• Counselling people to increase physical activity versus no counselling: effects on level of physical activity One systematic review and three RCTs added to the existing reporting of three systematic reviews and 12 RCTs. The added systematic review did not pool data in our group of interest, and the three RCTs were therefore reported separately. Two of the added RCTs found that counselling increased physical activity, whereas the third found no significant difference among groups in physical activity. Categorisation unchanged (Likely to be beneficial).

• Intra-articular injections (of hyaluronan or corticosteroid) New option for which we found no systematic review or RCTs in people with osteoarthritis of the hip. Categorised as Unknown effectiveness.
• Hip resurfacing New option for which we found no systematic review or RCTs in people with osteoarthritis of the hip. Categorised as Unknown effectiveness.
• Arthroscopic debridement New option for which we found no systematic review or RCTs in people with osteoarthritis of the hip. Categorised as Unknown effectiveness.

New evidence; conclusion confirmed for:

• Acupuncture One systematic review added, which found no new evidence on the effects of acupuncture in people with osteoarthritis of the hip. One RCT added, which found that at 3 months, compared with no acupuncture, needle acupuncture improved WOMAC scores for pain, stiffness and function, and SF-36 physical component. However, the RCT found no significant difference between groups in the mental component of the SF-36 questionnaire. Categorisation unchanged (Unknown effectiveness).

• ABVD plus radiotherapy versus radiotherapy alone (stage I or II non-bulky Hodgkin's lymphoma) New option added for which we found one RCT. The RCT found that two cycles of ABVD plus radiotherapy improved freedom from treatment failure (composite outcome), and reduced risk of relapse at 7 years. However, the RCT found no significant difference between treatments in overall survival at 7 years. Categorised as Likely to be beneficial by consensus (ABVD plus radiotherapy is considered the international gold standard for early-stage Hodgkin's lymphoma).

New evidence; conclusion confirmed for:

• ABVD (stage II [bulky], III, or IV Hodgkin's lymphoma) One RCT added found that ABVD may be more effective than Stanford V at reducing disease recurrence (various outcomes) at 5 years, and as effective as MOPPEBVCAD. The RCT found similar rates for overall survival at 5 years for ABVD, Stanford V, and MOPPEBVCAD. Categorisation unchanged (Beneficial).
• ABVPP plus radiotherapy versus ABVPP alone One long-term follow-up studyadded found lower rates of survival at 10 years with combination treatment compared with ABVPP alone, which supported findings from 5-year follow-up. Categorisation unchanged (Unlikely to be beneficial).
• MOPP/ABV plus radiotherapy versus MOPP/ABV alone One long-term follow-up study added found similar rates of survival at 10 years with combination treatment compared with MOPP/ABV alone, which supported findings from 5-year follow-up. Categorisation unchanged (Unlikely to be beneficial).

• Advice to promote room sharing (without bed sharing): We found no direct evidence on the effects of room sharing (without bed sharing) on the prevention of SIDS. Categorised as Unknown effectiveness.

New evidence; conclusion confirmed for:

• Advice to avoid prone sleeping : One retrospective cohort study added assessing the change in incidence of SIDS in the 20 years since advice to avoid prone position sleeping campaign. The study found that factors contributing to SIDS have changed during this time period. Two observational studies added to the harms section assessing the effects of supine sleeping position on deformational plagiocephaly. The first observational study documented a temporal relationship between advice to avoid prone sleeping and an increase in the incidence of occipital plagiocephaly without synostosis. However, the incidence of other forms of plagiocephaly with synostosis did not change. The second observational study found that supine sleeping position was not a significant determinant of deformational plagiocephaly, but that sleeping with the head turned to the same side is a significant factor.Categorisation unchanged (Beneficial).
• Advice to avoid tobacco-smoke exposure: One retrospective cohort study added assessing the effect of smoking on SIDS. The study found that smoke-exposed infants were significantly more likely to die of SIDS. Categorisation unchanged (Likely to be beneficial).

• Nasal CPAP (severe OSAHS) Three systematic reviews and three subsequent RCTs added comparing nasal CPAP versus placebo, no treatment, or conservative treatment. They found different results on blood pressure with CPAP versus placebo, no treatment, or conservative treatment. They found reduced daytime sleepiness and sleep disturbance, but no significant difference in performance in some neuropsychological test components with CPAP versus placebo, no treatment, or conservative treatment. Categorisation unchanged (Beneficial).
• Measures aimed at improving compliance with nasal CPAP (severe OSAHS) One RCT added comparing ongoing CPAP treatment versus switching to bi-level positive airway pressure treatment. It found improved compliance with switching to bi-level positive airway treatment compared with ongoing CPAP treatment, but no significant difference in quality of life between groups after 90 days. One RCT added comparing intensive early support versus standard support found no significant difference in mean CPAP nightly use or daytime sleepiness between groups at 1 or 6 months' follow-up. Categorisation unchanged (Unknown effectiveness).
• Nasal CPAP (non-severe OSAHS) One systematic review added comparing CPAP versus control treatments, including oral placebo tablets, sham CPAP, or conservative management. The review found that CPAP improved subjective daytime sleepiness, and objective daytime wakefulness, but did not significantly improve objective daytime sleepiness compared with control after 3–24 weeks. Categorisation unchanged (Likely to be beneficial).
• Oral appliances (non-severe OSAHS) One RCT added comparing active versus inactive oral appliance, which found reduced daytime sleepiness, number of sleep arousals, and sleep-disordered breathing, and improvements in some components of quality of life and depression indices. One RCT added comparing CPAP plus conservative measures versus oral appliance plus conservative measures. It reported reduced sleep-disordered breathing and daytime sleepiness, and improvements in one domain of quality-of-life survey. It found no significant difference in other domains of quality-of-life survey or blood pressure reduction. One RCT added comparing oral appliance versus CPAP, which found no significant difference between groups in sleep-disordered breathing or in subjective measures of daytime sleepiness after 2–3 months. One already included systematic review updated, no new data added. Categorisation unchanged (Likely to be beneficial).
• Measures aimed at improving compliance with nasal CPAP (non-severe OSAHS) One RCT added comparing CPAP versus automatically titrated CPAP found no significant difference between groups in sleep-disordered breathing, daytime sleepiness, or compliance after 8 weeks. One RCT added comparing group cognitive behavioural therapy (CBT) versus usual treatment found higher compliance with CPAP in people who received group CBT after 4 weeks of treatment. Categorisation unchanged (Unknown effectiveness).

