• Interferon plus ribavirin in treatment-naïve people One systematic review added found that a significantly smaller proportion of people achieved SVR with interferon plus ribavirin compared with peginterferon plus ribavirin. Although evidence suggests that interferon plus ribavirin is less effective than peginterferon plus ribavirin, there is evidence that combination interferon treatment is more effective than interferon monotherapy. Categorisation unchanged (Beneficial).
• Peginterferon plus ribavirin in treatment-naïve people One RCT added found that peginterferon plus ribavirin (dose based on patient's weight) increased the proportion of people achieving sustained virological response (SVR) compared with peginterferon plus placebo. One systematic review added found that, in treatment-naïve people, peginterferon plus ribavirin significantly increased the proportion of people achieving SVR compared with standard interferon plus ribavirin. Six RCTs added assessed the effects of different durations of treatment with peginterferon plus ribavirin. The reported RCTs vary in their comparisons of treatment duration and in genotype of people included. The RCTs found different results for end-of-treatment and sustained virological response for various treatment durations compared with each other. One RCT added comparing peginterferon plus fixed dose ribavirin versus peginterferon plus weight-based dose of ribavirin found that weight-based ribavirin improved rate of SVR (all genotypes) compared with fixed dosage of ribavirin.Categorisation unchanged (Beneficial).
• Interferon alfa plus ribavirin in non-responders to interferon One systematic review added found no significant difference between standard interferon plus ribavirin and peginterferon plus ribavirin in the proportion of interferon non-responsive people achieving sustained virological response. Evidence included data reported in only abstract form. Categorisation unchanged (Beneficial).
• Peginterferon plus ribavirin in non-responders to interferon One systematic review added found no significant difference between standard interferon plus ribavirin and peginterferon plus ribavirin in the proportion of interferon non-responsive people achieving sustained virological response. Evidence included data reported in only abstract form, and we found no evidence on the effects of peginterferon plus ribavirin compared with no active treatment. Categorisation unchanged (Unknown effectiveness).
• Peginterferon plus ribavirin in people who have relapsed One systematic review added identified no new evidence meeting Clinical Evidence reporting criteria. Categorisation unchanged (Likely to be beneficial by consensus).
• Interferon alfa plus ribavirin in people co-infected with hepatitis C virus and HIV One systematic review and one subsequent RCT added found that a smaller proportion of people achieved sustained virological response (SVR) with interferon plus ribavirin compared with peginterferon plus ribavirin. Subgroup analyses based on HCV genotype found that interferon plus ribavirin was less effective at achieving SVR than peginterferon plus ribavirin in people with genotype 1 or 4 and 1 alone, but there was no significant difference between treatments in people with genotypes 2 or 3. Categorisation unchanged (Likely to be beneficial).
• Peginterferon plus ribavirin in people co-infected with hepatitis C virus and HIV One systematic review and one subsequent RCT added found that a larger proportion of people achieved sustained virological response (SVR) with peginterferon plus ribavirin compared with interferon plus ribavirin. Subgroup analyses based on HCV genotype found that peginterferon plus ribavirin was more effective at achieving SVR than interferon plus ribavirin in people with genotype 1 or 4 and 1 alone, but there was no significant difference between treatments in people with genotypes 2 or 3. The review also found peginterferon plus ribavirin to be more effective at achieving SVR compared with peginterferon alone.A separate analysis of one RCT identified by the review assessed the effect of treatments on liver histological response. The RCT found that the proportion of people with a histological response was significantly larger with peginterferon plus ribavirin compared with interferon plus ribavirin and compared with peginterferon alone. Categorisation unchanged (Likely to be beneficial).
• Peginterferon in people co-infected with hepatitis C virus and HIV One systematic review added found peginterferon alone to be less effective at achieving SVR compared with peginterferon plus ribavirin. We found no evidence on the effects of peginterferon alone compared with no active treatment. Categorisation unchanged (unknown effectiveness).

• Fluoxetine to treat PTSD Two RCTs added found no significant difference between fluoxetine and placebo in PTSD symptoms at the end of treatment (8–12 weeks). One of the RCTs also found no significant difference between fluoxetine and placebo in the proportion of people no longer meeting diagnostic criteria for PTSD at the end of treatment. One RCT compared fluoxetine versus eye movement desensitisation and reprocessing (EMDR). It found no significant difference between treatments in PTSD symptoms at the end of treatment. However, EMDR was found to be more effective at sustaining improvement in symptoms at 6 months compared with fluoxetine. Evidence added at update suggests effects of fluoxetine in treating PTSD are unclear. Categorisation changed (from Likely to be beneficial to Unknown effectiveness).

New evidence; conclusion confirmed for:

• Antiepileptic drugs to prevent PTSD One small RCT added found that a similar proportion of people with a severe injury was diagnosed with PTSD at 4 months' follow-up after initial treatment with gabapentin for 14 days compared with those given placebo. The RCT was underpowered to detect a clinically meaningful difference. Categorisation unchanged (Unknown effectiveness).
• Antihypertensive drugs to prevent PTSD One small RCT added found that the proportion of people with severe injury diagnosed with PTSD at 4 months' follow-up after initial treatment with propranolol for 14 days was the same as that for those given placebo. The RCT was underpowered to detect a clinically meaningful difference. Categorisation unchanged (Unknown effectiveness).
• Antiepileptic drugs to treat PTSD Two RCTs added assessing the effects of topiramate and tiagabine found no significant difference between the antiepileptic drugs assessed and placebo in PTSD symptoms at the end of treatment. Categorisation unchanged (Unknown effectiveness).
• CBT to treat PTSD Three RCTs added, which found that CBT improved PTSD symptoms compared with no treatment. One RCT added comparing CBT (prolonged exposure) versus present-centred therapy found greater improvements in PTSD symptoms immediately after treatment and at 3 months' follow-up with CBT. However, there was no significant difference between groups in PTSD symptoms at 6 months. The proportion of women no longer meeting diagnostic criteria for PTSD was larger immediately after treatment with CBT than with present-centred therapy. Categorisation unchanged (Beneficial).
• Eye movement desensitisation and reprocessing to treat PTSD One small RCT added found that eye movement desensitisation and reprocessing (EMDR) improved symptoms of PTSD and reduced the proportion of people fulfilling criteria for PTSD compared with no treatment. One RCT comparing EMDR versus fluoxetine found no significant difference between treatments in PTSD symptoms at the end of treatment. However, EMDR was found to be more effective at sustaining improvement in symptoms at 6 months compared with fluoxetine. Categorisation unchanged (Beneficial).
• Sertraline to treat PTSD One RCT added found no significant difference between sertraline and placebo in PTSD symptoms at 12 weeks.Categorisation unchanged (Unknown effectiveness).

