Showing papers in "Cochrane Database of Systematic Reviews in 2010"

Lay health workers in primary and community health care for maternal and child health and the management of infectious diseases.

Abstract: Background Lay health workers (LHWs) are widely used to provide care for a broad range of health issues. Little is known, however, about the effectiveness of LHW interventions. Objectives To assess the effects of LHW interventions in primary and community health care on maternal and child health and the management of infectious diseases. Search methods For the current version of this review we searched The Cochrane Central Register of Controlled Trials (including citations uploaded from the EPOC and the CCRG registers) (The Cochrane Library 2009, Issue 1 Online) (searched 18 February 2009); MEDLINE, Ovid (1950 to February Week 1 2009) (searched 17 February 2009); MEDLINE In-Process & Other Non-Indexed Citations, Ovid (February 13 2009) (searched 17 February 2009); EMBASE, Ovid (1980 to 2009 Week 05) (searched 18 February 2009); AMED, Ovid (1985 to February 2009) (searched 19 February 2009); British Nursing Index and Archive, Ovid (1985 to February 2009) (searched 17 February 2009); CINAHL, Ebsco 1981 to present (searched 07 February 2010); POPLINE (searched 25 February 2009); WHOLIS (searched 16 April 2009); Science Citation Index and Social Sciences Citation Index (ISI Web of Science) (1975 to present) (searched 10 August 2006 and 10 February 2010). We also searched the reference lists of all included papers and relevant reviews, and contacted study authors and researchers in the field for additional papers. Selection criteria Randomised controlled trials of any intervention delivered by LHWs (paid or voluntary) in primary or community health care and intended to improve maternal or child health or the management of infectious diseases. A 'lay health worker' was defined as any health worker carrying out functions related to healthcare delivery, trained in some way in the context of the intervention, and having no formal professional or paraprofessional certificate or tertiary education degree. There were no restrictions on care recipients. Data collection and analysis Two review authors independently extracted data using a standard form and assessed risk of bias. Studies that compared broadly similar types of interventions were grouped together. Where feasible, the study results were combined and an overall estimate of effect obtained. Main results Eighty-two studies met the inclusion criteria. These showed considerable diversity in the targeted health issue and the aims, content, and outcomes of interventions. The majority were conducted in high income countries (n = 55) but many of these focused on low income and minority populations. The diversity of included studies limited meta-analysis to outcomes for four study groups. These analyses found evidence of moderate quality of the effectiveness of LHWs in promoting immunisation childhood uptake (RR 1.22, 95% CI 1.10 to 1.37; P = 0.0004); promoting initiation of breastfeeding (RR = 1.36, 95% CI 1.14 to 1.61; P < 0.00001), any breastfeeding (RR 1.24, 95% CI 1.10 to 1.39; P = 0.0004), and exclusive breastfeeding (RR 2.78, 95% CI 1.74 to 4.44; P <0.0001); and improving pulmonary TB cure rates (RR 1.22 (95% CI 1.13 to 1.31) P <0.0001), when compared to usual care. There was moderate quality evidence that LHW support had little or no effect on TB preventive treatment completion (RR 1.00, 95% CI 0.92 to 1.09; P = 0.99). There was also low quality evidence that LHWs may reduce child morbidity (RR 0.86, 95% CI 0.75 to 0.99; P = 0.03) and child (RR 0.75, 95% CI 0.55 to 1.03; P = 0.07) and neonatal (RR 0.76, 95% CI 0.57 to 1.02; P = 0.07) mortality, and increase the likelihood of seeking care for childhood illness (RR 1.33, 95% CI 0.86 to 2.05; P = 0.20). For other health issues, the evidence is insufficient to draw conclusions regarding effectiveness, or to enable the identification of specific LHW training or intervention strategies likely to be most effective. Authors' conclusions LHWs provide promising benefits in promoting immunisation uptake and breastfeeding, improving TB treatment outcomes, and reducing child morbidity and mortality when compared to usual care. For other health issues, evidence is insufficient to draw conclusions about the effects of LHWs.

Laparoscopic versus open surgery for suspected appendicitis

Abstract: Background Laparoscopic surgery for acute appendicitis has been proposed to have advantages over conventional surgery. Objectives To compare the diagnostic and therapeutic effects of laparoscopic and conventional 'open' surgery. Search methods We searched the Cochrane Library, MEDLINE, EMBASE, LILACS, CNKI, SciSearch, study registries, and the congress proceedings of endoscopic surgical societies. Selection criteria We included randomized clinical trials comparing laparoscopic (LA) versus open appendectomy (OA) in adults or children. Studies comparing immediate OA versus diagnostic laparoscopy (followed by LA or OA if necessary) were separately identified. Data collection and analysis Two reviewers independently assessed trial quality. Missing information or data was requested from the authors. We used odds ratios (OR), relative risks (RR), and 95% confidence intervals (CI) for analysis. Main results We included 67 studies, of which 56 compared LA (with or without diagnostic laparoscopy) vs. OA in adults. Wound infections were less likely after LA than after OA (OR 0.43; CI 0.34 to 0.54), but the incidence of intraabdominal abscesses was increased (OR 1.87; CI 1.19 to 2.93). The duration of surgery was 10 minutes (CI 6 to 15) longer for LA. Pain on day 1 after surgery was reduced after LA by 8 mm (CI 5 to 11 mm) on a 100 mm visual analogue scale. Hospital stay was shortened by 1.1 day (CI 0.7 to 1.5). Return to normal activity, work, and sport occurred earlier after LA than after OA. While the operation costs of LA were significantly higher, the costs outside hospital were reduced. Seven studies on children were included, but the results do not seem to be much different when compared to adults. Diagnostic laparoscopy reduced the risk of a negative appendectomy, but this effect was stronger in fertile women (RR 0.20; CI 0.11 to 0.34) as compared to unselected adults (RR 0.37; CI 0.13 to 1.01). Authors' conclusions In those clinical settings where surgical expertise and equipment are available and affordable, diagnostic laparoscopy and LA (either in combination or separately) seem to have various advantages over OA. Some of the clinical effects of LA, however, are small and of limited clinical relevance. In spite of the mediocre quality of the available research data, we would generally recommend to use laparoscopy and LA in patients with suspected appendicitis unless laparoscopy itself is contraindicated or not feasible. Especially young female, obese, and employed patients seem to benefit from LA.

Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus

Abstract: Background Metformin is an oral anti-hyperglycemic agent that has been shown to reduce total mortality compared to other anti-hyperglycemic agents, in the treatment of type 2 diabetes mellitus. Metformin, however, is thought to increase the risk of lactic acidosis, and has been considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. Objectives To assess the incidence of fatal and nonfatal lactic acidosis, and to evaluate blood lactate levels, for those on metformin treatment compared to placebo or non-metformin therapies. Search strategy A comprehensive search was performed of electronic databases to identify studies of metformin treatment. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Selection criteria Prospective trials and observational cohort studies in patients with type 2 diabetes of least one month duration were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Data collection and analysis The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years, for metformin treatment and for non-metformin treatments. The upper limit for the true incidence of cases was calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed-effect model for continuous data. Main results Pooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 70,490 patient-years of metformin use or in 55,451 patients-years in the non-metformin group. Using Poisson statistics the upper limit for the true incidence of lactic acidosis per 100,000 patient-years was 4.3 cases in the metformin group and 5.4 cases in the non-metformin group. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to non-metformin therapies. Authors' conclusions There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments.

Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes

Abstract: Strategies to implement change in health professional performance have variable impact. A potential explanation is that the barriers to implementation are different in different settings and at different times. Change may be more likely if the strategies were specifically chosen to address the identified barriers. Objectives To assess the effectiveness of strategies tailored to address specific, identified barriers to change in professional performance. The authors included 15 studies. For Comparison 1 (an intervention tailored to address identified barriers to change compared to no intervention or an intervention(s) not tailored to the barriers), there was no consistency in the results and the effect sizes varied both across and within studies. A meta-regression of a subset of the included studies, using a classical approach estimated a combined OR of 2.18 (95% CI: 1.09, 4.34), p = 0.026 in favour of tailored interventions. However, when a Bayesian approach was taken, meta-regression gave a combined OR of 2.27 (95% Credible Interval: 0.92, 4.75), which was not statistically significant.