• Acupressure for treating hyperemesis gravidarum: One RCT added, which found that acupressure was more effective at reducing nausea and vomiting episodes compared with placebo and control (conventional intravenous fluid). Categorised as Likely to be beneficial.
• Metoclopramide for treating hyperemesis gravidarum: One RCT found that metoclopramide was less effective at reducing vomiting episodes and readmission to the intensive care unit compared with corticosteroids. Other drugs and interventions may be more useful. Categorised as Unlikely to be beneficial.

New evidence; conclusion confirmed for:

• Acupressure for treating nausea and vomiting in early pregnancy: One systematic review and two RCTs added. The systematic review found that acupressure applied as a wristband reduced the proportion of women reporting nausea and vomiting compared with control. One RCT found no significant difference between acupressure and placebo in the number of women who reported nausea and vomiting. The RCT comparing acupressure and pyridoxine found no significant difference between the two treatments in Rhodes index scores. Categorisation unchanged (Likely to be beneficial).
• Antihistamines (H₁ antagonists) for treating nausea and vomiting in early pregnancy: One RCT added. The RCT found that the antihistamine dimenhydrinate improved vomiting for the first 2 days compared with ginger, but there was no significant difference at days 3–7. It also found no significant difference in nausea scores between the two groups. Categorisation unchanged (Likely to be beneficial).
• Ginger for treating nausea and vomiting in early pregnancy: Two RCTs added. One RCT found that ginger was more effective at reducing nausea and vomiting scores compared with pyridoxine. One RCT comparing ginger and antihistamines found that that dimenhydrinate improved vomiting for the first 2 days compared with ginger, but there was no significant difference at days 3–7. It also found no significant difference in nausea scores between the two groups. Categorisation unchanged (Likely to be beneficial).
• Pyridoxine (vitamin B₆ ) for treating nausea and vomiting in early pregnancy: Two RCTs added. The RCT comparing acupressure and pyridoxine found no significant difference between the two treatments in Rhodes index scores. The other RCT found that pyridoxine was less effective compared with ginger at reducing nausea and vomiting scores. Categorisation unchanged (Likely to be beneficial).
• Acupuncture for treating nausea and vomiting in early pregnancy: One systematic review added. The review identified the same RCTs already reported and came to similar conclusions. Categorisation unchanged (Unknown effectiveness).

• Patient-delivered partner therapy New option for which we found one review. The review found that supplementing patient referral with patient-delivered partner therapy reduced risk of recurrent or persistent infection in index patients compared with patient referral alone. Categorised as Likely-to-be-beneficial.
• Health education plus counselling New option for which we found two reviews. One published RCT identified by the reviews found that more male index patients who received individual counselling plus health education reported that their partners were treated, compared with those male patients receiving simple patient referral. However, the RCT found similar rates between groups in the number of partners reported by female index patients as having received treatment. One unpublished RCT reported by one review found that, compared with patient referral alone, counselling plus education significantly increased the number of partners elicited and the number of partners treated per index patient. Categorised as Unknown effectiveness.
• Home-sampling kit for partners New option for which we found one review. One quasi-RCT identified by the review found that home sampling increased the rate of partners tested per index patient compared with sampling by healthcare provider. However, the RCT found no significant difference between groups in the rate of partners testing positive for infection per index patient. Categorised as Unknown effectiveness.

New evidence; conclusions changed for:

• Contract referral in people with HIV infection One RCT reported comparing composite intervention of patient plus provider referral (a type of contract referral) versus patient referral alone. It found that contract referral increased the number of partners notified compared with patient referral alone. Categorisation changed from Unknown effectiveness to Likely-to-be-beneficial.

New evidence; conclusion confirmed for:

• Counselling alone One systematic review added found no new evidence on the effects of counselling alone in improving partner referral rates. Categorisation unchanged (Unknown effectiveness).
• Health education One systematic review added. Two published RCTs identified by the review assessed the effects of supplementing patient referral with health education, one using a verbal presentation and one using an educational video. One RCT found no significant difference between groups in the rate of partners treated per index patient and one RCT found no significant difference between groups in the rate of partners tested. Categorisation unchanged (Unknown effectiveness).
• Information pamphlets One review added identified two RCTs, which reported conflicting results for the effects of supplementing patient referral with partner-directed information compared with simple patient referral. Both RCTs measured effects on the proportion of partners reported as taking treatment. Categorisation unchanged (Unknown effectiveness).

• Natalizumab in people with relapsing and remitting multiple sclerosis: Two RCTs identified. One RCT found the proportion of relapse-free people at 2 years was higher with natalizumab compared with placebo. The other RCT also found that the proportion of relapse-free people at 2 years and the cumulative probability of sustained disability progression at 2 years was higher with natalizumab plus interferon beta-1a compared with interferon beta-1a alone. However, the long-term benefits and risks of natalizumab are still unknown. Categorised as Trade-off between benefits and harms.
• Natalizumab in people with acute relapse of multiple sclerosis: One RCT identified, which found no significant difference in Expanded Disability Status Scale (EDSS) between natalizumab and placebo at 14 weeks. Categorised as Unknown effectiveness.

New evidence; conclusions changed for:

• Physiotherapy One RCT added, which found that combining physiotherapy with botulinum toxin further improved spasticity scores compared with botulinum toxin alone. Categorisation unchanged (Unknown effectiveness).
• Inpatient rehabilitation One systemic review added, which identified one RCT already reported in this review. Categorisation unchanged (Unknown effectiveness).