• Zoledronate New option, for which we identified two RCTs. The first RCT found that zoledronate reduced new vertebral fractures, new non-vertebral fractures (all types), and new hip fractures compared with placebo during 3 years' follow-up. The second RCT found that zoledronate reduced new clinical vertebral fractures and new non-vertebral fractures compared with placebo during follow-up (median 1.9 years).It found no significant difference between zoledronate and placebo in new hip fractures during follow-up (median 1.9 years).Categorised as Beneficial.

New evidence; conclusion confirmed for:

• Alendronate One systematic review added supersedes three previously reported reviews: the new review found similar studies and reached similar conclusions. The review pooled data from studies examining alendronate 10 mg daily versus 5 to 10 mg daily in the previous reviews to match current recommendations of a pooled weekly dose of 70 mg. The review found that alendronate reduced vertebral and non-vertebral fractures compared with control (placebo or calcium with or without vitamin D). Harms data added for osteonecrosis of the jaw, atrial fibrillation, and stress fractures associated with bisphosphonates. Categorisation unchanged (Beneficial).
• Risedronate One systematic review added. The review replaces two previously reported systematic reviews as it includes all the studies found by the earlier reviews and reaches similar conclusions. The new systematic review examined risedronate 5 mg daily to better match current recommendations of risedronate 35 mg weekly versus the previous reviews, which examined risedronate 2.5 to 5 mg daily. It found that risedronate reduced vertebral and non-vertebral fractures compared with control (placebo or calcium with or without vitamin D). Categorisation unchanged (Beneficial).
• Etidronate One systematic review added.This new review supersedes two earlier reviews as it identified all of the same studies, reached similar conclusions, and provided more information than the previous reviews. The review found that etidronate reduced the proportion of women with vertebral fractures compared with control (placebo or calcium with or without vitamin D). However, there was no significant difference between groups in rate of non-vertebral fractures. Categorisation unchanged (Likely to be beneficial).
• Raloxifene One systematic review added to the harms section. It found increased risk of either deep venous thromboembolism or pulmonary embolism with raloxifene compared with placebo after median follow-up of 24 months.Categorisation unchanged (Trade-off between benefits and harms).
• Hormone replacement therapy One RCT added to the harms section. It found increased rate of cardiovascular events and venous thromboembolism in women taking combined hormone replacement therapy compared with placebo. It found no significant difference in rates of cerebrovascular disease, or in rates of breast cancer or other cancers between groups after 11.9 months.Categorisation unchanged (Likely to be ineffective or harmful).
• Calcium alone One systematic review added. It found no significant difference between calcium supplementation (1000–1600 mg/day) and placebo in non-vertebral fractures at 2–5 years. It found that calcium supplementation (800–1200 mg/day) significantly increased hip fractures compared with placebo at 2–5 years.Categorisation unchanged (Unlikely to be beneficial).
• Vitamin D alone One systematic review updated.The review now includes one RCT previously reported as a subsequent RCT in this Clinical Evidence review. It found no significant difference between vitamin D alone and placebo or no treatment in any new fracture between 1 and 5.2 years' follow-up. Categorisation unchanged (Unlikely to be beneficial).
• Vitamin D analogues (alfacalcidol or calcitriol) One systematic review updated. It found that alfacalcidol had a borderline-significant effect in reducing the risk of non-vertebral fracture, and reduced hip fractures in older people with impaired mobility. Categorisation unchanged (Likely to be beneficial).
• Calcium plus vitamin D One systematic review updated. The review found that calcium plus vitamin D reduced hip fractures and non-vertebral fractures (all types) compared with placebo or no treatment. Categorisation unchanged (Likely to be beneficial).
• Multifactorial non-pharmacological interventions One systematic review added, which includes two RCTs previously described separately in this Clinical Evidence review. The review did not analyse RCTs and cohort studies separately. It found no significant difference between multifactorial non-pharmacological interventions and control (no programme or single interventions) in the risk of fractures, either in hospital or in a care-home setting. Categorisation unchanged (Unknown effectiveness).

• Education about acute asthma One systematic review (search date 2006) added comparing education versus usual care in adults who had attended an emergency department for asthma exacerbation. It found that education reduced hospital admissions compared with usual care, but it found no significant difference in subsequent presentations to emergency departments, primary care physician urgent visits, primary care physician call outs, quality of life, physical limitations caused by asthma, or lung function, between education and control. Evidence added at update does not support evidence previously reported on effects of education about asthma. Considering evidence added at update, categorisation changed from "Beneficial" to "Unknown effectiveness".
• Magnesium sulphate One systematic review (search date 2007) added found no significant difference in hospital admissions or respiratory function between intravenous magnesium sulphate and control; however, heterogeneity among RCTs was reported. Considered with evidence previously reported, categorisation changed from "Likely to be beneficial" to "Unknown effectiveness".
• Adding isotonic nebulised magnesium to inhaled beta₂ agonists One systematic review added (search date 2007) found no significant difference in hospital admissions or respiratory function between intravenous magnesium sulphate and control; however, heterogeneity among RCTs was reported. In six of the seven RCTs in the review, people in both the nebulised magnesium sulphate and control groups also received beta₂ antagonists. Evidence reassessed. Categorisation changed from "Likely to be beneficial" to "Unknown effectiveness".