Interventions for preventing falls in older people in nursing care facilities and hospitals

Abstract: Background Falls in nursing care facilities and hospitals are common events that cause considerable morbidity and mortality for older people. Objectives To assess the effectiveness of interventions designed to reduce falls by older people in nursing care facilities and hospitals. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (January 2009); the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 2); MEDLINE, EMBASE, and CINAHL (all to November 2008); trial registers and reference lists of articles. Selection criteria Randomised controlled trials of interventions to reduce falls in older people in nursing care facilities or hospitals. Primary outcomes were rate of falls and risk of falling. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Data were pooled where appropriate. Main results We included 41 trials (25,422 participants). In nursing care facilities, the results from seven trials testing supervised exercise interventions were inconsistent. This was the case too for multifactorial interventions, which overall did not significantly reduce the rate of falls (rate ratio (RaR) 0.82, 95% CI 0.62 to 1.08; 7 trials, 2997 participants) or risk of falling (risk ratio (RR) 0.93, 95% CI 0.86 to 1.01; 8 trials, 3271 participants). A post hoc subgroup analysis, however, indicated that where provided by a multidisciplinary team, multifactorial interventions reduced the rate of falls (RaR 0.60, 95% CI 0.51 to 0.72; 4 trials, 1651 participants) and risk of falling (RR 0.85, 95% CI 0.77 to 0.95; 5 trials, 1925 participants). Vitamin D supplementation reduced the rate of falls (RaR 0.72, 95% CI 0.55 to 0.95; 4 trials, 4512 participants), but not risk of falling (RR 0.98, 95% CI 0.89 to 1.09; 5 trials, 5095 participants). In hospitals, multifactorial interventions reduced the rate of falls (RaR 0.69, 95% CI 0.49 to 0.96; 4 trials, 6478 participants) and risk of falling (RR 0.73, 95% CI 0.56 to 0.96; 3 trials, 4824 participants). Supervised exercise interventions showed a significant reduction in risk of falling (RR 0.44, 95% CI 0.20 to 0.97; 3 trials, 131 participants). Authors' conclusions There is evidence that multifactorial interventions reduce falls and risk of falling in hospitals and may do so in nursing care facilities. Vitamin D supplementation is effective in reducing the rate of falls in nursing care facilities. Exercise in subacute hospital settings appears effective but its effectiveness in nursing care facilities remains uncertain.

Family intervention for schizophrenia

Abstract: Background People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. Objectives To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. Search methods We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). Selection criteria We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. Data collection and analysis We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). Main results This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. Authors' conclusions Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality. Further data from trials that describe the methods of randomisation, test the blindness of the study evaluators, and implement the CONSORT guidelines would enable greater confidence in these findings.

Long‐term opioid management for chronic noncancer pain

Abstract: Background Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term effectiveness and safety, particularly the risk of tolerance, dependence, or abuse. Objectives To assess safety, efficacy, and effectiveness of opioids taken long-term for CNCP. Search methods We searched 10 bibliographic databases up to May 2009. Selection criteria We searched for studies that: collected efficacy data on participants after at least 6 months of treatment; were full-text articles; did not include redundant data; were prospective; enrolled at least 10 participants; reported data of participants who had CNCP. Randomized controlled trials (RCTs) and pre-post case-series studies were included. Data collection and analysis Two review authors independently extracted safety and effectiveness data and settled discrepancies by consensus. We used random-effects meta-analysis' to summarize data where appropriate, used the I2 statistic to quantify heterogeneity, and, where appropriate, explored heterogeneity using meta-regression. Several sensitivity analyses were performed to test the robustness of the results. Main results We reviewed 26 studies with 27 treatment groups that enrolled a total of 4893 participants. Twenty five of the studies were case series or uncontrolled long-term trial continuations, the other was an RCT comparing two opioids. Opioids were administered orally (number of study treatments groups [abbreviated as "k"] = 12, n = 3040), transdermally (k = 5, n = 1628), or intrathecally (k = 10, n = 231). Many participants discontinued due to adverse effects (oral: 22.9% [95% confidence interval (CI): 15.3% to 32.8%]; transdermal: 12.1% [95% CI: 4.9% to 27.0%]; intrathecal: 8.9% [95% CI: 4.0% to 26.1%]); or insufficient pain relief (oral: 10.3% [95% CI: 7.6% to 13.9%]; intrathecal: 7.6% [95% CI: 3.7% to 14.8%]; transdermal: 5.8% [95% CI: 4.2% to 7.9%]). Signs of opioid addiction were reported in 0.27% of participants in the studies that reported that outcome. All three modes of administration were associated with clinically significant reductions in pain, but the amount of pain relief varied among studies. Findings regarding quality of life and functional status were inconclusive due to an insufficient quantity of evidence for oral administration studies and inconclusive statistical findings for transdermal and intrathecal administration studies. Authors' conclusions Many patients discontinue long-term opioid therapy (especially oral opioids) due to adverse events or insufficient pain relief; however, weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief. Whether quality of life or functioning improves is inconclusive. Many minor adverse events (like nausea and headache) occurred, but serious adverse events, including iatrogenic opioid addiction, were rare.

Clinical pathways: effects on professional practice, patient outcomes, length of stay and hospital costs

Abstract: Background Clinical pathways are structured multidisciplinary care plans used by health services to detail essential steps in the care of patients with a specific clinical problem. They aim to link evidence to practice and optimise clinical outcomes whilst maximising clinical efficiency. Objectives To assess the effect of clinical pathways on professional practice, patient outcomes, length of stay and hospital costs. Search methods We searched the Database of Abstracts of Reviews of Effectiveness (DARE), the Effective Practice and Organisation of Care (EPOC) Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and bibliographic databases including MEDLINE, EMBASE, CINAHL, NHS EED and Global Health. We also searched the reference lists of relevant articles and contacted relevant professional organisations. Selection criteria Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series studies comparing stand alone clinical pathways with usual care as well as clinical pathways as part of a multifaceted intervention with usual care. Data collection and analysis Two review authors independently screened all titles to assess eligibility and methodological quality. Studies were grouped into those comparing clinical pathways with usual care and those comparing clinical pathways as part of a multifaceted intervention with usual care. Main results Twenty-seven studies involving 11,398 participants met the eligibility and study quality criteria for inclusion. Twenty studies compared stand alone clinical pathways with usual care. These studies indicated a reduction in in-hospital complications (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.36 to 0.94) and improved documentation (OR 11.95: 95%CI 4.72 to 30.30). There was no evidence of differences in readmission to hospital or in-hospital mortality. Length of stay was the most commonly employed outcome measure with most studies reporting significant reductions. A decrease in hospital costs/ charges was also observed, ranging from WMD +261 US$ favouring usual care to WMD -4919 US$ favouring clinical pathways (in US$ dollar standardized to the year 2000). Considerable heterogeneity prevented meta-analysis of length of stay and hospital cost results. An assessment of whether lower hospital costs contributed to cost shifting to another health sector was not undertaken. Seven studies compared clinical pathways as part of a multifaceted intervention with usual care. No evidence of differences were found between intervention and control groups. Authors' conclusions Clinical pathways are associated with reduced in-hospital complications and improved documentation without negatively impacting on length of stay and hospital costs.

Interventions used to improve control of blood pressure in patients with hypertension.

Abstract: Background Patients with high blood pressure (hypertension) in the community frequently fail to meet treatment goals - a condition labelled as "uncontrolled" hypertension. The optimal way to organize and deliver care to hypertensive patients has not been clearly identified. Objectives To determine the effectiveness of interventions to improve control of blood pressure in patients with hypertension. To evaluate the effectiveness of reminders on improving the follow-up of patients with hypertension. Search methods All-language search of all articles (any year) in the Cochrane Controlled Trials Register (CCTR) and Medline; and Embase from January 1980. Selection criteria Randomized controlled trials (RCTs) of patients with hypertension that evaluated the following interventions: (1) self-monitoring (2) educational interventions directed to the patient (3) educational interventions directed to the health professional (4) health professional (nurse or pharmacist) led care (5) organisational interventions that aimed to improve the delivery of care (6) appointment reminder systems Outcomes assessed were: (1) mean systolic and diastolic blood pressure (2) control of blood pressure (3) proportion of patients followed up at clinic Data collection and analysis Two authors extracted data independently and in duplicate and assessed each study according to the criteria outlined by the Cochrane Handbook. Main results 72 RCTs met our inclusion criteria. The methodological quality of included studies varied. An organized system of regular review allied to vigorous antihypertensive drug therapy was shown to reduce systolic blood pressure (weighted mean difference (WMD) -8.0 mmHg, 95% CI: -8.8 to -7.2 mmHg) and diastolic blood pressure (WMD -4.3 mmHg, 95% CI: -4.7 to -3.9 mmHg) for three strata of entry blood pressure, and all-cause mortality at five years follow-up (6.4% versus 7.8%, difference 1.4%) in a single large RCT- the Hypertension Detection and Follow-Up study. Other interventions had variable effects. Self-monitoring was associated with moderate net reduction in systolic blood pressure (WMD -2.5 mmHg, 95% CI: -3.7 to -1.3 mmHg) and diastolic blood pressure (WMD -1.8 mmHg, 95% CI: -2.4 to -1.2 mmHg). RCTs of educational interventions directed at patients or health professionals were heterogeneous but appeared unlikely to be associated with large net reductions in blood pressure by themselves. Nurse or pharmacist led care may be a promising way forward, with the majority of RCTs being associated with improved blood pressure control and mean SBP and DBP but these interventions require further evaluation. Appointment reminder systems also require further evaluation due to heterogeneity and small trial numbers, but the majority of trials increased the proportion of individuals who attended for follow-up (odds ratio 0.41, 95% CI 0.32 to 0.51) and in two small trials also led to improved blood pressure control, odds ratio favouring intervention 0.54 (95% CI 0.41 to 0.73). Authors' conclusions Family practices and community-based clinics need to have an organized system of regular follow-up and review of their hypertensive patients. Antihypertensive drug therapy should be implemented by means of a vigorous stepped care approach when patients do not reach target blood pressure levels. Self-monitoring and appointment reminders may be useful adjuncts to the above strategies to improve blood pressure control but require further evaluation.