New evidence; conclusion confirmed for:

• Glatiramer acetate (parenteral) in people with relapsing and remitting multiple sclerosis One RCT added, which found no significant difference in the delay to sustained progression of accumulated disability between glatiramer acetate and placebo at 3 years. Categorisation unchanged (Likely to be beneficial).
• Interferon beta in people having a first demyelinating event or with relapsing and remitting multiple sclerosis One systematic review and two RCTs added. The review and one subsequent RCT found that interferon beta was more effective at reducing the risk of a second clinical event and, therefore, of conversion to a definite diagnosis of multiple sclerosis at 1 and 3 years. The other RCT found the proportion of relapse-free people at 2 years and the cumulative probability of sustained disability progression at 2 years was higher with natalizumab plus interferon beta-1a compared with interferon beta-1a alone. Categorisation unchanged (Likely to be beneficial).
• Azathioprine One systematic review added, which found that azathioprine was more effective at reducing the number of people relapsing at 3 years and at improving disability scores at 2 years compared with placebo. Categorisation unchanged (Trade-off between benefits and harms).
• Exercise One RCT added, which found no significant changes in Expanded Disability Status Scale (EDSS) with exercise compared with no exercise. Categorisation unchanged (Unknown effectiveness).
• Drug treatments (oral) One RCT added, which found no significant difference in spasticity scores between cannabis oromucosal spray and placebo. Categorisation unchanged (Unknown effectiveness).
• Outpatient rehabilitation One systematic review added, which found that outpatient rehabilitation improved physical functioning, bodily pain, general health, vitality, social functioning, and mental health domains of the SF-36 (36-item Short Form Health Survey Questionnaire) quality-of-life measures. Categorisation unchanged (Unknown effectiveness).

• Defibrillation (biphasic compared with monophasic shock) New option for which we found five RCTs and one subsequent analysis comparing biphasic versus monophasic defibrillation. The RCTs found no significant differences between groups in survival, but the studies may be underpowered to show clinically important differences. Overall, the evidence found that biphasic shock increased the number of successful defibrillations compared with monophasic shock for out-of-hospital cardiac arrests. Categorised as Likely to be beneficial.

• Alpha-blockers in people with symptomatic ureteric stones New option for which we found two systematic reviews and three subsequent RCTs, which all found that alpha-blockers increased the proportion of people with expelled stones compared with placebo at times ranging from 1 to 7 weeks. However, both systematic reviews reported heterogeneity among RCTs. Categorised as Likely to be beneficial.

New evidence; conclusion confirmed for:

• Extracorporeal shockwave lithotripsy (ESWL) in people with renal stones One systematic review added, which found no significant difference in treatment success rates between ESWL using 120 shocks per minute and 60 shocks per minute at 10 days to 3 months.Categorisation unchanged (Likely to be beneficial).
• Ureteroscopy in people with mid- and distal ureteric stones One systematic review added, which found that ureteroscopy increased the proportion of people who were stone free compared with extracorporeal shockwave lithotripsy at 1–3 months.Categorisation unchanged (Trade-off between benefits and harms).

• Preoperative chemotherapy in resectable non-small cell lung cancer Two systematic reviews and one subsequent RCT added comparing preoperative chemotherapy versus surgery alone. The first review found that preoperative chemotherapy significantly increased 5-year survival compared with surgery alone. The second review found that preoperative chemotherapy significantly increased survival at 1 and 3 years, but not at 5 years compared with surgery alone. The subsequent RCT found no significant difference between groups for 5-year survival. Categorisation changed (from Unknown effectiveness to Trade-off between benefits and harms).
• First-line platinum-based chemotherapy versus non-platinum regimens in unresectable non-small cell lung cancer One systematic review and two RCTs added comparing first-line platinum-based chemotherapy versus non-platinum regimens. The review found that cisplatin-based two-drug regimens improved survival at 1 year compared with non-platinum-based two-drug regimens, but there was no significant difference in 1-year survival with carboplatin-based two-drug regimens compared with non-platinum-based two-drug regimens. The first subsequent RCT found no significant difference between groups in median survival. The second subsequent RCT found that combined response rates were significantly higher for platinum-based three-drug therapy compared with platinum-free two-drug therapy, but found no significant difference in 1-year survival rates. Categorisation changed (from Likely to be beneficial to Trade-off between benefits and harms).

New evidence; conclusion confirmed for:

• Postoperative adjuvant chemotherapy in resected non-small cell lung cancer Three RCTs added comparing postoperative chemotherapy versus surgery alone. The first RCT found that adjuvant chemotherapy (cisplatin plus etoposide) significantly increased 10-year survival in people with fully resected disease, but not overall survival in people with minimally resected disease at 10 years compared with surgery alone. The second RCT found that adjuvant chemotherapy significantly increased the 8-year overall survival in people with stage 1 disease, but not 8-year overall survival in people with stage 2 and 3A disease compared with surgery alone. The third RCT found no significant difference in median survival time between the groups, but that adjuvant chemotherapy significantly increased the 2-year survival in people with brain metastases compared with surgery alone.Categorisation unchanged (Likely to be beneficial).
• First-line palliative chemotherapy with multiple agents versus with single-drug regimens in unresectable non-small cell lung cancer One systematic review updated comparing single- versus two-drug chemotherapy. The review found that adding a second agent significantly increased objective tumour response, 1-year survival, and median survival. However, the review also reported that two-drug regimens significantly increase toxicity compared with single-agent regimens. Categorisation unchanged (Trade-off between benefits and harms).
• Thoracic irradiation plus chemotherapy versus thoracic irradiation alone in unresectable lung cancer One systematic review added comparing chemoradiation versus radiotherapy alone. All six reviews included in the new evidence found that chemoradiation improved survival compared with radiotherapy alone at a minimum follow-up of 2 years.Categorisation unchanged (Beneficial).
• Second-line molecular-targeted therapy with gefitinib and erlotinib in unresectable lung cancer One systematic review added comparing gefitinib or erlotinib versus placebo, and dose comparisons of gefitinib or erlotinib. All RCTs identified were already included in the Clinical Evidence review, so no new data added. Categorisation unchanged (Unknown effectiveness).
• Second-line palliative chemotherapy versus supportive care in unresectable lung cancer One systematic review added comparing second-line docetaxel versus supportive care. The review found that second-line treatment with docetaxel increased 1-year and overall survival time, reduced pain, and improved quality-of-life scores compared with best supportive care, although no overall survival benefit was seen. Categorisation unchanged (Unknown effectiveness).
• Second-line single-agent chemotherapy regimens versus each other in unresectable lung cancer Two systematic reviews added comparing single-agent docetaxel versus another single-agent chemotherapy or best supportive care, and low-dose docetaxel once weekly versus high-dose docetaxel every 3 weeks. The first review made no direct comparisons between groups. The second review found no significant difference between low-dose docetaxel once weekly versus high-dose docetaxel every 3 weeks for overall survival. Categorisation unchanged (Unknown effectiveness).
• First-line molecular-targeted therapy with gefitinib and erlotinib in unresectable non-small cell lung cancer One systematic review added comparing gefitinib or erlotinib plus chemotherapy versus chemotherapy alone. The review found that none of the included RCTs showed significant improvements in median or overall survival from the addition of gefitinib or erlotinib to platinum-based first-line chemotherapy. Categorisation unchanged (Unlikely to be beneficial).
• Second-line multiple-agent chemotherapy compared with single-agent regimens One systematic review added, including one additional RCT comparing single-agent cisplatin versus combined cisplatin plus irinotecan. The RCT found no significant difference between groups for median and 1-year survival rates. Categorisation unchanged (Likely to be ineffective or harmful).
• Thoracic irradiation plus chemotherapy in limited-stage small cell lung cancer Two systematic reviews added comparing early versus late radiotherapy in people receiving chemotherapy. The reviews found no significant differences between groups for survival at 2, 3, and 5 years when all types of chemotherapy were included. However, one review reanalysed the data, excluding one RCT of non-platinum chemotherapy plus chest radiation, and found that survival at both 2 and 5 years was significantly increased with early radiotherapy. One of the reviews reported that early radiotherapy significantly increased the risk of oesophagitis and severe pneumonitis. Categorisation unchanged (Beneficial).
• Prophylactic cranial irradiation in people in complete remission from small cell lung cancer One RCT added comparing prophylactic cranial irradiation versus no irradiation.The RCT found that cranial irradiation significantly reduced the risk of symptomatic brain metastases and significantly increased survival compared with no irradiation. Categorisation unchanged (Likely to be beneficial).

• Salpingectomy: One retrospective cohort study added comparing expectant management versus salpingectomy. It found that salpingectomy did not increase the rate of subsequent pregnancy compared with expectant management. Categorisation unchanged (Beneficial).
• Salpingotomy: One systematic review updated, comparing salpingotomy by laparoscopy versus salpingotomy by laparotomy. It found that laparoscopy was less effective in achieving primary treatment success (elimination of tubal pregnancy) than laparotomy. However, it found no significant difference between groups in tubal patency, rate of subsequent pregnancy, and repeat ectopic pregnancy.Categorisation unchanged (Unknown effectiveness).
• Systemic methotrexate (single- or multiple-dose): One RCT added comparing single- versus multiple-dose methotrexate. It found no significant difference between groups in rates of success of medical management. One systematic review updated comparing single- or multiple-dose methotrexate versus laparoscopic salpingotomy. The review found that single-dose systemic methotrexate was significantly less effective than salpingotomy in increasing primary treatment-success rates (elimination of tubal pregnancy), but found no significant difference between multiple-dose systemic methotrexate and salpingotomy in primary treatment-success rates. Categorisation unchanged (Likely to be beneficial).
• Expectant management: One retrospective cohort added comparing expectant management versus salpingectomy. It found that expectant management increased the rate of subsequent pregnancy compared with salpingectomy but there remains insufficient evidence to draw conclusions about its use. Categorisation unchanged (Unknown effectiveness).

• Compliance therapy One systematic review added found no significant difference in the proportion of non-compliant people between those receiving compliance therapy and those receiving non-specific counselling therapy over 1 year. One RCT comparing adherence therapy versus health education found no significant difference between groups in either patient-rated or keyworker-rated measures of compliance at 12 months. Reassessment of evidence resulted in change of categorisation from Likely to be beneficial to Unknown effectiveness.

New evidence; conclusion confirmed for:

• Continuation of antipsychotic drugs (to reduce relapse rates) One systematic review added found that, in the longer term (longer than 1 year), depot fluphenazine decanoate reduced relapse rates compared with placebo. However, the review found no significant difference between groups in relapse rates in the shorter term (6–12 months). One systematic review added found that, compared with cessation of treatment, continued treatment with chlorpromazine for people already stable on medication for 8 weeks to 18 months reduced relapse rates for all time frames assessed (0 weeks to 24 months). One review added found continued treatment with second-generation antipsychotic drugs (olanzapine, ziprasidone, and zotepine) reduced relapse rates over 6–12 months compared with placebo. The also found that second-generation antipsychotic agents reduced relapse rates over 26–130 weeks' treatment compared with first-generation antipsychotic agents (predominantly haloperidol). Categorisation unchanged (Beneficial).
• Family interventions (to reduce relapse rates) One review added found that family-based psychosocial interventions reduced relapse rates compared with usual care at 7–12 months and at 19–24 months. However, there was no significant difference between groups in the shorter term (0–6 months) and longer term (25–36 months). One RCT added found no significant difference between a family mutual support group, a family psychoeducation group, and usual care in the mean number of hospital readmissions at 12 months and 18 months. Categorisation unchanged (Beneficial).
• Psychoeducational interventions (to reduce relapse rates) One RCT added found no significant difference in the mean number of hospital readmissions at 12 months and 18 months between a family psychoeducation group, a family mutual-support group, and usual care. Categorisation unchanged (Beneficial).
• CBT (to reduce relapse rates) One RCT added found that nurse-led CBT significantly reduced relapse rates compared with usual care at 12 months’ follow-up. Categorisation unchanged (Unknown effectiveness).
• Social-skills training One RCT found that a social-skills training programme reduced relapse rates at 24 months compared with group psychoeducation. One small RCT added compared social-skills training versus a supportive group-discussion programme. The RCT found similar rates of relapse in the treatment groups at 6 months. Categorisation unchanged (Unknown effectiveness).
• Clozapine versus other second-generation antipsychotic drugs (treatment-resistant disease) One RCT added comparing olanzapine versus clozapine in children and adolescents aged 7–16 years who had not responded to treatment with 2 antipsychotic medications found no significant difference between treatments at 8 weeks in change-in-symptom scores using various scales, although the RCT reported that there was a trend in improved symptoms that favoured clozapine. Categorisation unchanged (Unknown effectiveness).
• Second-generation antipsychotics (other than clozapine) versus first-generation antipsychotics (treatment-resistant disease) One RCT added found that ziprasidone improved Clinical Global Impression (CGI)-Severity scores at 6 weeks and Positive and Negative Symptom Severity (PANSS) Negative Subscale scores at 12 weeks compared with chlorpromazine, but found no difference between groups in proportion of people classed as responders. A second RCT added found no significant difference between aripiprazole and perphenazine at 6 weeks in various scales used to assess symptoms of schizophrenia.
• Psychoeducational interventions (to improve adherence) One small RCT added found no significant difference between an individual psychoeducational programme and usual care in the proportion of people showing "good compliance" to their pharmaceutical regimen at 6 months. Categorisation unchanged (Likely to be beneficial).
• Multiple-session family interventions (to improve adherence) One systematic review added found that family-based psychosocial interventions improved compliance with medication compared with usual care. However, the review included quasi-randomised RCTs and RCTs in people with schizoaffective disorder. Categorisation unchanged (Unknown effectiveness).