New evidence; conclusion confirmed for:

• Adding long-acting inhaled beta₂ agonists to inhaled corticosteroids in people with mild-to-moderate persistent asthma that is poorly controlled by inhaled corticosteroids One updated systematic review (search date 2006) found that long-acting inhaled beta₂ agonists plus inhaled corticosteroids decreased exacerbations and the need for rescue medications, and increased the number of symptom-free days, rescue-free days, quality-of-life scores, morning and evening peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV₁) compared with leukotriene antagonists plus inhaled corticosteroids. However, it found no significant difference between the two groups in hospital admissions. One RCT added comparing salmeterol plus fluticasone versus salmeterol alone versus fluticasone alone found that, compared with fluticasone alone, salmeterol plus fluticasone improved change in morning PEF at 12 months, and decreased the need for rescue medication at 12 months; however, it found no significant difference between the groups in PEF diurnal variation, FEV₁, and forced vital capacity. Categorisation unchanged (Beneficial).
• Low-dose inhaled corticosteroids in people with persistent asthma Two systematic reviews added (search dates 1999 and 2007) and two systematic reviews updated (search date 2005 and search date 2003). The first systematic review found no significant difference between budesonide and placebo in lung function, but found that budesonide reduced the use of inhaled beta₂ agonists compared with placebo. The other three systematic reviews found that low-dose inhaled corticosteroids improved lung function and reduced the need for short-acting bronchodilators compared with placebo. Categorisation unchanged (Beneficial).
• Short-acting inhaled beta₂ agonists as needed in adults with mild or moderate asthma One updated systematic review (search date 2002) found no significant difference between regular and as-needed beta₂ agonists in morning PEFR, major exacerbations, daytime and night-time symptom scores, or quality-of-life scores in adults or children with a diagnosis of asthma for at least 6 months. However, the review found varying results for FEV₁ and rescue bronchodilator use between parallel group and crossover RCTs. In the parallel group RCTs, as-needed beta₂ agonists improved FEV₁ compared with regular treatment, but the difference was not significant in the crossover RCTs. Additionally, in the parallel group RCTs, regular beta₂ agonists reduced rescue bronchodilator use over a 24-hour period compared with as-needed use, but the difference was not significant in the crossover RCTs. Categorisation unchanged (Beneficial).
• Inhaled corticosteroids One systematic review updated (search date 2005) and one systematic review added (search date 2006). The updated systematic review found that inhaled corticosteroids given in the emergency department in people with acute asthma reduced hospital admission rates and improved lung function compared with placebo. The new systematic review found that multiple doses of inhaled corticosteroids reduced hospital admissions and increased discharge rates compared with placebo, and it found a dose response relationship between inhaled corticosteroids and lung function at 60 and 120 minutes. The review found no significant difference in hospital admissions between multiple dose inhaled corticosteroids and systemic corticosteroids; however, it found that multiple dose inhaled corticosteroids increased discharge rates and lung function compared with systemic corticosteroids. Categorisation unchanged (Beneficial).
• Adding anticholinergics (ipratropium bromide) to beta₂ agonists One RCT added found no significant difference between albuterol plus ipratropium bromide and albuterol alone in improvement in PEFR and in hospital admissions. However, the RCT had weak methods and may have been underpowered to detect clinically important differences between groups. Categorisation unchanged (Beneficial).
• Systemic corticosteroids One updated systematic review (search date 2006) found that systemic corticosteroids reduced relapse rate, hospital readmissions, and use of beta₂ agonists compared with placebo; however, it found no significant difference in pulmonary function test between systemic corticosteroids and placebo. Categorisation unchanged (Beneficial).
• Continuous nebulised short-acting beta₂ agonists One updated systematic review (search date 2008) found that continuous nebulised short-acting beta₂ agonists reduced hospital admissions and improved pulmonary function compared with intermittent nebulised short-acting beta₂ agonists. Categorisation unchanged (Likely to be beneficial).
• Helium–oxygen mixture (heliox) One systematic review updated (search date 2005) comparing helium–oxygen mixture (heliox) and oxygen or air (control). It found no significant difference in hospital admission between heliox and control, and no significant difference in pulmonary function between heliox and control; however, there was significant heterogeneity for the outcome of pulmonary function. An analysis of people with moderate to severe asthma found that heliox improved pulmonary function compared with control. Categorisation unchanged (Unlikely to be beneficial).

• Magnesium sulphate: Two systematic reviews added to the comments section. The first review reported that the percentage of women with a successful delay of delivery by 48 hours was 53% with control/placebo and 89% with magnesium sulphate. The percentage of women with successful delay of labour until 37 weeks was 36% with control/placebo and 42% with magnesium sulphate. Neonatal mortality occurred in 2% with placebo and 1% with magnesium sulphate. Overall rates of adverse effects were 1% with placebo and 3% with magnesium sulphate. However, no direct comparisons were made in this review. The second review reported that magnesium sulphate given before preterm delivery for neuroprotection has demonstrated a reduction in cerebral palsy and substantial gross motor dysfunction. Categorisation changed from Likely to be ineffective or harmful to Unlikely to be beneficial.

New evidence; conclusion confirmed for:

• Progesterone: One systematic review and two subsequent RCTs added comparing progesterone versus placebo in women with a history of spontaneous preterm birth, for women with a short cervix identified on ultrasound, and in women with a multiple pregnancy. For women with a history of spontaneous preterm birth, the review and the first subsequent RCT found that progesterone decreased the risk of preterm birth before 37 or 34 weeks, birth weight of under 2500 g, and necrotising enterocolitis compared with placebo. They found no significant difference between groups in neonatal or perinatal mortality. The review found no significant difference between groups in respiratory distress syndrome or intraventricular haemorrhage. The review found that women with a short cervix were less likely to have a preterm birth before 34 weeks with progesterone compared with placebo. The review also found that progesterone decreased the rate of neonatal sepsis compared with placebo, but it found no significant difference between groups in any other outcome. For women with a multiple pregnancy, the review and the second subsequent RCT found no significant difference between progesterone and placebo for neonatal or perinatal mortality, birth before 37 weeks, respiratory distress syndrome, mean gestational age at birth, or birth weight under 2500 g. However, the review found that progesterone decreased the need for tocolysis compared with placebo.Categorisation unchanged (Likely to be beneficial).
• Antibiotic treatment for premature rupture of membranes: One systematic review updated and one long-term RCT follow-up added. The long-term follow-up RCT found no difference in the number of children born to mothers exposed to erythromycin, amoxicillin, or both, for the composite outcome of death and any functional impairment or respiratory disorders compared with placebo at 7 years. Categorisation unchanged (Likely to be beneficial).
• Calcium-channel blockers : Three subsequent RCTs added comparing nifedipine versus magnesium sulphate, or ritodrine.The first two subsequent RCTs found that nifedipine decreased the rate of delay of delivery for 48 hours and the rate of NICU admission compared with magnesium sulphate. These RCTs also found no difference between groups in delivery before 32 or 37 weeks' gestation, morbidity, birth weight under 2500 g, respiratory distress syndrome, mean gestational age at birth, or number of episodes of recurrent preterm birth. The third RCT found no difference between nifedipine and ritodrine in rates of delivery delayed for 48 hours, delivery after 34 weeks' gestation, respiratory distress syndrome, infection, or longer term childhood outcomes measured at 2 years compared with ritodrine. One systematic review added to the comments section. The review found that percentage of women with a successful delay of delivery by 48 hours and a successful delay of labour until 37 weeks' gestation was higher for calcium-channel blockers than for placebo. Overall rates of adverse effects were similar in both groups. However no direct comparisons were made between interventions. Categorisation unchanged (Likely to be beneficial).
• Beta mimetics: One systematic review added to the comments section.The review found that a higher proportion of women given beta mimetics had a successful delay of delivery by 48 hours than those given placebo. However, the review made no direct comparisons between groups.Categorisation unchanged (unlikely to be beneficial)
• Antibiotic treatment for preterm labour with intact membranes: One systematic review added comparing antibiotics versus placebo/control.The review found no differences between groups for average latency or neonatal infection. One 7-year follow-up study of the largest RCT in the review added to harms. It found an increased proportion of children with any functional impairment and proportion of children with total death or cerebral palsy whose mothers had received erythromycin compared with no erythromycin. Categorisation unchanged (Unlikely to be beneficial).

• Music therapy: New option for which we found no studies. Categorised as Unknown effectiveness.
• Cognitive behavioural therapy: New option for which we found no studies. Categorised as Unknown effectiveness.
• Facilitated communication: New option for which we found no studies. Categorised as Unknown effectiveness.
• Melatonin: New option for which we found no studies. Categorised as Unknown effectiveness.
• Olanzapine: New option for which we found no studies. Categorised as Unknown effectiveness.

New evidence; conclusion confirmed for:

• Early intensive behavioural interventions: One systematic review added comparing early intensive behavioural interventions versus other therapy. The review found that early intensive behavioural interventions improved group mean scores for IQ, comprehension, and adaptive behaviour. However individual outcomes were varied. Categorisation unchanged (Likely to be beneficial).
• Picture exchange communication system: Two RCTs added comparing the picture exchange communication system (PECS) versus prelinguistic milieu teaching, delayed PECS training, or control. The first RCT found that PECS improved the frequency of non-imitative speech and words compared with prelinguistic milieu teaching. The second RCT found that PECS improved the rate of initiations and the PECS use compared with no treatment, but it found no differences between groups on scores of speech frequency, communication, or language. Categorisation unchanged (Likely to be beneficial).
• Risperidone: One systematic review added comparing risperidone versus placebo. The review found that risperidone improved global function, irritability, social withdrawal, hyperactivity, stereotypy, and inappropriate speech compared with placebo. However, the review also reported that risperidone increased the risk of weight gain. One additional RCT added to the harms section reported that risperidone increased serum prolactin levels at 8 weeks, 6 months, and 22 months compared with placebo. Categorisation unchanged (Trade-off between benefits and harms).
• SSRIs: One systematic review added including no RCTs or cohort studies that met our criteria. Categorisation unchanged (Trade-off between benefits and harms).

• CBT Two systematic reviews and one RCT added. These supersede three older previously reported systematic reviews, as they provided more information, included many of the same studies, and reached similar conclusions. Categorisation changed from Unknown effectiveness to Likely to be beneficial.
• Hypnotherapy Two systematic reviews added. These supersede a previously reported early narrative systematic review as they include some of the same studies, provide more information, and reach similar conclusions. One of the new systematic reviews carried out a meta-analysis and found that hypnotherapy reduced global symptoms or abdominal pain compared with placebo.Categorisation changed (from Unknown effectiveness to Likely to be beneficial).

New evidence; conclusion confirmed for:

• Antidepressants Two systematic reviews and one RCT added. The two reviews supersede three older systematic reviews previously reported in this Clinical Evidence review, which included some of the same studies and reached similar conclusions. Categorisation unchanged (Likely to be beneficial).
• Antispasmodics One systematic review and one RCT added. The review supersedes two older systematic reviews previously reported in this Clinical Evidence review, which included many of the same studies and reached similar conclusions. Categorisation unchanged (Likely to be beneficial).
• Soluble fibre supplementation One systematic review added. This supersedes an older systematic review previously reported in this Clinical Evidence review, which included many of the same studies and reached similar conclusions. Categorisation unchanged (Likely to be beneficial).
• Insoluble fibre supplementation One systematic review added. This supersedes an older systematic review previously reported in this Clinical Evidence review, which included many of the same studies and reached similar conclusions. Categorisation unchanged (Unknown effectiveness).
• 5HT₄ receptor agonists One systematic review added. This systematic review supersedes two older previously reported reviews, as it reports many of the same RCTs and reaches the same conclusion. Categorisation unchanged (Trade-off between benefits and harms).
• 5HT₃ receptor antagonists: One systematic review added comparing alosetron versus placebo. It pooled results from five RCTs previously reported in this Clinical Evidence review and three subsequent RCTs. It found that alosetron significantly improved global symptoms or abdominal pain compared with placebo. Categorisation unchanged (Trade-off between benefits and harms).
• 5HT₃ receptor antagonists other than alosetron (ramosetron) One RCT added.It found that ramosetron increased response to treatment and patient-reported relief of abdominal pain or discomfort and improvement in abnormal bowel habits compared with placebo after 12 weeks' treatment. Categorisation unchanged (Unknown effectiveness).

