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Background: TNF (tumor necrosis factor)-alpha inhibitors block a key protein in the inflammatory chain reaction responsible for joint inflammation, pain, and damage in ankylosing spondylitis., Objectives: To assess the benefit and harms of adalimumab, etanercept, golimumab, and infliximab (TNF-alpha inhibitors) in people with ankylosing spondylitis., Search Methods: We searched the following databases to January 26, 2009: MEDLINE (from 1966); EMBASE (from 1980); the Cochrane Central Register of Controlled Trials (CENTRAL; 2008, Issue 4); ACP Journal Club; CINAHL (from 1982); and ISI Web of Knowledge (from 1900). We ran updated searches in May 2012, October 2013, and in June 2014 for McMaster PLUS. We searched major regulatory agencies for safety warnings and clinicaltrials.gov for registered trials., Selection Criteria: Randomized controlled trials (RCTs) comparing adalimumab, etanercept, golimumab and infliximab to placebo, other drugs or usual care in patients with ankylosing spondylitis, reported in abstract or full-text., Data Collection and Analysis: Two authors independently assessed search results, risk of bias, and extracted data. We conducted Bayesian mixed treatment comparison (MTC) meta-analyses using WinBUGS software. To investigate a class-effect of harms across biologics, we pooled harms data using Review Manager 5., Main Results: We included twenty-one, short-term (24 weeks or less) RCTs with a total of 3308 participants; 18 contributed data to the MTC analysis: adalimumab (4 studies), etanercept (8 studies), golimumab (2 studies), infliximab (3 studies), and one head-to-head study (etanercept versus infliximab) which was unblinded and considered at a higher risk of bias. The risk of selection and detection bias was low or unclear for most of the studies. The risk of selective outcome reporting was low for most studies as they reported on outcomes recommended by the Assessment of SpondyloArthritis international Society. We found little heterogeneity and no significant inconsistency in the MTC analyses. The majority of the studies were funded by pharmaceutical companies. Most studies permitted concomitant therapy of stable doses of disease-modifying anti-rheumatic drugs, non-steroidal anti-inflammatory drugs, or corticosteroids, but allowances varied across studies.Compared with placebo, there was high quality evidence that patients on an anti-TNF agent were three to four times more likely to achieve an ASAS40 response (assessing spinal pain, function, and inflammation, as measured by the mean of intensity and duration of morning stiffness, and patient global assessment) by six months (adalimumab: risk ratio (RR) 3.53, 95% credible interval (Crl) 2.49 to 4.91; etanercept: RR 3.31, 95% Crl 2.38 to 4.53; golimumab: RR 2.90, 95% Crl 1.90 to 4.23; infliximab: RR 4.07, 95% Crl 2.80 to 5.74, with a 25% to 40% absolute difference between treatment and placebo groups. The number needed to treat (NNT) to achieve an ASAS 40 response ranged from 3 to 5.There was high quality evidence of improvement in physical function on a 0 to 10 scale (adalimumab: mean difference (MD) -1.6, 95% Crl -2.2 to -0.9; etanercept: MD -1.1, 95% CrI -1.6 to -0.6; golimumab: MD -1.5, 95% Crl -2.3 to -0.7; infliximab: MD -2.1, 95% Crl -2.7 to -1.4, with an 11% to 21% absolute difference between treatment and placebo groups. The NNT to achieve the minimally clinically important difference of 0.7 points ranged from 2 to 4.Compared with placebo, there was moderate quality evidence (downgraded for imprecision) that patients on an anti-TNF agent were more likely to achieve an ASAS partial remission by six months (adalimumab: RR 6.28, 95% Crl 3.13 to 12.78; etanercept: RR 4.24, 95% Crl 2.31 to 8.09; golimumab: RR 5.18, 95% Crl 1.90 to 14.79; infliximab: RR 15.41, 95% Crl 5.09 to 47.98 with a 10% to 44% absolute difference between treatment and placebo groups. The NNT to achieve an ASAS partial remission response ranged from 3 to 11.There was low to moderate level evidence of a greater reduction in spinal inflammation as measured by magnetic resonance imaging though the absolute differences were small and the clinical relevance of the difference was unclear: adalimumab (1 trial; -6% (95% confidence interval (CI) -12% to 0.05%); 1 trial: 53.6% mean decrease from baseline versus 9.4% mean increase in the placebo group), golimumab (1 trial; -2.5%, (95% CI -5.6% to -0.7%)), and infliximab (1 trial; -3% (95% CI -4% to -2.4%)).Radiographic progression was measured in one trial (N = 60) of etanercept versus placebo and it found that radiologic changes were similar in both groups (detailed data not provided).There were few events of withdrawals due to adverse events leading to imprecision around the estimates. When all the anti-TNF agents were combined against placebo, there was moderate quality evidence from 16 studies of an increased risk of withdrawals due to adverse events in the anti-TNF group (Peto odds ratio (OR) 2.44, 95% CI 1.26 to 4.72; total events: 38/1637 in biologic group; 7/986 in placebo) though the absolute increase in harm was small (1%; 95% CI 0% to 2%).Due to low event rates, evidence of the effect of individual TNF-inhibitors against placebo or for all four biologics pooled together versus placebo on serious adverse events is inconclusive (moderate quality; downgraded for imprecision). For all anti-TNF pooled versus placebo based on 16 studies: Peto OR 1.45, 95% CI 0.85 to 2.48; 51/1530 in biologic group; 18/878 in placebo; absolute difference: 1% (95% CI 0% to 2%).Using indirect comparison methodology, and one head-to-head study of etanercept versus infliximab, wide confidence intervals meant that results were inconclusive for evidence of differences in the major outcomes between different anti-TNF agents. Regulatory agencies have published warnings about rare adverse events of serious infections, including tuberculosis, malignancies and lymphoma., Authors' Conclusions: There is moderate to high quality evidence that anti-TNF agents improve clinical symptoms in the treatment of ankylosing spondylitis. More participants withdrew due to adverse events when on an anti-TNF agent but we did not find evidence of an increase in serious adverse events, though event rates were low and trials had a short duration. The short-term toxicity profile appears acceptable. Based on indirect comparison methodology, we are uncertain whether there are differences between anti-TNF agents in terms of the key benefit or harm outcomes.