Interventions for treating oral mucositis for patients with cancer receiving treatment.

Abstract: BACKGROUND: Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers). OBJECTIVES: To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment. SEARCH STRATEGY: Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 16 February 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 16 February 2011), EMBASE via OVID (1980 to 16 February 2011), CINAHL via EBSCO (1980 to 16 February 2011), CANCERLIT via PubMed (1950 to 16 February 2011), OpenSIGLE (1980 to 2005) and LILACS via the Virtual Health Library (1980 to 16 February 2011) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Randomised controlled trials of interventions to prevent oral mucositis in patients receiving treatment for cancer. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions, outcome measures, results and risk of bias were independently extracted, in duplicate, by two review authors. Authors were contacted for further details where these were unclear. The Cochrane Collaboration statistical guidelines were followed and risk ratios calculated using random-effects models. MAIN RESULTS: A total of 131 studies with 10,514 randomised participants are now included. Overall only 8% of these studies were assessed as being at low risk of bias. Ten interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These ten interventions were: aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate. AUTHORS' CONCLUSIONS: Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.

Opioid antagonists for alcohol dependence

Abstract: Alcohol dependence belongs to the globally leading health risk factors Therapeutic success of psychosocial programs for relapse prevention is moderate and could be increased by an adjuvant treatment with the opioid antagonists naltrexone and nalmefene The objective of this review is to determine the effectiveness and tolerability of opioid antagonists in the treatment of alcohol dependence

Vaccines for preventing influenza in the elderly

Abstract: Background Vaccines have been the main global weapon to minimise the impact of influenza in the elderly for the last four decades and are recommended worldwide for individuals aged 65 years or older The primary goal of influenza vaccination in the elderly is to reduce the risk of complications among persons who are most vulnerable Objectives To assess the effectiveness of vaccines in preventing influenza, influenza-like illness (ILI), hospital admissions, complications and mortality in the elderly To identify and appraise comparative studies evaluating the effects of influenza vaccines in the elderly To document types and frequency of adverse effects associated with influenza vaccines in the elderly Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register (The Cochrane Library 2009, issue 4); MEDLINE (January 1966 to October Week 1 2009); EMBASE (1974 to October 2009) and Web of Science (1974 to October 2009) Selection criteria Randomised controlled trials (RCTs), quasi-RCTs, cohort and case-control studies assessing efficacy against influenza (laboratory-confirmed cases) or effectiveness against influenza-like illness (ILI) or safety Any influenza vaccine given independently, in any dose, preparation or time schedule, compared with placebo or with no intervention was considered Data collection and analysis We grouped reports first according to the setting of the study (community or long-term care facilities) and then by level of viral circulation and vaccine matching We further stratified by co-administration of pneumococcal polysaccharide vaccine (PPV) and by different types of influenza vaccines We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications and deaths Main results We included 75 studies Overall we identified 100 data sets We identified one RCT assessing efficacy and effectiveness Although this seemed to show an effect against influenza symptoms it was underpowered to detect any effect on complications (1348 participants) The remainder of our evidence base included non-RCTs Due to the general low quality of non-RCTs and the likely presence of biases, which make interpretation of these data difficult and any firm conclusions potentially misleading, we were unable to reach clear conclusions about the effects of the vaccines in the elderly Authors' conclusions The available evidence is of poor quality and provides no guidance regarding the safety, efficacy or effectiveness of influenza vaccines for people aged 65 years or older To resolve the uncertainty, an adequately powered publicly-funded randomised, placebo-controlled trial run over several seasons should be undertaken

Behavioural treatment for chronic low-back pain

Abstract: BACKGROUND: Behavioural treatment, commonly used in the treatment of chronic low-back pain (CLBP), is primarily focused at reducing disability through the modification of environmental contingencies and cognitive processes. In general, three behavioural treatment approaches are distinguished: operant, cognitive and respondent. OBJECTIVES: To determine if behavioural therapy is more effective than reference treatments for CLBP, and which type of behavioural treatment is most effective. SEARCH STRATEGY: We searched the CENTRAL, MEDLINE, EMBASE, and PsycLIT databases up to October 2003. References of identified randomised trials and relevant systematic reviews were screened. SELECTION CRITERIA: Only randomised trials on behavioural treatment for non-specific CLBP were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality and extracted the data. The magnitude of effect was assessed by computing a pooled effect size for post-treatment and long-term results for each comparison, for each domain (i.e., behavioural outcomes, overall improvement, back pain specific and generic functional status, return to work, and pain intensity) using the random effects model. MAIN RESULTS: Seven studies (33%) were considered high quality. Comparing behavioural treatment to waiting list control (WLC) revealed strong evidence (4 trials, 134 people) in favour of a combined respondent-cognitive therapy for a medium positive effect on pain, and moderate evidence (2 trials, 39 people) in favour of progressive relaxation for a large positive effect on pain and behavioural outcomes (short-term only). When comparing operant treatment to WLC no significant differences could be detected on general functional status (strong evidence: 2 trials, 87 people) or on behavioural outcomes (moderate evidence; 3 trials, 153 people) (short-term only). There is limited evidence (1 trial, 98 people) that a graded activity program in an industrial setting is more effective than usual care for early return to work and reduced long-term sick leave. There is limited evidence (1 trail, 39 people) that there are no differences between behavioural treatment and exercises. Finally, there is moderate evidence (6 trials, 210 people) that there are no significant differences in short-term and long-term effectiveness when behavioural components are added to usual treatment programs for CLBP (i.e. physiotherapy, back education) on pain, generic functional status and behavioural outcomes. AUTHORS' CONCLUSIONS: Combined respondent-cognitive therapy and progressive relaxation therapy are more effective than WLC on short-term pain relief. However, it is unknown whether these results sustain in the long term. No significant differences could be detected between behavioural treatment and exercise therapy. Whether clinicians should refer patients with CLBP to behavioural treatment programs or to active conservative treatment cannot be concluded from this review.