• Rifampicin plus isoniazid Two subsequent RCTs added to the existing reporting of one systematic review. One of the subsequent RCTs (470 people) was quasi-randomised, and the other RCT was small (105 people). Categorisation unchanged (Trade-off between benefits and harms).
• Regimens containing quinolones One already reported systematic review updated (search date 2007) to now include one further RCT, which was already reported in this review. Reporting in benefits and harms enhanced. Two other systematic reviews added (search dates 2006), which were narrative in character, and did not pool data. No further data added from these two reviews. Overall conclusions similar to before. Categorisation unchanged (Unknown effectiveness).
• Different drug regimens versus each other in multidrug-resistant tuberculosis Search date of one already included systematic review updated (to 2007).The systematic review still included the same pooled analysis of three included RCTs that was previously reported in this review. No new data added from the review. One subsequent RCT (134 people) added comparing adding high-dose isoniazid versus adding normal-dose isoniazid or placebo to second-line therapy. Categorisation unchanged (Unknown effectiveness).
• Direct observation treatment (DOT) versus self-administered treatment One already reported systematic review updated (search date 2007). New data added to benefits and harms sections, but overall conclusions of the updated review remain the same. Categorisation unchanged (Unlikely to be beneficial).
• Support mechanisms for directly observed treatment One systematic review (search date 2007) and two RCTs added including a variety of support mechanisms for DOT such as different sites, different support personnel (health workers or family members), or complex support interventions. Overall conclusions unchanged, with no clear differences in effectiveness between different support mechanisms. Categorisation unchanged (Unknown effectiveness).

• Serotonin reuptake inhibitors (duloxetine) One systematic review updated to now include one further RCT. One subsequent RCT added, which found reduced incontinence episode frequency but no significant improvement in quality of life with duloxetine compared with placebo. Categorisation changed (Beneficial to Likely to be beneficial).
• Non-tension-free vaginal tape/transobturator foramen tape suburethral slings One systematic review updated. One RCT added comparing suburethral slings other than tension-free vaginal tape (TVT) versus open retropubic colposuspension, found that non-TVT suburethral autologous sling improved overall urinary incontinence and specific urinary incontinence measures at 2 years' follow-up compared with open retropubic colposuspension. One systematic review added, comparing complications with suburethral slings versus TVT, found no significant difference in voiding lower urinary tract symptoms and clean intermittent catheterisation between TVT and pubo-vaginal slings. Categorisation changed (Beneficial).
• Transobturator foramen procedures Two systematic reviews and three RCTs added, comparing transobturator foramen procedures (TOT or TVT-O) versus tension-free vaginal tape (TVT), found no significant difference between procedures in failure of treatment or cure. One systematic review comparing complications of transobturator foramen procedures (TOT or TVT-O) versus TVT added. It found a lower incidence of bladder and vaginal perforations, haematoma, and storage and voiding lower urinary tract symptoms with transobturator foramen procedures (TOT or TVT-O) versus TVT. One RCT added, comparing TOT versus open retropubic colposuspension, found no significant difference between TOT and open retropubic colposuspension in cure of stress incontinence at 1-year' follow-up.Observational data added to harms section. Categorisation changed (from Unknown effectiveness to Likely to be beneficial).

New evidence; conclusion confirmed for:

• Pelvic floor muscle exercises Four systematic reviews updated. One systematic review reporting updated and one systematic review now includes one further RCT. Categorisation unchanged (Likely to be beneficial)
• Vaginal cones One systematic review updated to now include one further RCT. Categorisation unchanged (Likely to be beneficial).
• Laparoscopic colposuspension Four systematic reviews updated. Reporting updated for one systematic review. Categorisation unchanged (Beneficial).
• Open retropubic colposuspension Four systematic reviews updated. One RCT added comparing open retropubic colposuspension versus suburethral slings other than tension-free vaginal tape. It found that non-TVT suburethral autologous sling improved overall urinary incontinence and specific urinary incontinence measures at 2 years' follow-up compared with open retropubic colposuspension. One RCT added, comparing open retropubic colposuspension with transobturator foramen procedures. It found no significant difference in cure of stress incontinence at 1-year' follow-up. One systematic review comparing complications with open retropubic colposuspension versus tension-free vaginal tape added. It found that bladder/vaginal perforations were less common while re-operation rates were more common with open retropubic colposuspension. It found no significant differences between procedures in complications such as haematoma formation, urinary tract infection, storage, or voiding lower urinary tract symptoms. Categorisation unchanged (Beneficial).
• Tension-free vaginal tape (TVT) One systematic review updated. One RCT added, found improved Incontinence Quality of Life scores in elderly women with TVT versus no treatment after 6 months. Two systematic reviews and three RCTs added, found no significant difference in failure of treatment or cure with TVT versus transobturator procedures. One systematic review comparing complications with suburethral slings versus TVT added. It found no significant difference in voiding lower urinary tract symptoms and clean intermittent catheterisation between TVT and pubo-vaginal slings.Observational data added to harms section. Categorisation unchanged (Trade off between benefits and harms).

