-up study added. The RCT compared subfascial endoscopic perforator surgery (SEPS) plus superficial venous surgery as required versus compression alone. It found no significant difference between groups in the number of ulcers healed. The follow-up study compared venous surgery (type of surgery based on duplex scan) plus compression versus compression alone, and found no difference in healing rates between groups at 3 years. Categorisation unchanged (Unknown effectiveness).
• Superficial vein surgery One long-term follow-up study and one RCT added. The long-term follow-up compared superficial vein surgery plus compression versus compression alone, and found that, after 3 years, recurrence rates were lower with surgery plus compression compared with compression alone. One RCT comparing subfascial endoscopic perforating vein surgery (SEPS) plus compression versus compression alone found no significant difference in recurrence rates between groups.Categorisation unchanged (Likely to be beneficial)

New option(s) added for:

• Serotonergic agonists (focal) New option for which we identified no systematic review or RCTs. Categorised as Unknown effectiveness.
• Serotonergic antagonists (focal) New option for which we identified no systematic review or RCTs. Categorised as Unknown effectiveness.
• Serotonergic agonists (generalised) New option for which we identified no systematic review or RCTs. Categorised as Unknown effectiveness.
• Serotonergic antagonists (generalised) New option for which we identified no systematic review or RCTs. Categorised as Unknown effectiveness.

New evidence; conclusion confirmed for:

• Botulinum toxin (focal) One RCT on the effects of botulinum A in treatment of writer's cramp added;benefits and harms data enhanced; categorisation unchanged (Beneficial). At 8 weeks, the RCT found significant improvements in symptom severity, writer's cramp rating scale, handwriting, and speed of writing with botulinum A compared with placebo. However, there was no significant difference between groups at 8 weeks in functional status.
• Deep brain stimulation of thalamus and globus pallidus in focal and generalised dystonia One RCT comparing deep brain stimulation versus sham stimulation added to both focal and generalised dystonia; benefits and harms data enhanced in both interventions; categorisation unchanged (intervention categorised as Unknown effectiveness for both focal and generalised dystonia). The RCT, which included people with primary segmental or generalised dystonia, found that, at 3 months, neurostimulation significantly improved movement and disability scores as assessed on the Burke–Fahn–Marsden Dystonia rating scale, and the physical component of quality of life (assessed using the SF-36 questionnaire), compared with placebo. However, there was no significant difference between groups in the mental component of the SF-36 questionnaire.
• Deep brain stimulation

New option(s) added for:

• Vitamin B supplements (including folate) New option. We found two RCTs comparing vitamin B supplements versus placebo or different regimens versus each other; 'vitamin B supplements (including folate)' categorised as Unknown effectiveness.

New evidence; conclusions changed for:

• Eversion carotid endarterectomy versus conventional carotid endarterectomy One previously reported systematic review updated; benefits and harms data enhanced; 'eversion carotid endarterectomy (no more effective than conventional carotid endarterectomy)' categorised as Unknown effectiveness.

New evidence; conclusion confirmed for:

• Blood pressure reduction One systematic review added, which examined the effects of blood pressure lowering generally in all population groups, not just in those with previous stroke or TIA;benefits and harms data enhanced, categorisation of 'blood pressure reduction' unchanged (Beneficial).
• Cholesterol reduction A new comparison of cholesterol-lowering treatments versus each other added, which identified no systematic reviews or RCTs. One systematic review added to the harms section and one RCT comparing statins versus placebo added to the benefits and harms section;categorisation of 'cholesterol reduction' unchanged (Beneficial).
• Alternative antiplatelet regimens to aspirin One systematic reviewand three RCTs added one of which also included an updated meta-analysis in people with cerebral ischaemia of presumed arterial origin comparing dipryridamole plus aspirin versus aspirin alone. Previous categorisation of alternative antiplatelet regimens to aspirin as Unknown effectiveness changed in light of the additional evidence. "Alternative antiplatelet regimens to aspirin (adding dipyridamole to aspirin shows benefit in reducing composite vascular end points and stroke compared with aspirin alone; no evidence that any other regimen alone has any major advantages over aspirin alone)" categorised as Beneficial.
• Different blood pressure-lowering regimens One systematic review added comparing different antihypertensive drugs; categorisation of 'different blood pressure lowering regimens (no evidence that any regimen is more or less effective than any other)' unchanged (Unknown effectiveness).
• High-dose versus low-dose aspirin One non-systematic review added;harms data enhanced, categorisation of 'high-dose versus low-dose aspirin (no additional benefit but may increase harms)' unchanged (Unlikely to be beneficial).
• Anticoagulation in people in sinus rhythm One already included systematic review updated; no new data added, categorisation of 'anticoagulation in people in sinus rhythm' unchanged (Likely to be ineffective or harmful).
• Carotid endarterectomy in people with less than 30% symptomatic carotid artery stenosis Two systematic reviews added; one review including similar data to a previously included systematic review,and one review including observational data reporting on harms.Categorisation of 'carotid endarterectomy in people with less than 30% symptomatic carotid artery stenosis' unchanged (Likely to be ineffective or harmful).
• Carotid endarterectomy in people with moderate (30–49%) symptomatic carotid artery stenosis Two systematic reviews added; one review including similar data to a previously included systematic review,and one review including observational data reporting on harms.Categorisation of 'carotid endarterectomy in people with moderate (30–49%) symptomatic carotid artery stenosis' unchanged (Unlikely to be beneficial).
• Carotid endarterectomy in people with moderately severe (50–69%) symptomatic carotid artery stenosis Two systematic reviews added; one review including similar data to a previously included systematic review,and one review including observational data reporting on harms.Categorisation of 'carotid endarterectomy in people with moderately severe (50–69%) symptomatic carotid artery stenosis' unchanged (Beneficial).
• Carotid endarterectomy in people with severe (more than 70%) symptomatic carotid artery stenosis Two systematic reviews added; one review including similar data to a previously included systematic review,and one review including observational data reporting on harms.Categorisation of 'carotid endarterectomy in people with severe (more than 70%) symptomatic carotid artery stenosis' unchanged (Beneficial).
• Carotid endarterectomy in people with symptomatic near occlusion of the carotid artery Two systematic reviews added; one review including similar data to a previously included systematic review,and one review including observational data reporting on harms.Categorisation of 'carotid endarterectomy in people with symptomatic near occlusion of the carotid artery' unchanged (Unlikely to be beneficial).
• Carotid percutaneous transluminal angioplasty One systematic review added comparing carotid percutaneous transluminal angioplasty versus carotid endarterectomy which pools data; categorisation of 'carotid percutaneous transluminal angioplasty' unchanged (Unknown effectiveness).
• Carotid percutaneous transluminal angioplasty plus stenting One systematic review added which included data from both symptomatic and asymptomatic people;'carotid percutaneous transluminal angioplasty plus stenting' categorised as Unknown effectiveness.
• Anticoagulant treatment in people with atrial fibrillation and previous stroke or TIA Two RCTs added; one comparing clopidogrel plus aspirin versus adjusted-dose oral anticoagulation therapy,and one comparing warfarin (INR 2.0–3.0) versus the oral thrombin inhibitor ximelagatran.Categorisarion of 'oral anticoagulants' unchanged (Beneficial).
• Antiplatelet treatment in people with atrial fibrillation and previous stroke or TIA One RCT added comparing clopidogrel plus aspirin to adjusted-dose oral anticoagulation treatment.Categorisation of 'aspirin' unchanged (Unknown effectiveness).

New evidence; conclusion confirmed for:

• Adjuvant chemotherapy One systematic review and one subsequent RCT added comparing adjuvant chemotherapy versus surgery alone. The review found that adjuvant chemotherapy reduced mortality compared with surgery, but the subsequent RCT found no significant difference in mean survival rates between adjuvant chemotherapy and surgery alone. Categorisation unchanged (Likely to be beneficial).