Label-invariant models for the analysis of meta-epidemiological data.

Rich meta-epidemiological data sets have been collected to explore associations between intervention effect estimates and study-level characteristics. Welton et al proposed models for the analysis of meta-epidemiological data, but these models are restrictive because they force heterogeneity among studies with a particular characteristic to be at least as large as that among studies without the characteristic. In this paper we present alternative models that are invariant to the labels defining the 2 categories of studies. To exemplify the methods, we use a collection of meta-analyses in which the Cochrane Risk of Bias tool has been implemented. We first investigate the influence of small trial sample sizes (less than 100 participants), before investigating the influence of multiple methodological flaws (inadequate or unclear sequence generation, allocation concealment, and blinding). We fit both the Welton et al model and our proposed label-invariant model and compare the results. Estimates of mean bias associated with the trial characteristics and of between-trial variances are not very sensitive to the choice of model. Results from fitting a univariable model show that heterogeneity variance is, on average, 88% greater among trials with less than 100 participants. On the basis of a multivariable model, heterogeneity variance is, on average, 25% greater among trials with inadequate/unclear sequence generation, 51% greater among trials with inadequate/unclear blinding, and 23% lower among trials with inadequate/unclear allocation concealment, although the 95% intervals for these ratios are very wide. Our proposed label-invariant models for meta-epidemiological data analysis facilitate investigations of between-study heterogeneity attributable to certain study characteristics

Desorption of metals from Cetraria islandica (L.) Ach. Lichen using solutions simulating acid rain

Desorption of metals K, Al, Ca, Mg, Fe, Ba, Zn, Mn, Cu and Sr from Cetraria islandica (L.) with solutions whose composition was similar to that of acid rain, was investigated. Desorption of metals from the lichen was performed by five successive desorption processes. Solution mixtures containing H2SO4, HNO3 and H2SO4-HNO3 were used for desorption. Each solution had three different pH values: 4.61, 5.15 and 5.75, so that the desorptions were performed with nine different solutions successively five times, always using the same solution volume. The investigated metals can be divided into two groups. One group was comprised of K, Ca and Mg, which were desorbed in each of the five desorption processes at all pH values used. The second group included Al, Fe, Zn, Ba, Mn and Sr; these were not desorbed in each individual desorption and not at all pH values, whereas Cu was not desorbed at all under any circumstances. Using the logarithmic dependence of the metal content as a function of the desorption number, it was found that potassium builds two types of links and is connected with weaker links in lichen. Potassium is completely desorbed, 80% in the first desorption, and then gradually in the following desorptions. Other metals are linked with one weaker link (desorption 1-38%) and with one very strong link (desorption below the metal detection limit). [Projekat Ministarstva nauke Republike Srbije, br. III43009 i br. ON 172019

The effects of changes to the built environment on the mental health and well-being of adults: Systematic review

© 2018 The Authors There is increasing interest in the influence of place on health, and the need to distinguish between environmental and individual level factors. For environmental-level factors, current evidence tends to show associations through cross-sectional and uncontrolled longitudinal analyses rather than through more robust study designs that can provide stronger causal evidence. We restricted this systematic review to randomised (or cluster) randomised controlled trials and controlled before-and-after studies of changes to the built environment. Date of search was December 2016. We identified 14 studies. No evidence was found of an effect on mental health from ‘urban regeneration’ and ‘improving green infrastructure’ studies. Beneficial effects on quality-of-life outcomes from ‘improving green infrastructure’ were found in two studies. One ‘improving green infrastructure’ study reported an improvement in social isolation. Risk-of-bias assessment indicated robust data from only four studies. Overall, evidence for the impact of built environment interventions on mental health and quality-of-life is weak. Future research requires more robust study designs and interdisciplinary research involving public health, planning and urban design experts

Adjusting trial results for biases in meta-analysis: combining data-based evidence on bias with detailed trial assessment.

Flaws in the conduct of randomized trials can lead to biased estimation of the intervention effect. Methods for adjustment of within-trial biases in meta-analysis include the use of empirical evidence from an external collection of meta-analyses, and the use of expert opinion informed by the assessment of detailed trial information. Our aim is to present methods to combine these two approaches to gain the advantages of both. We make use of the risk of bias information that is routinely available in Cochrane reviews, by obtaining empirical distributions for the bias associated with particular bias profiles (combinations of risk of bias judgements). We propose three methods: a formal combination of empirical evidence and opinion in a Bayesian analysis; asking experts to give an opinion on bias informed by both summary trial information and a bias distribution from the empirical evidence, either numerically or by selecting areas of the empirical distribution. The methods are demonstrated through application to two example binary outcome meta-analyses. Bias distributions based on opinion informed by trial information alone were most dispersed on average, and those based on opinions obtained by selecting areas of the empirical distribution were narrowest. Although the three methods for combining empirical evidence with opinion vary in ease and speed of implementation, they yielded similar results in the two examples

Empirical evidence of study design biases in randomized trials:Systematic review of meta-epidemiological studies