• Levothyroxine (L-thyroxine) plus liothyronine for clinical (overt) hypothyroidism One systematic review added comparing L-thyroxine alone versus a combination of L-thyroxine plus liothyronine (L-tri-iodothyronine) in people with primary hypothyroidism. The review added no further data than already included and also found no difference between groups in psychiatric symptoms. Categorisation unchanged (Unlikely to be beneficial).
• Levothyroxine (L-thyroxine) for subclinical hypothyroidism One systematic review added comparing thyroid hormone replacement versus placebo or no treatment. The review found that hormone replacement improved general symptoms and cognitive function compared with placebo or no treatment, but found no difference between groups for quality of life or health-related quality of life.Categorisation unchanged (Unknown effectiveness).

• Imidazoles (intravaginal): One systematic review added comparing intravaginal imidazoles versus oral fluconazole or itraconazole. The review found no significant difference between intravaginal treatment and oral treatment in clinical cure at short- and long-term follow-up, or mycological cure at short-term follow-up. However, intravaginal imidazoles were less effective than oral treatment with fluconazole or itraconazole for achieving long-term mycological cure. Categorisation of intravaginal imidazoles unchanged (Beneficial).
• Fluconazole (oral): One systematic review added comparing oral fluconazole versus oral itraconazole. The review found no significant difference between groups for clinical or mycological cure with follow-up of the included studies, ranging from 10 days to 8 weeks. Categorisation unchanged (Beneficial).
• Yoghurt containing Lactobacillus acidophilus: One RCT added comparing lactobacillus versus placebo after one dose of fluconazole (150 mg) at 1 month. The RCT found that lactobacillus decreased vaginal discharge and the presence of yeast detected by culture compared with placebo. Categorisation unchanged (Unknown effectiveness).

• Monovalent measles immunisation or combined MMR immunisation versus placebo or no immunisation: Three self-controlled case series added to harms, which found increased rates of febrile convulsions, idiopathic thrombocytopenic purpura (ITP), fever, rash, and diarrhoea after MMR immunisation. One self-controlled case series added to harms, which found no cases of aseptic meningitis after MMR immunisation containing RIT 4385 mumps immunisation strain. Categorised as Beneficial.
• Monovalent rubella immunisation or combined MMR immunisation versus placebo or no immunisation : One population-based study added to benefits, which found that endemic cases of rubella were rare in the USA between 2001 and 2004. One case study added to benefits, reporting an outbreak of rubella in a non-immunised community. Categorised as Beneficial.

• Progesterone: One systematic review (2 RCTs; 281 women) found no overall improvement in premenstrual symptoms in women taking luteal-phase progesterone for 2 to 4 months compared with placebo. Categorisation changed from Trade-off between benefits and harms to Unknown effectiveness.

New evidence; conclusion confirmed for:

• SSRIs: One systematic review and one subsequent RCT added to benefits and harms, both of which found that SSRIs improved premenstrual symptoms, but were associated with a number of adverse effects, including nausea, insomnia, headache, asthenia, and decreased libido. Categorisation unchanged (Trade-off between benefits and harms).
• Oral contraceptives: One systematic review found that ethinyloestradiol plus drospirenone may reduce the symptoms of premenstrual syndrome. Categorisation unchanged (Likely to be beneficial).
• Progestogens: One new RCT added, which found that a 5-day regimen of chlormadinone reduced symptoms of premenstrual syndrome. Categorisation unchanged (Trade-off between benefits and harms).
• Pyridoxine: One new RCT added, which found that pyridoxine improved psychiatric symptoms of premenstrual syndrome. Categorisation unchanged (Beneficial).

• Anterior colporrhaphy with mesh reinforcement versus traditional anterior colporrhaphy One systematic review updated, reporting no additional RCTs, so no new data added. Three subsequent RCTs added. One RCT found that anterior colporrhaphy with porcine skin collagen implant at 1-year follow-up was more effective than anterior colporrhaphy without implant in preventing anatomical anterior recurrence. Two RCTs found that anterior colporrhaphy with polypropylene mesh was more effective than anterior colporrhaphy without mesh in preventing cystocoele recurrence at 1 year. Categorisation unchanged (Beneficial).

• Cilostazol One systematic review added, including RCTs already reported in this Clinical Evidence review. Evidence re-evaluated. Categorisation changed from Trade-off between benefits and harms to Likely to be beneficial.

New evidence; conclusion confirmed for:

• Antiplatelet agents One systematic review added, reporting that antiplatelet agents (aspirin or aspirin plus dipyridamole) reduced arterial occlusion of both venous and artificial peripheral bypass grafts versus placebo at 12 months. It found no significant difference in GI adverse effects, or major bleeding between groups. One RCT added, reporting lower MI rates with clopidogrel plus aspirin versus placebo plus aspirin after 26 months, but no significant difference in the overall combined rate of cardiovascular death, MI, or stroke between groups. It found no significant difference in fatal, severe, or moderate bleeding or primary intracranial haemorrhage between groups. Categorisation unchanged (Beneficial).
• Exercise Two systematic reviews and one subsequent RCT added. One review found that exercise, for between 12 weeks and 2 years, increased maximum walking distance and pain-free walking distance versus usual care/placebo. It found no significant difference between groups in the ankle brachial index. The other review also found increased pain-free walking distance and maximum walking distance with exercise versus usual care. The RCT found improved quality of life, assessed by short form-36 (SF-36) physical functioning score and by the distance and stair-climbing scores of the Walking Impairment Questionnaire, with treadmill exercise or resistance training versus control. However, it found no significant difference between either exercise and control in the speed score of the Walking Impairment Questionnaire. Categorisation unchanged (Beneficial).
• Bypass surgery One systematic review updated, which now includes one RCT previously described separately in this Clinical Evidence review. Another RCT added, which found no significant difference in primary patency between percutaneous transluminal angioplasty (PTA) plus stent placement versus femoro-above-knee popliteal bypass grafting at 6, 12, or 24 months. Categorisation unchanged (Likely to be beneficial).
• Statins One further report of one RCT, already included in this Clinical Evidence review, added. Categorisation unchanged (Likely to be beneficial).
• Percutaneous transluminal angioplasty (PTA) One RCT added, comparing PTA versus optimal medical treatment. It found an improvement in both pain-free walking distance and maximum walking distance and visual analogue pain score with optimal medical treatment alone versus PTA at 24 months. However, it found no significant difference in quality of life between groups at 24 months.Categorisation unchanged (Likely to be beneficial).
• Prostaglandins One RCT added. It found no significant difference in major amputation rates or death with lipo-ecraprost (intravenously for 8 weeks) versus placebo at 6 months.Categorisation unchanged (Trade-off between benefits and harms).