Treatment of latent tuberculosis infection in HIV infected persons

Abstract: Background Individuals with human immunodeficiency virus (HIV) infection are at an increased risk of developing active tuberculosis (TB). It is known that treatment of latent TB infection (LTBI), also referred to as TB preventive therapy or chemoprophylaxis, helps to prevent progression to active disease in HIV negative populations. However, the extent and magnitude of protection (if any) associated with preventive therapy in those infected with HIV should be quantified. This present study is an update of the original review. Objectives To determine the effectiveness of TB preventive therapy in reducing the risk of active tuberculosis and death in HIV-infected persons. Search methods This review was updated using the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, AIDSLINE, AIDSTRIALS, AIDSearch, NLM Gateway and AIDSDRUGS (publication date from 01 July 2002 to 04 April 2008). We also scanned reference lists of articles and contacted authors and other researchers in the field in an attempt to identify additional studies that may be eligible for inclusion in this review. Selection criteria We included randomized controlled trials in which HIV positive individuals were randomly allocated to TB preventive therapy or placebo, or to alternative TB preventive therapy regimens. Participants could be tuberculin skin test positive or negative, but without active tuberculosis. Data collection and analysis Three reviewers independently applied the study selection criteria, assessed study quality and extracted data. Effects were assessed using relative risk for dichotomous data and mean differences for continuous data. Main results 12 trials were included with a total of 8578 randomized participants. TB preventive therapy (any anti-TB drug) versus placebo was associated with a lower incidence of active TB (RR 0.68, 95% CI 0.54 to 0.85). This benefit was more pronounced in individuals with a positive tuberculin skin test (RR 0.38, 95% CI 0.25 to 0.57) than in those who had a negative test (RR 0.89, 95% CI 0.64 to 1.24). Efficacy was similar for all regimens (regardless of drug type, frequency or duration of treatment). However, compared to INH monotherapy, short-course multi-drug regimens were much more likely to require discontinuation of treatment due to adverse effects. Although there was reduction in mortality with INH monotherapy versus placebo among individuals with a positive tuberculin skin test (RR 0.74, 95% CI 0.55 to 1.00) and with INH plus rifampicin versus placebo regardless of tuberculin skin test status (RR 0.69, 95% CI 0.50 to 0.95), overall, there was no evidence that TB preventive therapy versus placebo reduced all-cause mortality (RR 0.94, 95% CI 0.85 to 1.05). Authors' conclusions Treatment of latent tuberculosis infection reduces the risk of active TB in HIV positive individuals especially in those with a positive tuberculin skin test. The choice of regimen will depend on factors such as availability, cost, adverse effects, adherence and drug resistance. Future studies should assess these aspects. In addition, trials evaluating the long-term effects of anti-tuberculosis chemoprophylaxis, the optimal duration of TB preventive therapy, the influence of level of immunocompromise on effectiveness and combination of anti-tuberculosis chemoprophylaxis with antiretroviral therapy are needed.

Structured telephone support or telemonitoring programmes for patients with chronic heart failure

Abstract: Background Specialised disease management programmes for chronic heart failure (CHF) improve survival, quality of life and reduce healthcare utilisation. The overall efficacy of structured telephone support or telemonitoring as an individual component of a CHF disease management strategy remains inconclusive. Objectives To review randomised controlled trials (RCTs) of structured telephone support or telemonitoring compared to standard practice for patients with CHF in order to quantify the effects of these interventions over and above usual care for these patients. Search methods Databases (the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment Database (HTA) on The Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED and Science Citation Index Expanded and Conference Citation Index on ISI Web of Knowledge) and various search engines were searched from 2006 to November 2008 to update a previously published non-Cochrane review. Bibliographies of relevant studies and systematic reviews and abstract conference proceedings were handsearched. No language limits were applied. Selection criteria Only peer reviewed, published RCTs comparing structured telephone support or telemonitoring to usual care of CHF patients were included. Unpublished abstract data was included in sensitivity analyses. The intervention or usual care could not include a home visit or more than the usual (four to six weeks) clinic follow-up. Data collection and analysis Data were presented as risk ratio (RR) with 95% confidence intervals (CI). Primary outcomes included all-cause mortality, all-cause and CHF-related hospitalisations which were meta-analysed using fixed effects models. Other outcomes included length of stay, quality of life, acceptability and cost and these were described and tabulated. Main results Twenty-five studies and five published abstracts were included. Of the 25 full peer-reviewed studies meta-analysed, 16 evaluated structured telephone support (5613 participants), 11 evaluated telemonitoring (2710 participants), and two tested both interventions (included in counts). Telemonitoring reduced all-cause mortality (RR 0.66, 95% CI 0.54 to 0.81, P < 0.0001) with structured telephone support demonstrating a non-significant positive effect (RR 0.88, 95% CI 0.76 to 1.01, P = 0.08). Both structured telephone support (RR 0.77, 95% CI 0.68 to 0.87, P < 0.0001) and telemonitoring (RR 0.79, 95% CI 0.67 to 0.94, P = 0.008) reduced CHF-related hospitalisations. For both interventions, several studies improved quality of life, reduced healthcare costs and were acceptable to patients. Improvements in prescribing, patient knowledge and self-care, and New York Heart Association (NYHA) functional class were observed. Authors' conclusions Structured telephone support and telemonitoring are effective in reducing the risk of all-cause mortality and CHF-related hospitalisations in patients with CHF; they improve quality of life, reduce costs, and evidence-based prescribing.

Fluoride toothpastes of different concentrations for preventing dental caries in children and adolescents

Abstract: Background Caries (dental decay) is a disease of the hard tissues of the teeth caused by an imbalance, over time, in the interactions between cariogenic bacteria in dental plaque and fermentable carbohydrates (mainly sugars). The use of fluoride toothpaste is the primary intervention for the prevention of caries. Objectives To determine the relative effectiveness of fluoride toothpastes of different concentrations in preventing dental caries in children and adolescents, and to examine the potentially modifying effects of baseline caries level and supervised toothbrushing. Search methods A search was undertaken on Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and several other databases. Reference lists of articles were also searched. Date of the most recent searches: 8 June 2009. Selection criteria Randomised controlled trials and cluster-randomised controlled trials comparing fluoride toothpaste with placebo or fluoride toothpaste of a different concentration in children up to 16 years of age with a follow-up period of at least 1 year. The primary outcome was caries increment in the permanent or deciduous dentition as measured by the change in decayed, (missing), filled tooth surfaces (D(M)FS/d(m)fs) from baseline. Data collection and analysis Inclusion of studies, data extraction and quality assessment were undertaken independently and in duplicate by two members of the review team. Disagreements were resolved by discussion and consensus or by a third party. The primary effect measure was the prevented fraction (PF), the caries increment of the control group minus the caries increment of the treatment group, expressed as a proportion of the caries increment in the control group. Where it was appropriate to pool data, network meta-analysis, network meta-regression or meta-analysis models were used. Potential sources of heterogeneity were specified a priori and examined through random-effects meta-regression analysis where appropriate. Main results 75 studies were included, of which 71 studies comprising 79 trials contributed data to the network meta-analysis, network meta-regression or meta-analysis. For the 66 studies (74 trials) that contributed to the network meta-analysis of D(M)FS in the mixed or permanent dentition, the caries preventive effect of fluoride toothpaste increased significantly with higher fluoride concentrations (D(M)FS PF compared to placebo was 23% (95% credible interval (CrI) 19% to 27%) for 1000/1055/1100/1250 parts per million (ppm) concentrations rising to 36% (95% CrI 27% to 44%) for toothpastes with a concentration of 2400/2500/2800 ppm), but concentrations of 440/500/550 ppm and below showed no statistically significant effect when compared to placebo. There is some evidence of a dose response relationship in that the PF increased as the fluoride concentration increased from the baseline although this was not always statistically significant. The effect of fluoride toothpaste also increased with baseline level of D(M)FS and supervised brushing, though this did not reach statistical significance. Six studies assessed the effects of fluoride concentrations on the deciduous dentition with equivocal results dependent upon the fluoride concentrations compared and the outcome measure. Compliance with treatment regimen and unwanted effects was assessed in only a minority of studies. When reported, no differential compliance was observed and unwanted effects such as soft tissue damage and tooth staining were minimal. Authors' conclusions This review confirms the benefits of using fluoride toothpaste in preventing caries in children and adolescents when compared to placebo, but only significantly for fluoride concentrations of 1000 ppm and above. The relative caries preventive effects of fluoride toothpastes of different concentrations increase with higher fluoride concentration. The decision of what fluoride levels to use for children under 6 years should be balanced with the risk of fluorosis.

Placebo interventions for all clinical conditions.