Background: Undernutrition contributes to five million deaths of children under five each year. Furthermore, throughout the life cycle, undernutrition contributes to increased risk of infection, poor cognitive functioning, chronic disease, and mortality. It is thus important for decision-makers to have evidence about the effectiveness of nutrition interventions for young children., Objectives: Primary objective1. To assess the effectiveness of supplementary feeding interventions, alone or with co-intervention, for improving the physical and psychosocial health of disadvantaged children aged three months to five years.Secondary objectives1. To assess the potential of such programmes to reduce socio-economic inequalities in undernutrition.2. To evaluate implementation and to understand how this may impact on outcomes.3. To determine whether there are any adverse effects of supplementary feeding., Search Methods: We searched CENTRAL, Ovid MEDLINE, PsycINFO, and seven other databases for all available years up to January 2014. We also searched ClinicalTrials.gov and several sources of grey literature. In addition, we searched the reference lists of relevant articles and reviews, and asked experts in the area about ongoing and unpublished trials., Selection Criteria: Randomised controlled trials (RCTs), cluster-RCTs, controlled clinical trials (CCTs), controlled before-and-after studies (CBAs), and interrupted time series (ITS) that provided supplementary food (with or without co-intervention) to children aged three months to five years, from all countries. Adjunctive treatments, such as nutrition education, were allowed. Controls had to be untreated., Data Collection and Analysis: Two or more review authors independently reviewed searches, selected studies for inclusion or exclusion, extracted data, and assessed risk of bias. We conducted meta-analyses for continuous data using the mean difference (MD) or the standardised mean difference (SMD) with a 95% confidence interval (CI), correcting for clustering if necessary. We analysed studies from low- and middle-income countries and from high-income countries separately, and RCTs separately from CBAs. We conducted a process evaluation to understand which factors impact on effectiveness., Main Results: We included 32 studies (21 RCTs and 11 CBAs); 26 of these (16 RCTs and 10 CBAs) were in meta-analyses. More than 50% of the RCTs were judged to have low risk of bias for random selection and incomplete outcome assessment. We judged most RCTS to be unclear for allocation concealment, blinding of outcome assessment, and selective outcome reporting. Because children and parents knew that they were given food, we judged blinding of participants and personnel to be at high risk for all studies.Growth. Supplementary feeding had positive effects on growth in low- and middle-income countries. Meta-analysis of the RCTs showed that supplemented children gained an average of 0.12 kg more than controls over six months (95% confidence interval (CI) 0.05 to 0.18, 9 trials, 1057 participants, moderate quality evidence). In the CBAs, the effect was similar; 0.24 kg over a year (95% CI 0.09 to 0.39, 1784 participants, very low quality evidence). In high-income countries, one RCT found no difference in weight, but in a CBA with 116 Aboriginal children in Australia, the effect on weight was 0.95 kg (95% CI 0.58 to 1.33). For height, meta-analysis of nine RCTs revealed that supplemented children grew an average of 0.27 cm more over six months than those who were not supplemented (95% CI 0.07 to 0.48, 1463 participants, moderate quality evidence). Meta-analysis of seven CBAs showed no evidence of an effect (mean difference (MD) 0.52 cm, 95% CI -0.07 to 1.10, 7 trials, 1782 participants, very low quality evidence). Meta-analyses of the RCTs demonstrated benefits for weight-for-age z-scores (WAZ) (MD 0.15, 95% CI 0.05 to 0.24, 8 trials, 1565 participants, moderate quality evidence), and height-for-age z-scores (HAZ) (MD 0.15, 95% CI 0.06 to 0.24, 9 trials, 4638 participants, moderate quality evidence), but not for weight-for-height z-scores MD 0.10 (95% CI -0.02 to 0.22, 7 trials, 4176 participants, moderate quality evidence). Meta-analyses of the CBAs showed no effects on WAZ, HAZ, or WHZ (very low quality evidence). We found moderate positive effects for haemoglobin (SMD 0.49, 95% CI 0.07 to 0.91, 5 trials, 300 participants) in a meta-analysis of the RCTs.Psychosocial outcomes. Eight RCTs in low- and middle-income countries assessed psychosocial outcomes. Our meta-analysis of two studies showed moderate positive effects of feeding on psychomotor development (SMD 0.41, 95% CI 0.10 to 0.72, 178 participants). The evidence of effects on cognitive development was sparse and mixed.We found evidence of substantial leakage. When feeding was given at home, children benefited from only 36% of the energy in the supplement. However, when the supplementary food was given in day cares or feeding centres, there was less leakage; children took in 85% of the energy provided in the supplement. Supplementary food was generally more effective for younger children (less than two years of age) and for those who were poorer/ less well-nourished. Results for sex were equivocal. Our results also suggested that feeding programmes which were given in day-care/feeding centres and those which provided a moderate-to-high proportion of the recommended daily intake (% RDI) for energy were more effective., Authors' Conclusions: Feeding programmes for young children in low- and middle-income countries can work, but good implementation is key.