• Endovascular coiling versus surgical clipping One follow-up report of an included RCT added, which found that endovascular coiling increased retreatment rates for the same aneurysm compared with surgical clipping at 4.5 to 12 years, but it did not assess the significance of the difference between groups. Categorisation unchanged (Beneficial).
• Nimodipine (oral) One systematic review updated with new data from RCTs. The review confirmed its previous conclusion that oral nimodipine reduced clinical signs of secondary ischaemic, radiological signs of cerebral infarction, and the combined outcome of dependence or death compared with placebo or no treatment. It found no significant difference in mortality between groups. Categorisation unchanged (Beneficial).
• Nimodipine (intravenous) One systematic review updated with new data from RCTs. The review confirmed its previous conclusion that intravenous followed by oral nimodipine reduced clinical signs of secondary ischaemic and radiological signs of cerebral infarction compared with placebo or no treatment. However, it again found no significant difference in mortality or the combined outcome of dependence or death between groups. Categorisation unchanged (Unknown effectiveness).

• Intranasal antihistamines (azelastine) Four RCTs added comparing intranasal azelastine versus placebo. Three of the RCTs found that azelastine reduced nasal symptom severity compared with placebo, but one found no significant difference between groups.Two further RCTs added, which found no significant difference between azelastine and oral cetirizine in nasal symptom severity; one of the RCTs found that azelastine improved quality of life scores compared with cetirizine.One small RCT added comparing azelastine with oral loratadine, which found no significant difference between groups in nasal symptom severity.Categorisation changed (from Unknown effectiveness to Beneficial)

New evidence; conclusion confirmed for:

• Intranasal corticosteroids Eight RCTs added comparing intranasal corticosteroids versus placebo (2 RCTs of ciclesonide, 4 RCTs of fluticasone, 1 RCT of budesonide, and 1 RCT of mometasone). Seven of the RCTs found that intranasal corticosteroids reduced nasal symptom severity compared with placebo. One of the RCTs also found that fluticasone significantly improved quality of life scores. One RCT found no significant difference in nasal symptom severity between mometasone and placebo. Several further RCTs added comparing intranasal corticosteroids with active controls. One RCT compared budesonide versus fluticasone and found no significant difference in nasal symptom severity between groups.One RCT found fluticasone reduced nasal symptoms compared with intranasal levocabastine.One RCT found similar improvements in nasal symptom severity with fluticasone and azelastine at 2 weeks, but did not assess the significance of the difference between groups.Two RCTs found that fluticasone significantly reduced nasal symptom severity compared with montelukast. Categorisation unchanged (Beneficial)
• Antihistamines (oral) One systematic review and three RCTs added comparing oral antihistamines versus placebo (1 RCT of cetirizine, 1 RCT of ebastine, 1 systematic review, and 1 RCT of desloratadine ), which all found that oral antihistamines reduced nasal symptoms compared with placebo. One further RCT added, which found that intranasal fluticasone plus oral levocetirizine reduced nasal symptom severity compared with intranasal fluticasone alone.Categorisation unchanged (Beneficial)
• Antihistamines (intranasal; levocabastine and olopatadine) Two RCTs (reported in 3 papers) added comparing intranasal olopatadine versus placebo, both of which found olopatadine reduced nasal symptom severity compared with placebo. Categorisation unchanged (Likely to be beneficial)
• Leukotriene receptor antagonists (oral) One systematic review and one additional RCT added. The systematic review found that montelukast reduced nasal symptom severity compared with placebo. The RCT, in people with both asthma and hay fever, found that montelukast reduced daytime nasal symptom severity, but found no significant difference in night-time nasal symptom severity.Two further RCTs added comparing leukotriene receptor antagonists versus active controls. One RCT found no significant difference between zafirlukast and oral cetirizine. One RCT found that pseudoephedrine reduced night-time quality-of-life scores compared with montelukast, but found no significant difference between groups in daytime quality of life.Categorisation unchanged (Likely to be beneficial)
• Leukotriene receptor antagonists (oral) plus antihistamines (oral) One systematic review and one subsequent RCT added. The systematic review found that leukotriene receptor antagonists plus antihistamines significantly reduced nasal symptom severity compared with oral antihistamines alone. The subsequent RCT found that zafirlukast plus cetirizine reduced nasal symptom severity compared with cetirizine alone. Two further small crossover RCTs added comparing montelukast plus cetirizine versus intranasal corticosteroids, but both provided only limited data on symptom severity. Categorisation unchanged (Unlikely to be beneficial)
• Decongestants (oral) plus antihistamines (oral) One RCT added comparing pseudoephedrine plus desloratadine versus either treatment alone. It found that the combination treatment reduced nasal symptom severity compared with either treatment alone. Categorisation unchanged (Beneficial)

• Antidepressant drugs for tinnitus One RCT added comparing sertraline (25 mg/day for 1 week followed by 50 mg/day for 15 weeks) versus placebo. It found that sertraline improved tinnitus severity and loudness, clinician-rated anxiety, participant-rated anxiety, and participant-rated depression compared with placebo. However, it found no significant difference between sertraline and placebo in tinnitus annoyance and clinician-rated depression. Considering all evidence reported, potential benefits of antidepressant drugs in the treatment of tinnitus are unclear. Categorisation changed from Trade-off between benefits and harms to Unknown effectiveness.