Abstract: Background Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment Two previous versions of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain Since then several relevant trials have been published Objectives Our primary aims were to assess the effect of placebo interventions in general across all clinical conditions, and to investigate the effects of placebo interventions on specific clinical conditions Our secondary aims were to assess whether the effect of placebo treatments differed for patient-reported and observer-reported outcomes, and to explore other reasons for variations in effect Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 4, 2007), MEDLINE (1966 to March 2008), EMBASE (1980 to March 2008), PsycINFO (1887 to March 2008) and Biological Abstracts (1986 to March 2008) We contacted experts on placebo research, and read references in the included trials Selection criteria We included randomised placebo trials with a no-treatment control group investigating any health problem Data collection and analysis Two authors independently assessed trial quality and extracted data We contacted study authors for additional information Trials with binary data were summarised using relative risk (a value of less than 1 indicates a beneficial effect of placebo), and trials with continuous outcomes were summarised using standardised mean difference (a negative value indicates a beneficial effect of placebo) Main results Outcome data were available in 202 out of 234 included trials, investigating 60 clinical conditions We regarded the risk of bias as low in only 16 trials (8%), five of which had binary outcomes In 44 studies with binary outcomes (6041 patients), there was moderate heterogeneity (P < 0001; I2 45%) but no clear difference in effects between small and large trials (symmetrical funnel plot) The overall pooled effect of placebo was a relative risk of 093 (95% confidence interval (CI) 088 to 099) The pooled relative risk for patient-reported outcomes was 093 (95% CI 086 to 100) and for observer-reported outcomes 093 (95% CI 085 to 102) We found no statistically significant effect of placebo interventions in four clinical conditions that had been investigated in three trials or more: pain, nausea, smoking, and depression, but confidence intervals were wide The effect on pain varied considerably, even among trials with low risk of bias In 158 trials with continuous outcomes (10,525 patients), there was moderate heterogeneity (P < 0001; I2 42%), and considerable variation in effects between small and large trials (asymmetrical funnel plot) It is therefore a questionable procedure to pool all the trials, and we did so mainly as a basis for exploring causes for heterogeneity We found an overall effect of placebo treatments, standardised mean difference (SMD) -023 (95% CI -028 to -017) The SMD for patient-reported outcomes was -026 (95% CI -032 to -019), and for observer-reported outcomes, SMD -013 (95% CI -024 to -002) We found an effect on pain, SMD -028 (95% CI -036 to -019)); nausea, SMD -025 (-046 to -004)), asthma (-035 (-070 to -001)), and phobia (SMD -063 (95% CI -117 to -008)) The effect on pain was very variable, also among trials with low risk of bias Four similarly-designed acupuncture trials conducted by an overlapping group of authors reported large effects (SMD -068 (-085 to -050)) whereas three other pain trials reported low or no effect (SMD -013 (-028 to 003)) The pooled effect on nausea was small, but consistent The effects on phobia and asthma were very uncertain due to high risk of bias There was no statistically significant effect of placebo interventions in the seven other clinical conditions investigated in three trials or more: smoking, dementia, depression, obesity, hypertension, insomnia and anxiety, but confidence intervals were wide Meta-regression analyses showed that larger effects of placebo interventions were associated with physical placebo interventions (eg sham acupuncture), patient-involved outcomes (patient-reported outcomes and observer-reported outcomes involving patient cooperation), small trials, and trials with the explicit purpose of studying placebo Larger effects of placebo were also found in trials that did not inform patients about the possible placebo intervention Authors' conclusions We did not find that placebo interventions have important clinical effects in general However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed

Gamma and other cephalocondylic intramedullary nails versus extramedullary implants for extracapsular hip fractures in adults

Abstract: Background Cephalocondylic intramedullary nails which are inserted proximally to distally (cephalocondylic) have been used for the surgical treatment of extracapsular hip fractures. Objectives To compare all cephalocondylic intramedullary nails with extramedullary implants for the surgical treatment of extracapsular hip fractures in adults. This is the third update of our original review which compared the Gamma nail with the sliding hip screw (SHS). Search strategy We searched the Cochrane Musculoskeletal Injuries Group trials register, MEDLINE, select orthopaedic journals and conference proceedings, and reference lists of relevant articles. We contacted trialists, colleagues and implant manufacturers. Date of the most recent search: August 2001. Selection criteria All randomised and quasi-randomised trials comparing cephalocondylic nails with extramedullary implants for extracapsular hip fractures. Data collection and analysis Both reviewers independently assessed trial quality and extracted data. Additional information was sought from all trialists. Wherever appropriate and possible, results were pooled. Main results The one trial of 230 patients comparing the Kuntscher-Y nail with the SHS, reported no major difference the outcome aside from a significantly increased number of patients with leg shortening, and a tendency for poorer recovery of mobility in the Kuntscher-Y nail group. Seventeen trials comparing the Gamma nail with the SHS were included, with data available for 2472 patients. The Gamma nail was associated with an increased risk of operative and later fracture of the femur and an increased re-operation rate. There were no major differences in the incidence of wound infection, mortality or medical complications between implants. Data were inadequate to determine if there were differences for other outcomes. Five trials involving 603 patients compared the intramedullary hip screw (IMHS) with the SHS. Fracture fixation complications were more common in the IMHS group: all cases of operative and later fracture of the femur occurred in this group. Results for post-operative complications, mortality and functional outcomes were similar in the two groups. Two under-reported trials tested the proximal femoral nail (PFN). The results of one study of 206 patients with a trochanteric fracture showed no advantages for the PFN compared with the SHS. The other study, involving 39 patients, comparing the PFN with the dynamic condylar plate for treating more distal and uncommon trochanteric fractures gave better intra-operative and fracture fixation results for the PFN. One trial of 60 patients reported favourable preliminary results for an experimental mini-invasive static intramedullary nail compared with the SHS. Reviewer's conclusions Further evidence is required before any conclusions can be drawn on the relative merits of either the Kuntscher-Y nail or the mini-invasive static intramedullary nail in comparison with the SHS. Given the lower complication rate of the SHS in comparison with intramedullary nails, it appears that for trochanteric fractures the SHS is superior. Further studies will be required to determine if different types of intramedullary nail produce the same results, or if intramedullary nails have advantages for selected fracture types, for example, reversed fracture lines and subtrochanteric fractures. From the evidence available, IMHS appears to have the same problems as the Gamma nail, but other theoretical advantages of the IHMS cannot be ruled out.

Vaginal misoprostol for cervical ripening and induction of labour

Abstract: Background Misoprostol (Cytotec, Searle) is a prostaglandin E1 analogue widely used for off-label indications such as induction of abortion and of labour. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. Objectives To determine the effects of vaginal misoprostol for third trimester cervical ripening or induction of labour. Search methods The Cochrane Pregnancy and Childbirth Group's Trials Register (November 2008) and bibliographies of relevant papers. We updated this search on 15 February 2012 and added the results to the awaiting classification section. Selection criteria Clinical trials comparing vaginal misoprostol used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. Data collection and analysis We developed a strategy to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. We used fixed-effect Mantel-Haenszel meta-analysis for combining dichotomous data. If we identified substantial heterogeneity (I² greater than 50%), we used a random-effects method. Main results We included 121 trials. The risk of bias must be kept in mind as only 13 trials were double blind. Compared to placebo, misoprostol was associated with reduced failure to achieve vaginal delivery within 24 hours (average relative risk (RR) 0.51, 95% confidence interval (CI) 0.37 to 0.71). Uterine hyperstimulation, without fetal heart rate (FHR) changes, was increased (RR 3.52 95% CI 1.78 to 6.99). Compared with vaginal prostaglandin E2, intracervical prostaglandin E2 and oxytocin, vaginal misoprostol was associated with less epidural analgesia use, fewer failures to achieve vaginal delivery within 24 hours and more uterine hyperstimulation. Compared with vaginal or intracervical prostaglandin E2, oxytocin augmentation was less common with misoprostol and meconium-stained liquor more common. Lower doses of misoprostol compared to higher doses were associated with more need for oxytocin augmentation and less uterine hyperstimulation, with and without FHR changes. We found no information on women's views. Authors' conclusions Vaginal misoprostol in doses above 25 mcg four-hourly was more effective than conventional methods of labour induction, but with more uterine hyperstimulation. Lower doses (25 mcg four-hourly or less) were similar to conventional methods in effectiveness and risks. The authors request information on cases of uterine rupture known to readers. The vaginal route should not be researched further as another Cochrane review has shown that the oral route of administration is preferable to the vaginal route. Professional and governmental bodies should agree guidelines for the use of misoprostol, based on the best available evidence and local circumstances. [Note: The 27 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]

