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Methods: Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models. Results: The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine (P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10–12.33 (P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28–10.99 (P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29–2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00–3.20; P = 0.049). Conclusion: This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first‐line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain.

Objectives To determine whether recently published and ongoing systematic reviews of therapeutic interventions assess patient-important outcomes. Study Design and Setting For this methodological review, we searched MEDLINE via PubMed for recently published systematic reviews and online registry of systematic reviews (PROSPERO) for ongoing systematic reviews. We selected systematic reviews with meta-analyses of randomized controlled trials. We extracted all outcomes defined in the methods section and categorized them. Mortality, other clinical events, pain, quality of life, function, and therapeutic decisions were considered patient-important outcomes. Results We included 420 systematic reviews: 90 Cochrane reviews, 200 other published reviews, and 130 registered ongoing reviews. Primary outcomes were defined in 85 Cochrane reviews (95%), 98 (49%) other published reviews and all ongoing reviews. At least one patient-important outcome was defined as a primary outcome in 81/85 Cochrane reviews (95%), 78/98 other published reviews (80%), and 117/130 ongoing reviews (90%). Considering all outcomes assessed, at least one patient-important outcome was evaluated in 90/90 Cochrane reviews (100%), 189/200 other published reviews (95%), and 121/130 ongoing reviews (93%). Conclusion Most recent systematic reviews aim to assess patient-important outcomes, which contrasts with RCTs. These results suggest some important gaps between primary and secondary research.

The objective of the study was to explore contextual factors associated with high or low risk-of-bias judgment in case of incomplete or unclear information in study reports.Research-on-research study, using matched case-control design, with a sample of 304 randomized controlled trials (RCTs) included in two Cochrane reviews for which there was disagreement on the risk-of-bias judgment related to incomplete or unclear information in the study report. A case was defined as an RCT judged at high or low risk of bias; a control was the same RCT judged at unclear risk. We used a conditional logistic regression model for analysis.Review authors being also authors of the RCT were more likely to assess an item at low risk of bias than unclear (OR: 11.71; 95% CI: 1.39-98.76). Earlier trials in a review were more often assigned a low risk (OR: 0.37; [0.15-0.96]). Review groups and authors that had completed a lower number of reviews slightly more often assigned a low risk, whereas others reported "unclear" (OR: 0.97, [95% CI: 0.95-0.99] for groups) and 0.97 (95% CI: 0.95-0.998) for authors).Risk-of-bias assessment of RCTs in case of incomplete or unclear information may be affected by contextual factors.

IntroductionImproving the appropriateness of prescriptions of oral antithrombotic (AT) drugs, especially AT combinations, is crucial because these drugs are implicated in bleeding events. We developed a prescription support-tool synthesising guidelines on chronic management of oral AT combinations. Our main objective is to assess the impact of this tool on improving the prescription of oral ATs to comply with guidelines.Methods and analysisA randomised controlled trial will be conducted among French general practitioners and cardiologists involved in outpatient settings. Physicians will be invited to participate to an online survey by email via physician associations, social networks or word of mouth. They will be randomised to two arms: the experimental arm (access to the prescription support-tool) or the control arm (no prescription support-tool). Then, all participants will be presented three different clinical vignettes illustrating outpatient clinical situations and will be asked to propose prescriptions for each vignette (number of ATs, type, dosage and duration). A computer-generated randomisation scheme implemented in the online survey will be used to allocate physicians to the experimental or control arm and then stratified by medical specialty. The primary outcome will be fully appropriate prescription of oral ATs ie, that comply with the guidelines in terms of number of drugs, drug class, dosage and duration. To demonstrate a 5% increase in this proportion, we will need to include a minimum of 230 physicians per arm. A logistic mixed model with a clinical vignette-effect and a physician-effect nested in the arm of the study will be used.Ethics and disseminationTheInstitutional Review Boardof Inserm (IRB00003888) approved our research project (no. 18–492). If the prescription support-tool improves the prescription of oral ATs, we will create an interactive web tool and will assess its impact in terms of clinical outcomes in real-life.Trial registration numberNCT03630874; Pre-results.

International audience; Glyphosate is found in a large array of non-selective herbicides such as Roundup® (Monsanto, Creve Coeur, MO, USA) and is by far the most widely used herbicide. Recent work in rodent models suggests that glyphosate-based herbicides during development can affect neuronal communication and result in altered behaviours, albeit through undefined mechanisms of action. To our knowledge, no study has investigated the effects glyphosate or its formulation in herbicide on maternal behaviour and physiology. In the present study, relatively low doses of glyphosate (5 mg kg-1 d-1 ), Roundup® (5 mg kg-1 d-1 glyphosate equivalent), or vehicle were administered by ingestion to Sprague-Dawley rats from gestational day (GD) 10 to postpartum day (PD)22. The treatments significantly altered licking behaviour toward pups between PD2 and PD6. We also show in the dams at PD22 that Roundup exposure affected the maturation of doublecortin-immunoreactive new neurones in the dorsal dentate gyrus of the hippocampus of the mother. In addition, the expression of synaptophysin was up-regulated by glyphosate in the dorsal and ventral dentate gyrus and CA3 regions of the hippocampus, and down-regulated in the cingulate gyrus. Although a direct effect of glyphosate alone or its formulation on the central nervous system is currently not clear, we show that gut microbiota is significantly altered by the exposure to the pesticides, with significant alteration of the phyla Bacteroidetes and Firmicutes. This is the first study to provide evidence that glyphosate alone or in formulation (Roundup) differentially affects maternal behaviour and modulates neuroplasticity and gut microbiota in the mother.