Introduction: Tackling health inequities both within and between countries remains high on the agenda of international organizations including the World Health Organization and local, regional and national governments. Systematic reviews can be a useful tool to assess effects on equity in health status because they include studies conducted in a variety of settings and populations. This study aims to describe the extent to which the impacts of health interventions on equity in health status are considered in systematic reviews, describe methods used, and assess the implications of their equity related findings for policy, practice and research., Methods: We conducted a methodology study of equity assessment in systematic reviews. Two independent reviewers extracted information on the reporting and analysis of impacts of health interventions on equity in health status in a group of 300 systematic reviews collected from all systematic reviews indexed in one month of MEDLINE, using a pre-tested data collection form. Any differences in data extraction were resolved by discussion., Results: Of the 300 systematic reviews, 224 assessed the effectiveness of interventions on health outcomes. Of these 224 reviews, 29 systematic reviews assessed effects on equity in health status using subgroup analysis or targeted analyses of vulnerable populations. Of these, seven conducted subgroup analyses related to health equity which were reported in insufficient detail to judge their credibility. Of these 29 reviews, 18 described implications for policy and practice based on assessment of effects on health equity., Conclusion: The quality and completeness of reporting should be enhanced as a priority, because without this policymakers and practitioners will continue lack the evidence base they need to inform decision-making about health inequity. Furthermore, there is a need to develop methods to systematically consider impacts on equity in health status that is currently lacking in systematic reviews.

Background: Enhancing health equity has now achieved international political importance with endorsement from the World Health Assembly in 2009.  The failure of systematic reviews to consider effects on health equity is cited by decision-makers as a limitation to their ability to inform policy and program decisions. , Objectives: To systematically review methods to assess effects on health equity in systematic reviews of effectiveness., Search Strategy: We searched the following databases up to July 2 2010: MEDLINE, PsychINFO, the Cochrane Methodology Register, CINAHL, Education Resources Information Center, Education Abstracts, Criminal Justice Abstracts, Index to Legal Periodicals, PAIS International, Social Services Abstracts, Sociological Abstracts, Digital Dissertations and the Health Technology Assessment Database. We searched SCOPUS to identify articles that cited any of the included studies on October 7 2010., Selection Criteria: We included empirical studies of cohorts of systematic reviews that assessed methods for measuring effects on health inequalities., Data Collection and Analysis: Data were extracted using a pre-tested form by two independent reviewers. Risk of bias was appraised for included studies according to the potential for bias in selection and detection of systematic reviews. , Main Results: Thirty-four methodological studies were included.  The methods used by these included studies were: 1) Targeted approaches (n=22); 2) gap approaches (n=12) and gradient approach (n=1).  Gender or sex was assessed in eight out of 34 studies, socioeconomic status in ten studies, race/ethnicity in seven studies, age in seven studies, low and middle income countries in 14 studies, and two studies assessed multiple factors across health inequity may exist.Only three studies provided a definition of health equity. Four methodological approaches to assessing effects on health equity were identified: 1) descriptive assessment of reporting and analysis in systematic reviews (all 34 studies used a type of descriptive method); 2) descriptive assessment of reporting and analysis in original trials (12/34 studies); 3) analytic approaches (10/34 studies); and 4) applicability assessment (11/34 studies). Both analytic and applicability approaches were not reported transparently nor in sufficient detail to judge their credibility., Authors' Conclusions: There is a need for improvement in conceptual clarity about the definition of health equity, describing sufficient detail about analytic approaches (including subgroup analyses) and transparent reporting of judgments required for applicability assessments in order to assess and report effects on health equity in systematic reviews.