Sublingual immunotherapy for allergic rhinitis

Abstract: Background Allergic rhinitis is a common condition which, at its most severe, can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids. Allergen injection immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions. There has therefore been considerable interest in alternative routes for delivery of allergen immunotherapy, particularly the sublingual route. Objectives To evaluate the efficacy of sublingual immunotherapy (SLIT), compared with placebo, for reductions in symptoms and medication requirements. Search strategy The Cochrane Controlled Trials Register, MEDLINE (1966 to 2002), EMBASE (1974 to 2002) and SciSearch were searched, up to September 2002, using the terms (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). Selection criteria All studies identified by the searches were assessed by the reviewers to identify randomised controlled trials involving participants with symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT or corresponding placebo. Data collection and analysis Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.1. Analysis was performed by the method of Standardised Mean Differences (SMD) using a random-effects model. P values < 0.05 were considered statistically significant. Subgroup analyses were performed according to the type of allergen administered, the age of participants and the duration of treatment. Main results Twenty-two trials involving 979 patients were included. There were six trials of SLIT for house dust mite allergy, five for grass pollen, five for Parietaria, two for olive and one each for ragweed, cat, tree and Cupressus. Five studies enrolled exclusively children. Seventeen studies administered the allergen by sublingual drops subsequently swallowed, three by drops subsequently spat out and two by sublingual tablets. Eight studies involved treatment for less than six months, 10 studies for 6 to 12 months and four studies for greater than 12 months. All included studies were double-blind placebo-controlled trials of parallel group design. Concealment of treatment allocation was considered adequate in all studies and the use of identical placebo preparations was almost universal. There was significant heterogeneity, most likely due to widely differing scoring systems between studies, for most comparisons. Overall there was a significant reduction in both symptoms (SMD -0.42, 95% confidence interval -0.69 to -0.15; p = 0.002) and medication requirements (SMD -0.43 [-0.63, -0.23]; p = 0.00003) following immunotherapy. Subgroup analyses failed to identify a disproportionate benefit of treatment according to the allergen administered. There was no significant reduction in symptoms and medication scores in those studies involving only children but total numbers of participants were too small to make this a reliable conclusion. Increasing duration of treatment does not clearly increase efficacy. The total dose of allergen administered may be important but insufficient data were available to analyse this factor. Authors' conclusions SLIT is a safe treatment which significantly reduces symptoms and medication requirements in allergic rhinitis. The size of this benefit compared to that of other available therapies, particularly injection immunotherapy, is not clear, having been assessed directly in very few studies. Further research is required concentrating on optimising allergen dosage and patient selection.

Probiotics for treating acute infectious diarrhoea

Abstract: Background Probiotics may be effective in reducing the duration of acute infectious diarrhoea. Objectives To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. Search methods We searched the trials register of the Cochrane Infectious Diseases Group, MEDLINE, and Embase from inception to 17 December 2019, as well as the Cochrane Controlled Trials Register (Issue 12, 2019), in the Cochrane Library, and reference lists from studies and reviews. We included additional studies identified during external review. Selection criteria Randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. Data collection and analysis Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data. Primary outcomes were measures of diarrhoea duration (diarrhoea lasting ≥ 48 hours; duration of diarrhoea). Secondary outcomes were number of people hospitalized in community studies, duration of hospitalization in inpatient studies, diarrhoea lasting ≥ 14 days, and adverse events. Main results We included 82 studies with a total of 12,127 participants. These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group). No cluster‐randomized trials were included. Studies varied in the definitions used for "acute diarrhoea" and "end of the diarrhoeal illness" and in the probiotic(s) tested. A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high. Risk of bias was high or unclear in many studies, and there was marked statistical heterogeneity when findings for the primary outcomes were pooled in meta‐analysis. Effect size was similar in the sensitivity analysis and marked heterogeneity persisted. Publication bias was demonstrated from funnel plots for the main outcomes. In our main analysis of the primary outcomes in studies at low risk for all indices of risk of bias, no difference was detected between probiotic and control groups for the risk of diarrhoea lasting ≥ 48 hours (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.91 to 1.09; 2 trials, 1770 participants; moderate‐certainty evidence); or for duration of diarrhoea (mean difference (MD) 8.64 hours shorter, 95% CI 29.4 hours shorter to 12.1 hours longer; 6 trials, 3058 participants; very low‐certainty evidence). Effect size was similar and marked heterogeneity persisted in pre‐specified subgroup analyses of the primary outcomes that included all studies. These included analyses limited to the probiotics Lactobacillus rhamnosus GG and Saccharomyces boulardii. In six trials (433 participants) of Lactobacillus reuteri, there was consistency amongst findings (I² = 0%), but risk of bias was present in all included studies. Heterogeneity also was not explained by types of participants (age, nutritional/socioeconomic status captured by mortality stratum, region of the world where studies were undertaken), diarrhoea in children caused by rotavirus, exposure to antibiotics, and the few studies of children who were also treated with zinc. In addition, there were no clear differences in effect size for the primary outcomes in post hoc analyses according to decade of publication of studies and whether or not trials had been registered. For other outcomes, the duration of hospitalization in inpatient studies on average was shorter in probiotic groups than in control groups but there was marked heterogeneity between studies (I² = 96%; MD ‐18.03 hours, 95% CI ‐27.28 to ‐8.78, random‐effects model: 24 trials, 4056 participants). No differences were detected between probiotic and control groups in the number of people with diarrhoea lasting ≥ 14 days (RR 0.49, 95% CI 0.16 to 1.53; 9 studies, 2928 participants) or in risk of hospitalization in community studies (RR 1.26, 95% CI 0.84 to 1.89; 6 studies, 2283 participants). No serious adverse events were attributed to probiotics. Authors' conclusions Probiotics probably make little or no difference to the number of people who have diarrhoea lasting 48 hours or longer, and we are uncertain whether probiotics reduce the duration of diarrhoea. This analysis is based on large trials with low risk of bias.

Injection allergen immunotherapy for asthma.

Abstract: Background Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and methods of delivery, we updated the systematic review of allergen specific immunotherapy for asthma. Objectives The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. Search strategy We searched the Cochrane Airways Group Trials Register up to 2005, Dissertation Abstracts and Current Contents. Selection criteria Randomised controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome. Data collection and analysis Three authors independently assessed eligibility of studies for inclusion. Two authors independently performed quality assessment of studies. Main results Eighty-eight trials were included (13 new trials). There were 42 trials of immunotherapy for house mite allergy; 27 pollen allergy trials; 10 animal dander allergy trials; two Cladosporium mould allergy, two latex and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 16 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication, and improvement in bronchial hyper-reactivity following immunotherapy. There was a significant improvement in asthma symptom scores (standardised mean difference -0.59, 95% confidence interval -0.83 to -0.35) and it would have been necessary to treat three patients (95% CI 3 to 5) with immunotherapy to avoid one deterioration in asthma symptoms. Overall it would have been necessary to treat four patients (95% CI 3 to 6) with immunotherapy to avoid one requiring increased medication. Allergen immunotherapy significantly reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. If 16 patients were treated with immunotherapy, one would be expected to develop a local adverse reaction. If nine patients were treated with immunotherapy, one would be expected to develop a systemic reaction (of any severity). Authors' conclusions Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered.

Cell salvage for minimising perioperative allogeneic blood transfusion

Abstract: Background Concerns regarding the safety of transfused blood have prompted reconsideration of the use of allogeneic (from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques to minimise transfusion requirements. Objectives To examine the evidence for the efficacy of cell salvage in reducing allogeneic blood transfusion and the evidence for any effect on clinical outcomes. Search methods We identified studies by searching CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (1950 to June 2009), EMBASE (1980 to June 2009), the internet (to August 2009) and bibliographies of published articles. Selection criteria Randomised controlled trials with a concurrent control group in which adult patients, scheduled for non-urgent surgery, were randomised to cell salvage (autotransfusion) or to a control group who did not receive the intervention. Data collection and analysis Data were independently extracted and the risk of bias assessed. Relative risks (RR) and weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Data were pooled using a random-effects model. The primary outcomes were the number of patients exposed to allogeneic red cell transfusion and the amount of blood transfused. Other clinical outcomes are detailed in the review. Main results A total of 75 trials were included. Overall, the use of cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 38% (RR 0.62; 95% CI 0.55 to 0.70). The absolute reduction in risk (ARR) of receiving an allogeneic RBC transfusion was 21% (95% CI 15% to 26%). In orthopaedic procedures the RR of exposure to RBC transfusion was 0.46 (95% CI 0.37 to 0.57) compared to 0.77 (95% CI 0.69 to 0.86) for cardiac procedures. The use of cell salvage resulted in an average saving of 0.68 units of allogeneic RBC per patient (WMD -0.68; 95% CI -0.88 to -0.49). Cell salvage did not appear to impact adversely on clinical outcomes. Authors' conclusions The results suggest cell salvage is efficacious in reducing the need for allogeneic red cell transfusion in adult elective cardiac and orthopaedic surgery. The use of cell salvage did not appear to impact adversely on clinical outcomes. However, the methodological quality of trials was poor. As the trials were unblinded and lacked adequate concealment of treatment allocation, transfusion practices may have been influenced by knowledge of the patients' treatment status potentially biasing the results in favour of cell salvage.