New evidence; conclusion confirmed for:

• Ginkgo biloba One systematic review updated (search date 2006), identifying the same RCTs as previously reported in this Clinical Evidence review. Categorisation unchanged (Unknown effectiveness).

• Early initiation of highly active antiretroviral treatment Two cohort studies added. One prospective study found mortality was increased the longer HAART initiation was delayed after starting antituberculosis treatment, and found decreased mortality in people with bacteriologically confirmed tuberculosis, who started HAART within the first 120 days of antituberculosis treatment versus people who started HAART later than this. Another study (retrospective from 1996 to 2000; prospective from 2000 to 2004) found better survival in people who started HAART within 2 months of starting antituberculous treatment versus people who started HAART more than 3 months after antituberculous treatment.Categorisation unchanged (unknown effectiveness).

• Alginate dressing One systematic review added (search date 2008), which found no RCTs that met Clinical Evidence inclusion criteria. Categorisation unchanged (Unknown effectiveness).
• Chlorhexidine-impregnated paraffin gauze dressing One systematic review added (search date 2008), which did not pool data, and found no additional RCTs to those previously reported in this Clinical Evidence review. Categorisation unchanged (Unknown effectiveness).
• Foam dressing One systematic review added (search date 2008),which found no RCTs. Categorisation unchanged (Unknown effectiveness).
• Hydrocolloid dressing One systematic review added (search date 2008), which did not pool data and found no additional RCTs to those previously reported in this Clinical Evidence review. Categorisation unchanged (Unknown effectiveness).
• Hydrogel dressing One systematic review added (search date 2008), which found no RCTs that met the inclusion criteria for this Clinical Evidence review. One additional RCT added, which found that a liposome hydrogel including polyvinylpyrrolidone iodine reduced time to wound closure compared with silver sulfadiazine cream; however, the RCT found similar results for clinician assessments of inflammation and healing, and similar results for participant assessments of pain and itching, with both the polyvinylpyrrolidone iodine hydrogel and silver sulfadiazine cream. Categorisation unchanged (Unknown effectiveness).
• Polyurethane film One systematic review added (search date 2008), which did not pool data and found no additional RCTs to those previously reported in this Clinical Evidence review. Categorisation unchanged (Unknown effectiveness).
• Silicone-coated nylon dressing One systematic review added (search date 2008), which did not pool data and found no additional RCTs to those previously reported in this Clinical Evidence review. Categorisation unchanged (Unknown effectiveness).
• Silver sulfadiazine cream One systematic review added (2008), which did not pool data and found no additional RCTs to those previously reported in this Clinical Evidence review. Categorisation unchanged (Unknown effectiveness).

• Tonsillectomy versus no surgery in adults One systematic review added identifying one RCT that met Clinical Evidence inclusion criteria. The RCT found that tonsillectomy reduced the frequency and duration of sore throat at 5 to 6 months, but had short follow-up. Categorisation unchanged (Trade-off between benefits and harms).

New evidence; conclusion confirmed for:

• Tonsillectomy versus no surgery in children One systematic review updated (4 RCTs; 564 children), which found that tonsillectomy reduced the number of episodes of sore throat, and duration of sore throat compared with standard care at 1 to 3 years. Categorisation unchanged (Trade-off between benefits and harms).

• Statins versus placebo or no treatment One systematic review and two subsequent RCTs added. The review found that statins reduced all-cause mortality and cardiovascular mortality compared with placebo or no treatment. The first subsequent RCT found that simvastatin decreased all-cause mortality, major coronary events, and the composite outcome of death from coronary disease and non-fatal MI compared with placebo. The second subsequent RCT found no significant difference between pravastatin and placebo or no treatment in rates of progression to end-stage renal disease (ESRD), composite outcome of ESRD or 50% decrease in glomerular filtration rate (GFR), or the composite outcome of ESRD or 25% decrease in GFR. Categorisation changed from Unknown effectiveness to Likely to be beneficial.

New evidence; conclusion confirmed for:

• ACE inhibitors One RCT added comparing trandolapril versus placebo with a median follow-up of 4.8 years. It found that trandolapril reduced all-cause mortality compared with placebo in people with a glomerular filtration rate (GFR) of less than 60 mL/minute/1.73 m². Categorisation unchanged (Likely to be beneficial).
• ACE inhibitors plus angiotensin II receptor antagonist versus either drug alone One RCT added comparing ACE inhibitors plus angiotensin II receptor antagonists versus ACE inhibitors alone. The RCT found that ACE inhibitors plus candesartan significantly increased the level of serum creatinine at 3 years and significantly decreased urinary protein excretion at 1, 2, and 3 years compared with ACE inhibitors alone. Categorisation unchanged (Likely to be beneficial).
• Angiotensin II receptor antagonists Three RCTs added, one comparing angiotensin II receptor antagonists versus placebo,and two comparing angiotensin II receptor antagonists versus ACE inhibitors. The first RCT found that valsartan did not decrease progression to end-stage renal disease (ESRD) or rates of doubling in serum creatinine level, but it did decrease proteinuria and slowed the mean rate of decline of glomerular filtration rate (GFR) compared with placebo at 2 years. The second RCT found that angiotensin II receptor antagonists did not decrease the rate of progression to ESRD compared with ACE inhibitors. The third RCT found no significant difference between angiotensin II receptor antagonists and ACE inhibitors in the composite outcome of doubling of the serum creatinine, ESRD, or mortality. Categorisation unchanged (Unknown effectiveness).
• Targeted lowering of albuminuria/proteinuria One RCT added comparing up-titrated benazepril or losartan versus non-titrated benazepril or losartan. The RCT found that up-titrated doses of both benazepril and losartan reduced the risk of the composite outcome of doubling of serum creatinine, end-stage renal disease (ESRD), or death compared with the non-titrated doses. Categorisation unchanged (Unknown effectiveness).
• Lowering blood pressure below usual targets Two additional outcomes added for the African American Study of Renal Disease (AASK) trial in two papers. The first paper reported that the RCT found no significant difference between low and usual target blood pressure in cardiovascular mortality, cardiovascular composite outcome of cardiovascular death or admission to hospital for CVD, or all cardiovascular events, including multiple events in the same person. The second paper reported that the RCT found no significant difference in mean change in composite physical health or the composite mental health outcomes of the Short Form 36 between groups over the 4 years of the study. Categorisation unchanged (likely to be beneficial)