• Blood transfusion (prophylactic) sickle cell disease New option for which we found one systematic review identifying two RCTs. The review found that prophylactic blood transfusion significantly reduced the rate of stroke compared with standard care or no transfusion at 16–24 months. Categorised as a Trade-off between benefits and harms.

New evidence; conclusions changed for:

• Piracetam for sickle cell disease We found one systematic review comparing piracetam versus placebo. The review included three RCTs, but only one was reported fully. This RCT found that piracetam significantly reduced the incidence of sickle cell crisis compared with placebo. Categorisation changed from Likely to be beneficial to Unknown effectiveness.

New evidence; conclusion confirmed for:

• Zinc sulphate for preventing sickle cell disease We found one systematic review comparing zinc sulphate versus placebo. The review found that zinc sulphate significantly decreased the number of sickle cell crises compared with placebo. Categorisation unchanged (Likely to be beneficial).
• Hydration for sickle cell disease We found one systematic review that identified no RCTs.Categorisation unchanged (Unknown effectiveness).
• Diflunisal for sickle cell disease One systematic review added comparing diflunisal versus placebo. The review found no significant difference between groups for pain intensity. Categorisation unchanged (Unknown-effectiveness).
• Ketorolac for sickle cell disease One systematic review added comparing ketorolac versus placebo, ketorolac plus pethidine versus placebo plus pethidine, or ketorolac plus morphine sulphate versus placebo plus morphine sulphate. One RCT included in the review found that ketorolac significantly reduced pain compared with pethidine at 30 minutes, but had no significant difference between groups at 150 minutes. Two RCTs included in the review found that ketorolac plus pethidine did not significantly reduce pain compared with placebo plus pethidine. One RCT included in the review found no significant difference in the need for morphine between ketorolac compared with placebo. Categorisation unchanged (Unknown effectiveness).
• Corticosteroids for sickle cell disease One systematic review added comparing corticosteroids plus morphine versus placebo plus morphine. One RCT included in the review found a significant reduction in the duration of analgesia with dexamethasone compared with placebo. Another RCT included in the review found that methylprednisolone significantly reduced the duration of inpatient analgesia compared with placebo.Categorisation unchanged (Trade-off between benefits and harms).

• Cytokine inhibitors Follow-up data for 1 year was added to the RCT comparing infliximab versus placebo, and found no significant difference in pain, disability, cumulative sick leave, or proportion of people having discectomy. Categorisation unchanged (unknown effectiveness).
• Spinal manipulation One RCT added comparing manipulation alone versus acupuncture plus manipulation. Evaluated after 20 sessions, it found manipulation alone was less effective at improving pain. Categorisation unchanged (likely to be beneficial).
• Acupuncture One RCT added comparing acupuncture plus manipulation versus manipulation alone. Evaluated and found improvements in pain after 20 sessions. However, overall evidence on acupuncture remains too weak to draw conclusions. Categorisation unchanged (unknown effectiveness).
• Microdiscectomy One RCT added comparing early microdiscectomy versus conservative care (including later microdiscectomy if required). It found better outcomes in pain, function/disability, and patient-perceived recovery after 8 weeks with early microdiscectomy, but no significant difference in outcomes between groups at 1 and 2 years’ follow-up. One RCT added comparing microdiscectomy and open discectomy found no significant difference between groups in pain or disability at 3, 6, 12, or 24 months’ follow-up, or in time to return to work and normal activities. Categorisation unchanged (likely to be beneficial).
• Standard discectomy One RCT added comparing open discectomy and microdiscectomy. It found no significant difference between groups in pain or disability at 3, 6, 12, or 24 months’ follow-up, or in time to return to work and normal activities. Categorisation unchanged (likely to be beneficial).
• Percutaneous disc decompression One systematic review added, which identified no RCTs. Categorisation unchanged (unknown effectiveness).

• Vitamin E for leg cramps in pregnancy New option for which we identified no RCTs. Categorised as Unknown effectiveness.

New evidence; conclusions changed for:

• Quinine A drug safety alert has been issued by the FDA advising manufacturers to stop marketing unapproved drug products containing quinine, because of serious safety concerns. Among the adverse effects of quinine are cardiac arrhythmias, thrombocytopenia, severe hypersensitivity reactions, and death. Because of these serious adverse effects, and because the toxic dose for quinine is only slightly higher than the therapeutic dose, the FDA has suggested that people should be warned against treating their leg cramps with quinine products. The FDA alert relates to non-prescription drugs; in the UK, quinine is only available on prescription. In contrast to the FDA, the UK spontaneous adverse drug reaction reporting scheme (Yellow Card Scheme) has reported only 16 deaths associated with quinine between 1965 and 2008 and has not issued a drug safety alert in response to their findings. However, in line with the concerns regarding adverse effects, categorisation of quinine changed from Beneficial to Trade-off between benefits and harms.
• Quinine plus theophylline A drug safety alert has been issued by the FDA advising manufacturers to stop marketing unapproved drug products containing quinine because of serious safety concerns. Among the adverse effects of quinine are cardiac arrhythmias, thrombocytopenia, severe hypersensitivity reactions, and death. Because of these serious adverse effects, and because the toxic dose for quinine is only slightly higher than the therapeutic dose, the FDA has suggested that people should be warned against treating their leg cramps with quinine products. The FDA alert relates to non-prescription drugs; in the UK, quinine is only available on prescription. In contrast to the FDA, the UK spontaneous adverse drug reaction reporting scheme (Yellow Card Scheme) has reported only 16 deaths associated with quinine between 1965 and 2008 and has not issued a drug safety alert in response to their findings. However, in line with the concerns regarding adverse effects, categorisation of quinine plus theophylline changed from Likely to be beneficial to Trade-off between benefits and harms.