Indoor residual spraying for preventing malaria

Abstract: BACKGROUND: Primary malaria prevention on a large scale depends on two vector control interventions: indoor residual spraying (IRS) and insecticide-treated mosquito nets (ITNs). Historically, IRS has reduced malaria transmission in many settings in the world, but the health effects of IRS have never been properly quantified. This is important, and will help compare IRS with other vector control interventions. OBJECTIVES: To quantify the impact of IRS alone, and to compare the relative impacts of IRS and ITNs, on key malariological parameters. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (September 2009), CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to September 2009), EMBASE (1974 to September 2009), LILACS (1982 to September 2009), mRCT (September 2009), reference lists, and conference abstracts. We also contacted researchers in the field, organizations, and manufacturers of insecticides (June 2007). SELECTION CRITERIA: Cluster randomized controlled trials (RCTs), controlled before-and-after studies (CBA) and interrupted time series (ITS) of IRS compared to no IRS or ITNs. Studies examining the impact of IRS on special groups not representative of the general population, or using insecticides and dosages not recommended by the World Health Organization (WHO) were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed trials for inclusion. Two authors extracted data, assessed risk of bias and analysed the data. Where possible, we adjusted confidence intervals (CIs) for clustering. Studies were grouped into those comparing IRS with no IRS, and IRS compared with ITNs, and then stratified by malaria endemicity. MAIN RESULTS: IRS versus no IRSStable malaria (entomological inoculation rate (EIR) 1): Two studies; for incidence and prevalence, the malaria rates were higher in the IRS group compared to the ITN group in one study. Malaria incidence was higher in the IRS arm in India (risk ratio IRS:ITN = 1.48) and in South Africa (risk ratio 1.34 but the cluster unadjusted CIs included 1). For malaria prevalence, ITNs appeared to give better protection against any infection compared to IRS in India (risk ratio IRS:ITN = 1.70) and also for both P. falciparum (risk ratio IRS:ITN = 1.78) and P. vivax (risk ratio IRS:ITN = 1.37). AUTHORS' CONCLUSIONS: Historical and programme documentation has clearly established the impact of IRS. However, the number of high-quality trials are too few to quantify the size of effect in different transmission settings. The evidence from randomized comparisons of IRS versus no IRS confirms that IRS reduces malaria incidence in unstable malaria settings, but randomized trial data from stable malaria settings is very limited. Some limited data suggest that ITN give better protection than IRS in unstable areas, but more trials are needed to compare the effects of ITNs with IRS, as well as to quantify their combined effects

Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism.

Abstract: Background Low molecular weight heparins (LMWHs) have been shown to be effective and safe in preventing venous thromboembolism (VTE). They may also be effective for the initial treatment of VTE. This is an update of a Cochrane review first published in 1999 and previously updated in 2004. Objectives To determine the effect of LMWH compared with unfractionated heparin (UFH) for the initial treatment of VTE. Search methods Trials were identified by searching the Cochrane Peripheral Vascular Diseases Group Specialised Register and CENTRAL (The Cochrane Library). Colleagues and pharmaceutical companies were contacted for additional information. Selection criteria Randomised controlled trials comparing fixed dose subcutaneous LMWH with adjusted dose intravenous or subcutaneous UFH in people with VTE. Data collection and analysis Two review authors assessed trials for inclusion and quality, and extracted data independently. Main results Twenty-three studies were included (n = 9587). Thrombotic complications occurred in 3.6% of participants treated with LMWH compared with 5.3% treated with UFH (odds ratio (OR) 0.70; 95% confidence interval (CI) 0.57 to 0.85). Thrombus size was reduced in 53% of participants treated with LMWH and 45% treated with UFH (OR 0.69; 95% CI 0.59 to 0.81). Major haemorrhages occurred in 1.1% of participants treated with LMWH compared with 1.9% treated with UFH (OR 0.58; 95% CI 0.40 to 0.83). In 19 trials, 4.3% of participants treated with LMWH died compared with 5.8% of participants treated with UFH (OR 0.77; 95% CI 0.63 to 0.93). Nine studies (n = 4451) examined proximal thrombosis, 2192 participants were treated with LMWH and 2259 with UFH. Subgroup analysis showed statistically significant reductions favouring LMWH in thrombotic complications and major haemorrhage. By end of follow up, 80 (3.6%) participants treated with LMWH had thrombotic complications compared with 143 (6.3%) treated with UFH (OR 0.57; 95% CI 0.44 to 0.75). Major haemorrhages occurred in 18 (1.0%) participants treated with LMWH compared with 37 (2.1%) treated with UFH (OR 0.50; 95% CI 0.29 to 0.85). Nine studies showed a statistically significant reduction in mortality favouring LMWH. By the end of follow up, 3.3% (70/2094) of participants treated with LMWH had died and 5.3% (110/2063) treated with UFH. Authors' conclusions Fixed dose LMWH is more effective and safer than adjusted dose UFH for the initial treatment of VTE. Compared to UFH, LMWH significantly reduced the incidence of thrombotic complications, the occurrence of major haemorrhage during initial treatment and overall mortality at follow up.

Concurrent chemoradiotherapy in non-small cell lung cancer.

Abstract: Background This is an updated version of the original review published in Issue 4, 2004. The use of concurrent chemotherapy and radiotherapy in non-small cell lung cancer (NSCLC) might be seen as a way of increasing the effectiveness of radical radiotherapy at the same time as reducing the risks of metastatic disease. Objectives To determine the effectiveness of concurrent chemoradiotherapy as compared to radiotherapy alone with regard to overall survival, tumour control and treatment-related morbidity. To determine the effectiveness of concurrent versus sequential chemoradiotherapy. Search methods For this update we ran a new search in October 2009, using a search strategy adapted from the design in the original review. We searched: CENTRAL (accessed through The Cochrane Library, 2009, Issue 4), MEDLINE (accessed through PubMed), and EMBASE (accessed through Ovid). Selection criteria Randomised trials of patients with stage I-III NSCLC undergoing radical radiotherapy and randomised to receive concurrent chemoradiotherapy versus radiotherapy alone, or concurrent versus sequential chemoradiotherapy. Data collection and analysis Study selection, data extraction and assessment of risk of bias was performed independently by two authors. Pooled hazard ratios and relative risks were calculated according to a random-effects model. Main results Nineteen randomised studies (2728 participants) of concurrent chemoradiotherapy versus radiotherapy alone were included. Chemoradiotherapy significantly reduced overall risk of death (HR 0.71, 95% CI 0.64 to 0.80; I2 0%; 1607 participants) and overall progression-free survival at any site (HR 0.69, 95% CI 0.58 to 0.81; I2 45%; 1145 participants). Incidence of acute oesophagitis, neutropenia and anaemia were significantly increased with concurrent chemoradiation. Six trials (1024 patients) of concurrent versus sequential chemoradiation were included. A significant benefit of concurrent treatment was shown in overall survival (HR 0.74, 95% CI 0.62 to 0.89; I2 0%; 702 participants). This represented a 10% absolute survival benefit at 2 years. More treatment-related deaths (4% vs 2%) were reported in the concurrent arm without statistical significance (RR 2.02, 95% CI 0.90 to 4.52; I2 0%; 950 participants). There was increased severe oesophagitis with concurrent treatment (RR 4.96, 95%CI 2.17 to 11.37; I2 66%; 947 participants). Authors' conclusions This update of the review published in 2004 incorporates additional trials and more mature data. It demonstrates the benefit of concurrent chemoradiation over radiotherapy alone or sequential chemoradiotherapy. Patient selection is an important consideration in view of the added toxicity of concurrent treatment. Uncertainty remains as to how far this is purely due to a radiosensitising effect and whether similar benefits could be achieved by using modern radiotherapy techniques and more dose intensive accelerated and/ or hyperfractionated radiotherapy regimens.

Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus

Abstract: Type 1 diabetes is a metabolic disorder resulting from a defect in insulin secretion. Onset of type 1 diabetes mellitus may occur at any age and it is one of the most common chronic diseases of childhood and adolescence. Since there are no interventions known to prevent onset, it is vital that effective treatment regimes are available. Glycaemic control is maintained by replacement of insulin and may be in the form of 'conventional' insulin therapy (multiple injections per day) or continuous subcutaneous insulin infusion (CSII). The objective of this review is to assess the effects of CSII compared to multiple insulin injections (MI) in people with type 1 diabetes mellitus.

Magnesium sulphate and other anticonvulsants for women with pre-eclampsia.