ObjectivesAssess the frequency and reasons for disagreements in risk of bias assessments for randomised controlled trials (RCTs) included in more than one Cochrane review. DesignResearch on research study, using cross-sectional design. Data sources2796 Cochrane reviews published between March 2011 and September 2014. Data selectionRCTs included in more than one review. Data extractionRisk of bias assessment and support for judgement for five key risk of bias items. Data synthesisFor each item, we compared risk of bias assessment made in each review and calculated proportion of agreement. Two reviewers independently analysed 50% of all disagreements by comparing support for each judgement with information from study report to evaluate whether disagreements were related to a difference in information (eg, contact the study author) or a difference in interpretation (same support for judgement but different interpretation). They also identified main reasons for different interpretation. Results1604 RCTs were included in more than one review. Proportion of agreement ranged from 57% (770/1348 trials) for incomplete outcome data to 81% for random sequence generation (1193/1466). Most common source of disagreement was difference in interpretation of the same information, ranging from 65% (88/136) for random sequence generation to 90% (56/62) for blinding of participants and personnel. Access to different information explained 32/136 (24%) disagreements for random sequence generation and 38/205 (19%) for allocation concealment. Disagreements related to difference in interpretation were frequently related to incomplete or unclear reporting in the study report (83% of disagreements related to different interpretation for random sequence generation). ConclusionsRisk of bias judgements of RCTs included in more than one Cochrane review differed substantially. Most disagreements were related to a difference in interpretation of an incomplete or unclear description in the study report. A clearer guidance on common causes of incomplete information may improve agreement.

Background Cluster randomized trials (CRTs) and individually randomized trials (IRTs) are often pooled together in meta-analyses (MAs) of randomized trials. However, the potential systematic differences in intervention effect estimates between these two trial types has never been investigated. Therefore, we conducted a meta-epidemiological study comparing intervention effect estimates between CRTs and IRTs. Methods All Cochrane MAs including at least one CRT and one IRT, published between 1 January 2010 and 31 December 2014, were included. For each MA, we estimated a ratio of odds ratios (ROR) for binary outcomes or a difference of standardized differences (DSMD) for continuous outcomes, where less than 1 (or 0, respectively) indicated a greater intervention effect estimate with CRTs. Results Among 1301 screened reviews, we selected 121 MAs, of which 76 had a binary outcome and 45 had a continuous outcome. For binary outcomes, intervention effect estimates did not differ between CRTs and IRTs [ROR 1.00, 95% confidence interval (0.93 to 1.08)]. Subgroup and adjusted analyses led to consistent results. For continuous outcomes, the DSMD was 0.13 (0.06 to 0.19). It was lower for MAs with a pharmacological intervention [-0.03, (-0.12 to 0.07)], an objective outcome [0.05, (-0.08 to 0.17)] or after adjusting for trial size [0.06, (-0.01 to 0.15)]. Conclusion For binary outcomes, CRTs and IRTs can safely be pooled in MAs because of an absence of systematic differences between effect estimates. For continuous outcomes, the results were less clear although accounting for trial sample sizes led to a non-significant difference. More research is needed for continuous outcomes and, meanwhile, MAs should be completed with subgroup analyses (CRTs vs IRTs).

This study followed 173 newborn infants in the PREmedication Trial for Tracheal Intubation of the NEOnate multicenter, double-blind, randomized controlled trial of atropine-propofol vs atropine-atracurium-sufentanil for premedication before nonemergency intubation. At 2 years of corrected age, there was no significant difference between the groups in death or risk of neurodevelopmental delay assessed with the Ages and Stages Questionnaire. Trial registration Clinicaltrials.gov : NCT01490580 .

Introduction Le syndrome de Gleich ou angioedeme avec hypereosinophilie est une entite rare associant des crises recurrentes d’angioedeme avec hypereosinophilie concomitante et elevation frequente d’immunoglobulines M seriques polyclonales. Patients et methodes Nous avons conduit une etude retrospective nationale multicentrique afin d’evaluer le spectre clinique et la prise en charge therapeutique des angiœdemes avec hypereosinophilie. Resultats Trente patients ont ete inclus avec un âge median au diagnostic de 41 ans [5–84]. La duree mediane de chaque crise d’angiœdeme etait de 5,5 jours [1–90] avec atteinte principale du visage et des membres superieurs. Le taux seriques d’immunoglobuline M etait eleve pour 20 patients (67 %). Un phenotype lymphocytaire T aberrant etait detecte chez 12 patients (40 %) avec mise en evidence d’un rearrangement clonal du TCR γ chez 5 de ces patients (17 %). Le suivi median etait de 53 mois [31-99]. Tous les patients ont recu une corticotherapie initialement efficace, mais 15 patients ont rechute apres cette premiere ligne (50 %) justifiant une deuxieme ou troisieme ligne de traitement par interferon-α (n = 8,27 %), mepolizumab (n = 2,7 %), ciclosporine A (n = 5,17 %), methotrexate (n = 4,13 %) ou hydroxycarbamide (n = 2,7 %). La presence d’un phenotype lymphocytaire aberrant etait le seul facteur associe aux rechutes (hazard ratio 4,15 [IC 95 % 1,18–14,66] ;p = 0,02). Lors du dernier suivi, 3 patients (10 %) etaient sevres de tout traitement et 11 patients (37 %) etaient en remission clinique et biologique sous moins de 10 mg d’equivalent prednisone par jour. Conclusion Le syndrome de Gleich ou angiœdeme avec hypereosinophilie est une entite heterogene au sein des syndromes hypereosinophiliques. Bien que les patients presentent une bonne reponse a la corticotherapie, les patients porteurs d’un phenotype lymphocytaire T aberrant ont un risque de rechute augmente.