To synthesise evidence on the average bias and heterogeneity associated with reported methodological features of randomized trials.Systematic review of meta-epidemiological studies.We retrieved eligible studies included in a recent AHRQ-EPC review on this topic (latest search September 2012), and searched Ovid MEDLINE and Ovid EMBASE for studies indexed from Jan 2012-May 2015. Data were extracted by one author and verified by another. We combined estimates of average bias (e.g. ratio of odds ratios (ROR) or difference in standardised mean differences (dSMD)) in meta-analyses using the random-effects model. Analyses were stratified by type of outcome ("mortality" versus "other objective" versus "subjective"). Direction of effect was standardised so that ROR < 1 and dSMD < 0 denotes a larger intervention effect estimate in trials with an inadequate or unclear (versus adequate) characteristic.We included 24 studies. The available evidence suggests that intervention effect estimates may be exaggerated in trials with inadequate/unclear (versus adequate) sequence generation (ROR 0.93, 95% CI 0.86 to 0.99; 7 studies) and allocation concealment (ROR 0.90, 95% CI 0.84 to 0.97; 7 studies). For these characteristics, the average bias appeared to be larger in trials of subjective outcomes compared with other objective outcomes. Also, intervention effects for subjective outcomes appear to be exaggerated in trials with lack of/unclear blinding of participants (versus blinding) (dSMD -0.37, 95% CI -0.77 to 0.04; 2 studies), lack of/unclear blinding of outcome assessors (ROR 0.64, 95% CI 0.43 to 0.96; 1 study) and lack of/unclear double blinding (ROR 0.77, 95% CI 0.61 to 0.93; 1 study). The influence of other characteristics (e.g. unblinded trial personnel, attrition) is unclear.Certain characteristics of randomized trials may exaggerate intervention effect estimates. The average bias appears to be greatest in trials of subjective outcomes. More research on several characteristics, particularly attrition and selective reporting, is needed

Agreement was moderate between data-based and opinion-based assessments of biases affecting randomised trials within meta-analyses

BACKGROUND: Randomised trials included in meta-analyses are often affected by bias caused by methodological flaws or limitations, but the degree of bias is unknown. Two proposed methods adjust trial results for bias using: (1) empirical evidence from published meta-epidemiological studies; or (2) expert opinion. METHODS: We investigated agreement between data-based and opinion-based approaches to assessing bias in each of four domains: sequence generation, allocation concealment, blinding and incomplete outcome data. From each sampled meta-analysis, a pair of trials with the highest and lowest empirical model-based bias estimates was selected. Independent assessors were asked which trial within each pair was judged more biased on the basis of detailed trial design summaries. RESULTS: Assessors judged trials to be equally biased in 68% of pairs evaluated. When assessors judged one trial as more biased, the proportion of judgements agreeing with the model-based ranking was highest for allocation concealment (79%) and blinding (79%) and lower for sequence generation (59%) and incomplete outcome data (56%). CONCLUSIONS: Most trial pairs found to be discrepant empirically were judged to be equally biased by assessors. We found moderate agreement between opinion and data-based evidence in pairs where assessors ranked one trial as more biased

Methodological overview of systematic reviews to establish the evidence base for emergency general surgery

BACKGROUND: The evidence for treatment decision‐making in emergency general surgery has not been summarized previously. The aim of this overview was to review the quantity and quality of systematic review evidence for the most common emergency surgical conditions. METHODS: Systematic reviews of the most common conditions requiring unplanned admission and treatment managed by general surgeons were eligible for inclusion. The Centre for Reviews and Dissemination databases were searched to April 2014. The number and type (randomized or non‐randomized) of included studies and patients were extracted and summarized. The total number of unique studies was recorded for each condition. The nature of the interventions (surgical, non‐surgical invasive or non‐invasive) was documented. The quality of reviews was assessed using the AMSTAR checklist. RESULTS: The 106 included reviews focused mainly on bowel conditions (42), appendicitis (40) and gallstone disease (17). Fifty‐one (48·1 per cent) included RCTs alone, 79 (74·5 per cent) included at least one RCT and 25 (23·6 per cent) summarized non‐randomized evidence alone. Reviews included 727 unique studies, of which 30·3 per cent were RCTs. Sixty‐five reviews compared different types of surgical intervention and 27 summarized trials of surgical versus non‐surgical interventions. Fifty‐seven reviews (53·8 per cent) were rated as low risk of bias. CONCLUSION: This overview of reviews highlights the need for more and better research in this field

Educational interventions to prevent paediatric abusive head trauma in babies younger than one year old: A systematic review and meta-analyses

AbstractBackgroundPaediatric abusive head trauma (AHT) occurs in young children due to violent shaking or blunt impact. Educational and behavioural programmes modifying parent/infant interactions may aid primary prevention. This systematic review aims to assess the effectiveness of such interventions to prevent AHT in infants.MethodsWe searched Embase, MEDLINE, PsycINFO, The Cochrane library, CINAHL databases and trial registries to September 2021, for studies assessing the effectiveness of educational and behavioural interventions in preventing AHT. Eligible interventions had to include messaging about avoiding or dangers of infant shaking. Randomised controlled trials (RCTs) reporting results for primary (AHT, infant shaking) or secondary outcomes (including parental responses to infant crying, mental wellbeing), and non-randomised studies (NRSs) reporting primary outcomes were included. Evidence from combinable studies was synthesised using random-effects meta-analyses. Certainty of evidence was assessed using GRADE framework. PROSPERO registration CRD42020195644.FindingsOf 25 identified studies, 16 were included in meta-analyses. Five NRSs reported results for AHT, of which four were meta-analysed (summary odds ratio [OR] 0.95, 95 % confidence intervals [CI] 0.80–1.13). Two studies assessed self-reported shaking (one cluster-RCT, OR 0.11, 95 % CI 0.02–0.53; one cohort study, OR 0.36, 95 % CI 0.20–0.64, not pooled). Meta-analyses of secondary outcomes demonstrated marginal improvements in parental response to inconsolable crying (summary mean difference 1.58, 95 % CI 0.11–3.06, on a 100-point scale) and weak evidence that interventions increased walking away from crying infants (summary incidence rate ratio 1.52, 95 % CI 0.94–2.45). No intervention effects were found in meta-analyses of parental mental wellbeing or other responses to crying.InterpretationLow certainty evidence suggests that educational programmes for AHT prevention are not effective in preventing AHT. There is low to moderate certainty evidence that educational interventions have no effect or only marginally improve some parental responses to infant crying