Abstract: Background Eclampsia, the occurrence of a seizure (fit) in association with pre-eclampsia, is rare but potentially life-threatening. Magnesium sulphate is the drug of choice for treating eclampsia. This review assesses its use for preventing eclampsia. Objectives To assess the effects of magnesium sulphate, and other anticonvulsants, for prevention of eclampsia. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (4 June 2010), and the Cochrane Central Register of Controlled Trials Register (The Cochrane Library 2010, Issue 3). Selection criteria Randomised trials comparing anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs, for pre-eclampsia. Data collection and analysis Two authors assessed trial quality and extracted data independently. Main results We included 15 trials. Six (11,444 women) compared magnesium sulphate with placebo or no anticonvulsant: magnesium sulphate more than a halved the risk of eclampsia (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; number needed to treat for an additional beneficial outcome (NNTB) 100, 95% CI 50 to 100), with a non-significant reduction in maternal death (RR 0.54, 95% CI 0.26 to 1.10) but no clear difference in serious maternal morbidity (RR 1.08, 95% CI 0.89 to 1.32). It reduced the risk of placental abruption (RR 0.64, 95% CI 0.50 to 0.83; NNTB 100, 95% CI 50 to 1000), and increased caesarean section (RR 1.05, 95% CI 1.01 to 1.10). There was no clear difference in stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15). Side effects, primarily flushing, were more common with magnesium sulphate (24% versus 5%; RR 5.26, 95% CI 4.59 to 6.03; number need to treat for an additional harmful outcome (NNTH) 6, 95% CI 5 to 6). Follow-up was reported by one trial comparing magnesium sulphate with placebo: for 3375 women there was no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53) or morbidity potentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26) (median follow-up 26 months); for 3283 children exposed in utero there was no clear difference in death (RR 1.02, 95% CI 0.57 to 1.84) or neurosensory disability (RR 0.77, 95% CI 0.38 to 1.58) at age 18 months. Magnesium sulphate reduced eclampsia compared to phenytoin (three trials, 2291 women; RR 0.08, 95% CI 0.01 to 0.60) and nimodipine (one trial, 1650 women; RR 0.33, 95% CI 0.14 to 0.77). Authors' conclusions Magnesium sulphate more than halves the risk of eclampsia, and probably reduces maternal death. There is no clear effect on outcome after discharge from hospital. A quarter of women report side effects with magnesium sulphate.

Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis.

Abstract: Background Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of prophylactic antibiotics raises concerns about antibiotic resistance and fungal infection. Objectives To determine the efficacy and safety of prophylactic antibiotics in acute pancreatitis complicated by CT proven pancreatic necrosis. Search methods Searches were updated in November 2008, in The Cochrane Library (Issue 2, 2008), MEDLINE, EMBASE, and CINAHL. Conference proceedings and references from found articles were also searched. Selection criteria Randomised controlled trials (RCTs) comparing antibiotics versus placebo in acute pancreatitis with CT proven necrosis. Data collection and analysis Primary outcomes were mortality and pancreatic infection rates. Secondary end-points included non pancreatic infection, all sites infection, operative rates, fungal infections, and antibiotic resistance. Subgroup analyses were performed for antibiotic regimen (beta-lactam, quinolone, and imipenem). Main results Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance. With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84). Authors' conclusions No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended.

Cognitive behavioural therapy for tinnitus

Abstract: Background Tinnitus affects up to 21% of the adult population with an estimated 1% to 3% experiencing severe problems. Cognitive behavioural therapy (CBT) is a collection of psychological treatments based on the cognitive and behavioural traditions in psychology and often used to treat people suffering from tinnitus. Objectives To assess the effects and safety of CBT for tinnitus in adults. Search methods The Cochrane ENT Information Specialist searched the ENT Trials Register; CENTRAL (2019, Issue 11); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 November 2019. Selection criteria Randomised controlled trials (RCTs) of CBT versus no intervention, audiological care, tinnitus retraining therapy or any other active treatment in adult participants with tinnitus. Data collection and analysis We used the standard methodological procedures expected by Cochrane. Our primary outcomes were the impact of tinnitus on disease-specific quality of life and serious adverse effects. Our secondary outcomes were: depression, anxiety, general health-related quality of life, negatively biased interpretations of tinnitus and other adverse effects. We used GRADE to assess the certainty of evidence for each outcome. Main results We included 28 studies (mostly from Europe) with a total of 2733 participants. All participants had had tinnitus for at least three months and their average age ranged from 43 to 70 years. The duration of the CBT ranged from 3 to 22 weeks and it was mostly conducted in hospitals or online. There were four comparisons and we were interested in outcomes at end of treatment, and 6 and 12 months follow-up. The results below only refer to outcomes at end of treatment due to an absence of evidence at the other follow-up time points. CBT versus no intervention/wait list control Fourteen studies compared CBT with no intervention/wait list control. For the primary outcome, CBT may reduce the impact of tinnitus on quality of life at treatment end (standardised mean difference (SMD) -0.56, 95% confidence interval (CI) -0.83 to -0.30; 10 studies; 537 participants; low certainty). Re-expressed as a score on the Tinnitus Handicap Inventory (THI; range 0 to 100) this is equivalent to a score 10.91 points tower in the CBT group, with an estimated minimal clinically important difference (MCID) for this scale being 7 points. Seven studies, rated as moderate certainty, either reported or informed us via personal commu nication about serious adverse effects. CBT probably results in little or no difference in adverse effects: six studies reported none and in one study one participant in the CBT condition worsened (risk ratio (RR) 3.00, 95% CI 0.13 to 69.87). For the secondary outcomes, CBT may result in a slight reduction in depression (SMD -0.34, 95% CI-0.60 to -0.08; 8 studies; 502 participants; low certainty). However, we are uncertain whether CBT reduces anxiety, improves health-related quality of life or reduces negatively biased interpretations of tinnitus (all very low certainty). From seven studies, no other adverse effects were reported (moderate certainty). CBT versus audiological care Three studies compared CBT with audiological care. CBT probably reduces the impact of tinnitus on quality of life when compared with audiological care as measured by the THI (range 0 to 100; mean difference (MD) -5.65, 95% CI -9.79 to -1.50; 3 studies; 444 participants) (moderate certainty; MCID = 7 points). No serious adverse effects occurred in the two included studies reporting these, thus risk ratios were not calculated (moderate certainty). The evidence suggests that CBT may slightly reduce depression but may result in little or no difference in anxiety or health-related quality of life (all low certainty) when compared with audiological care. CBT may reduce negatively biased interpretations of tinnitus when compared with audiological care (low certainty). No other adverse effects were reported for either group (moderate certainty). CBT versus tinnitus retraining therapy (TRT) One study compared CBT with TRT (including bilateral sound generators as per TRT protocol). CBT may reduce the impact of tinnitus on quality of life as measured by the THI when compared with TRT (range 0 to 100) (MD -15.79, 95% CI -27.91 to -3.67; 1 study; 42 participants; low certainty). For serious adverse effects three participants deteriorated during the study: one in the CBT (n = 22) and two in the TRT group (n = 20) (RR 0.45, 95% CI 0.04 to 4.64; low certainty). We are uncertain whether CBT reduces depression and anxiety or improves heal-threlated quality of life (low certainty). CBT may reduce negatively biased interpretations of tinnitus. No data were available for other adverse effects. CBT versus other active control Sixteen studies compared CBT with another active control (e.g. relaxation, information, Internet-based discussion forums). CBT may reduce the impact of tinnitus on quality of life when compared with other active treatments (SMD -0.30, 95% CI -0.55 to -0.05; 12 studies; 966 participants; low certainty). Re-expressed as a THI score this is equivalent to 5.84 points lower in the CBT group than the other active control group (MCID = 7 points). One study reported that three participants deteriorated: one in the CBT and two in the information only group (RR 1.70, 95% CI 0.16 to 18.36; low certainty). CBT may reduce depression and anxiety (both low certainty). We are uncertain whether CBT improves health-related quality of life compared with other control. CBT probably reduces negatively biased interpretations of tinnitus compared with other treatments. No data were available for other adverse effects. Authors' conclusions CBT may be effective in reducing the negative impact that tinnitus can have on quality of life. There is, however, an absence of evidence at 6 or 12 months follow-up. There is also some evidence that adverse effects may be rare in adults with tinnitus receiving CBT, but this could be further investigated. CBT fortinnitus may have small additional benefit in reducing symptoms of depression although uncertainty remains due to concerns about the quality of the evidence. Overall, there is limited evidence for CBT for tinnitus improving anxiety, heal-threlated quality of life or negatively biased interpretations of tinnitus.