• Single- or multiple-session brief intervention in hazardous or harmful drinkers in primary care One systematic review and one subsequent RCT added comparing single- or multiple-session brief interventions with either control or extended interventions. Categorisation unchanged (Beneficial).
• Brief intervention (single- or multiple-session) in emergency departments One systematic review and one subsequent RCT added comparing single-session brief intervention (BI) with control. The review found no significant difference between single-session BI and control in quantity of or frequency of alcohol consumption, but found that single-session BI significantly decreased the number of alcohol-related injuries compared with control at 12 months. The subsequent RCT found that single-session BI reduced alcohol consumption at 12 months compared with baseline. Categorisation unchanged (Likely to be beneficial).

• H pylori eradication treatments (quadruple regimens compared with triple regimens as second-line treatment) New option for which we found three RCTs. The RCTs found that quadruple regimens as second-line therapies were more effective than triple regimens at eradicating H pylori. Most triple regimens given did not contain a nitroimidazole. Categorised as Likely to be beneficial.
• H pylori eradication treatments (sequential regimens compared with triple regimens as first-line treatment) New option for which we found one systematic review. The review found sequential therapy was more effective at increasing H pylori eradication rates compared with proton pump inhibitor triple regimens. Categorised as Likely to be beneficial.

New evidence; conclusions changed for:

• H pylori eradication treatments (quadruple regimens compared with triple regimens as first-line treatment) One systematic review results updated and published as a letter to the editor.The review found no significant difference in eradication rates between quadruple regimens and triple regimens. Categorisation changed from Likely to be beneficial to Unlikely to be beneficial with the rationale that quadruple regimens are no more effective than triple regimens. Adding a fourth drug to initial eradication treatment confers no additional benefit.
• H pylori eradication treatments (duration of H pylori eradication as first-line treatment) Three RCTs added, which found no significant difference in H pylori eradication rates between 1-week and 2-week triple regimens, although in all three RCTs eradication rates were higher with 2-week regimens. Categorisation unchanged: both Likely to be beneficial, but the 2-week triple regimen is more effective than the 1-week triple regimen.

New evidence; conclusion confirmed for:

• H pylori eradication (in uninvestigated dyspepsia) Three RCTs added. The first RCT found that eradication treatment was more effective at improving dyspepsia symptoms than placebo in long-term proton pump inhibitor users.Two RCTs found similar dyspepsia scores with test and treat, prompt endoscopy, and empirical eradication treatment. Categorisation unchanged (beneficial).
• H pylori eradication treatments (different triple regimens compared with each other) Four systematic reviews and 12 RCTs added. One systematic review and three RCTs (2 RCTs reported in 1 publication) found that nitroimidazole-based triple regimens and amoxicillin-based triple regimens were equally effective at eradicating H pylori. Two RCTs found no significant difference in H pylori eradication rates between higher and lower dose clarithromycin within nitroimidazole-based triple regimens. Three systematic reviews and three subsequent RCTs found no significant difference in H pylori eradication rates between different proton pump inhibitor-based triple regimens. Four RCTs found lower eradication rates in people infected with strains of H pylori resistant to antibiotics included in the eradication regimen compared with people infected with sensitive strains. It is unclear whether any one triple regimen is more effective than another. Categorisation unchanged (Unknown effectiveness).

• Photodynamic treatment One systematic review added. It found that photodynamic treatment was more effective at wart clearance than placebo or cryotherapy, and that neutral red photodynamic treatment and proflavine photodynamic treatment have similar effects. Categorisation unchanged (Likely to be beneficial).
• Intralesional bleomycin Data from one systematic review updated, and one RCT added. The RCT found that intralesional bleomycin increased wart clearance compared with placebo. Categorisation unchanged (unknown effectiveness).
• Duct tape occlusion One systematic review and two RCTs (3 publications) added. The systematic review found no significant difference in wart clearance between duct tape occlusion and cryotherapy. The two RCTs found no significant difference in wart clearance between duct tape occlusion and placebo. One of the RCTs also found no significant difference in wart recurrence between duct tape occlusion and placebo. Categorisation unchanged (Unknown effectiveness).
• Pulsed dye laser One RCT added, which found no significant difference in wart clearance between pulsed dye laser and placebo. Categorisation unchanged (Unknown effectiveness)

• Rotavirus vaccines New option for which we found one systematic reviewand eight subsequent RCTs; one RCT was reported in two papers. The systematic review found that live-attenuated bovine rotavirus vaccine and human-attenuated rotavirus vaccine were safe, and significantly reduced the number of episodes and severe episodes of gastroenteritis caused by rotavirus, and admissions to hospital with gastroenteritis caused by rotavirus, compared with placebo. The eight subsequent RCTs found similar results. Categorised as Beneficial.
• Ondansetron New option for which we found one systematic review. The review did not pool data because of clinical heterogeneity among the RCTs and a paucity of data. Three RCTs identified by the review found that ondansetron reduced episodes of vomiting compared with placebo. The RCTs found that ondansetron was associated with an increased risk of diarrhoea compared with placebo, but the RCTs were small in size and, taken together, do not provide sufficient evidence to draw a definitive conclusion regarding adverse effects of ondansetron. Categorised as Likely to be beneficial.

New evidence; conclusions changed for:

• Loperamide One systematic review added, which found that loperamide significantly reduced the mean duration of diarrhoea compared with placebo. However, the incidence of adverse effects was significantly higher in children treated with loperamide compared with placebo; all serious adverse effects occurred in children under 3 years of age. Categorisation changed from Likely to be beneficial to Trade-off between benefits and harms.