• Antifungal prophylaxis in adults having chemotherapy or radiotherapy One systematic review updated, which identified no additional RCTs. Categorisation unchanged (Beneficial).
• Antifungal treatment in adults having chemotherapy and radiotherapy One systematic review updated which identified no additional RCTs. Categorisation unchanged (Unknown effectiveness).
• Antifungal prophylaxis in people with HIV infection One systematic review added comparing antifungal prophylaxis versus placebo. It found that fluconazole, itraconazole, and nystatin all reduced rates of oral candidiasis compared with placebo at times between 1 week and 35 months. Categorisation unchanged (Beneficial)
• Topical antifungal treatment in people with HIV infection One systematic review added which found that oral ketoconazole and gentian violet both increased clinical cure compared with nystatin mouth wash at 14 days. It found no significant difference in cure between oral fluconazole and either clotrimazole lozenges or topical itraconazole solution at 7–14 days. It also found no significant difference in cure between miconzaole buccal tablets and oral ketoconazole at 14 days.
• Continuous antifungal prophylaxis versus intermittent antifungal treatment for reducing drug resistance One systematic review added, which identified no additional RCTs. Categorisation unchanged (Unlikely to be beneficial).

• Amantadine (oral) chemoprophylaxis One systematic review added comparing amantadine versus placebo in people aged up to 18 years, and in elderly people.None of the RCTs included in the review met our inclusion criteria. Amantadine has been associated with insomnia, hallucinations, and agitation. There is also consensus that amantadine should not be used for first-line chemoprophylaxis, because resistance to amantadine is high and it is only effective against influenza A. Categorisation changed (from Likely to be ineffective or harmful to Trade-off between benefits and harms).
• Rimantadine (oral) to treat influenza One systematic review added comparing rimantadine versus placebo in children and elderly people. It found no RCTs. There is consensus that rimantadine should not be used as first-line treatment, because cross-resistance to amantadine is high, and it is only effective against influenza A. Categorisation changed (from Likely to be ineffective or harmful to Trade-off between benefits and harms).

New evidence; conclusion confirmed for:

• Vaccines in children One systematic review added comparing live or inactive vaccine versus placebo or no vaccine.The review found that live or inactive vaccination significantly reduced the risk of laboratory-confirmed influenza or influenza-like illness in children up to 16 years. However, the review reported no significant difference in prevention of laboratory-confirmed influenza for children aged under 2 years between inactive vaccine and placebo. Categorisation unchanged (Likely to be beneficial).
• Zanamivir (orally inhaled) chemoprophylaxis One RCT added comparing prophylactic zanamivir versus placebo. The RCT found no significant difference between groups for confirmed cases of influenza. Categorisation unchanged (Likely to be beneficial).
• Rimanadine (oral) chemoprophylaxis One systematic review added comparing oral rimantadine prophylaxis versus placebo in children and in elderly people. It found no significant difference between groups for cases of influenza A in children or in elderly people. Categorisation unchanged (Likely to be ineffective or harmful).
• Amantadine (oral) to treat influenza One systematic review added comparing amantadine versus placebo for the treatment of influenza A in children and elderly people. The review found no significant protective effect for amantadine compared with placebo for fever on day 3 in children. The review found no RCTs in elderly people. Categorisation unchanged (Likely to be ineffective or harmful).

New option(s) added for:

• Corticosteroids New option. One systematic review found (search date 2003) which identified no RCTs comparing corticosteroids versus no corticosteroids.Three systematic reviews found (search date 2003, search date 2004) which identified the same small RCT (48 people) comparing corticosteroids versus corticosteroids plus whole-brain radiotherapy. 'Corticosteroids' categorised as Likely to be beneficial (categorisation made by consensus as insufficient RCT evidence found).
• Cytotoxic chemotherapy (systemic) New option. Three RCTs identified comparing either carboplatin plus whole-brain radiotherapy (WBRT) versus WBRT aloneor temozolomide plus WBRT versus WBRT alone. Two of the RCTs were terminated prematurely because of poor participant accrual. 'Cytotoxic chemotherapy (systemic)' categorised as Unknown effectiveness.
• Surgery New option. One systematic review (search date 2004) foundwhich identified no RCTs comparing surgery versus radiosurgery. One systematic review found (search date 2004) which identified one RCT (95 people) comparing surgery versus surgery plus whole-brain radiotherapy. 'Surgery' categorised as Unknown effectiveness.
• Surgery plus whole-brain radiotherapy (external beam) New option. One systematic review found (search date 2004) which identified one RCT (95 people) comparing surgery plus whole brain radiotherapy (WBRT) versus surgery alone. Two systematic reviews found (search date 2003; search date 2004) which identified the same three RCTs comparing surgery plus WBRT versus WBRT alone. 'Surgery plus WBRT (external beam)' categorised as Unknown effectiveness.
• Surgery plus radiosurgery New option. No RCTs found. 'Surgery plus radiosurgery' categorised as Unknown effectiveness.
• Surgery plus radiosurgery plus whole-brain radiotherapy (external beam) New option. No RCTs found. 'Surgery plus radiosurgery plus whole-brain radiotherapy (external beam)' categorised as Unknown effectiveness.
• Whole-brain radiotherapy (external beam ) New option. Three systematic reviews found (search date 2003, search date 2004) which identified the same small RCT (48 people) comparing corticosteroids plus whole-brain radiotherapy (WBRT) versus corticosteroids. Two systematic reviews found (search date 2003; search date 2004) which identified the same three RCTs comparing WBRT versus WBRT plus surgery. Three RCTs identified comparing either carboplatin plus WBRT versus WBRT aloneor temozolomide plus WBRT versus WBRT alone. Two of these RCTs were terminated prematurely because of poor participant accrual. Two systematic reviews (search date 2004) and one subsequently fully published RCTfound comparing WBRT plus radiation sensitisers versus WBRT alone. Three systematic reviews (search date 2004; search date not reported) found comparing WBRT versus WBRT plus radiosurgery. One further systematic review (search date 2004)which was a narrative review including both RCT and observational data added to the harms section and comments as background data. 'Whole-brain radiotherapy (external beam) (addition of some other interventions to WBRT may be no more effective than WBRT alone; WBRT alone may be effective in selected people)' categorised as Likely to be beneficial.
• Radiation sensitisers plus whole-brain radiotherapy (external beam) New option. Two systematic reviews found (search date 2004) and one subsequently fully published RCTcomparing whole-brain radiotherapy (WBRT) plus radiation sensitisers versus WBRT alone. 'Radiation sensitisers (no evidence that adding radiation sensitisers to WBRT is more effective than WBRT alone)' categorised as Unlikely to be beneficial.
• Whole-brain radiotherapy (external beam) plus radiosurgery New option. Three systematic reviews found (search date 2004; search date not reported) comparing whole-brain radiotherapy (WBRT) plus radiosurgery versus WBRT alone. One systematic review found (search date 2004) which identified one RCT in abstract form which has subsequently been published in full, comparing WBRT plus radiosurgery versus radiosurgery alone. 'Whole-brain radiotherapy (external beam) (WBRT) plus radiosurgery (some evidence of improved survival in people with a single unresectable brain metastasis with WBRT plus radiosurgery compared with WBRT alone; no evidence of improved survival in people with multiple brain metastasis)' categorised as Unknown effectiveness.
• Radiosurgery (stereotactic LINAC radiotherapy or gamma knife) New option. One systematic review found (search date 2004) which identified one RCT in abstract form now subsequently published in full, comparing radiosurgery versus whole-brain radiotherapy plus radiosurgery. One systematic review (search date 2004) foundwhich identified no RCTs comparing radiosurgery versus surgery. 'Radiosurgery (stereotactic LINAC radiotherapy or gamma knife)' categorised as Unknown effectiveness.

• Ablative neurosurgical techniques to the Gasserian ganglion (retrogasserian percutaneous radiofrequency thermocoagulation, glycerol rhizolysis, or balloon compression: New option for which we found no RCTs. Categorised as Unknown effectiveness, although there is some observational evidence suggesting that radiofrequency thermocoagulation may offer higher rates of complete pain relief than glycerol rhizolysis and stereotactic radiosurgery, although it is also associated with the highest rate of complications.

New evidence; conclusions changed for:

• Microvascular decompression New observational data and awareness of consensus that microvascular surgery is effective at reducing symptoms in the long term, although it can lead to ipsilateral hearing loss, led to change of categorisation to Trade-off between benefits and harms (based on consensus).

• Different Methods of bone fixation One RCT addedcomparing percutaneous Kirschner-wire fixation with internal screw fixation following distal chevron osteotomy found no significant differences between functional status or radiological findings at 6 months' follow-up.Categorisation unchanged (Unknown effectiveness).
• Distal metatarsal osteotomy Two subsequent RCTs added: One RCT comparing Lindgren osteotomy with distal chevron osteotomy found significant improvements in radiological outcomes with Lindgren osteotomy compared with distal chevron osteotomy after 1 year and 3–6 years' follow-up. The second RCT comparing scarf osteotomy with distal chevron osteotomy found no significant difference in functional status or radiological outcomes between groups at 2 years' follow-up.Categorisation unchanged (Likely to be beneficial).

• Dexamethasone (oral) versus prednisolone (oral) in children with moderate to severe croup One RCT added comparing prednisolone versus dexamethasone 0.6 mg/kg versus dexamethasone 0.15 mg/kg, all given orally. It found no significant difference among the groups in hospital admission or in the need for further medical attention. Categorisation changed (Unknown effectiveness).

New evidence; conclusion confirmed for:

• Dexamethasone (oral), higher dose versus lower dose in children with moderate to severe croup One RCT added comparing dexamethasone 0.6 mg/kg versus dexamethasone 0.15 mg/kg versus prednisolone, all given orally. It found no significant difference among the groups in hospital admission or in the need for further medical attention. Condition restructured: separated from Dexamethasone (im) v dexamethasone (oral). Categorisation unchanged (Unknown effectiveness).

• Refeeding Two systematic reviews added, which both identified the same RCT of zinc previously reported in this review. No new data added. Categorisation unchanged (Likely to be beneficial).
• Inpatient versus outpatient treatment setting Two systematic reviews added which both identified the same RCT previously reported in this review. No new data added. Categorisation unchanged (Unknown effectiveness).
• Psychotherapy Two systematic reviews added, which identified RCTs previously reported in this review. No new data added. One already included systematic review updated with new seach date of 2005. No new data added. One RCT comparing CBT plus placebo versus fluoxetine plus CBT added. This study had a high withdrawal rate, which limits the conclusions that can be drawn. Categorisation unchanged (Unknown effectiveness).
• SSRIs Three systematic reviews added, which did not pool data, and which identified three RCTs comparing fluoxetine or citalopram versus placebo which were previously reported in this review. No new data added from the reviews. One RCT comparing fluoxetine plus CBT versus placebo plus CBT added which had a high withdrawal rate which limited any conclusions that could be drawn. Categorisation unchanged (Unknown effectiveness).
• Anxiolytic drugs (benzodiazepines, older-generation antipsychotics, atypical antipsychotics) No new RCTs added to the benefits or harms sections. One small RCT (not meeting Clinical Evidence inclusion criteria for this review), controlled trials, and observational data on atypical antipsychotics added to the comment section as background data.
• Tricyclic antidepressants Three systematic reviews added. The reviews did not pool data, and identified two RCTs comparing amitriptyline versus placebo which were already reported in this review. No new data added. Categorisation unchanged (Likely to be ineffective or harmful).
• Oestrogen treatment Two systematic reviews added, which identified the same RCT previously reported in this review. No new data added. One subsequent RCT added, which found no significant difference between a triphasic oral contraceptive and placebo in bone mineral density after 13 cycles.Categorisation unchanged (Unknown effectiveness).