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The number of meta‐analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy‐to‐use, and specialised statistical software. Even when meta‐analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta‐analysis provides an example of the variation of effect 'naturally' observed between multiple research projects. Reproducibility of results has mostly been reported using graphical descriptive representations. A quantitative analysis of such results would enable (i) breakdown of the total observed variability with quantification of the variability generated by the replication process and (ii) identification of which variables account for this variability, such as methodological quality or the statistical analysis procedures used. These variables might explain systematic mean differences between results and dispersion of the results. To quantitatively characterise the reproducibility of meta‐analysis results, a bivariate linear mixed‐effects model was developed to simulate both mean results and their corresponding uncertainty. Results were assigned to several replication groups, those assessing the same studies, outcomes, treatment indication and comparisons classified in the same replication group. A nested random effect structure was used to break down the total variability within each replication group and between these groups to enable calculation of an intragroup correlation coefficient and quantification of reproducibility. Determinants of variability were investigated by modelling both mean and variance parameters using covariates. The proposed model was applied to the example of meta‐analyses evaluating direct oral anticoagulants in the acute treatment of venous thromboembolism. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) has a poor prognosis despite a multi modal treatment that includes normofractionated radiotherapy. So, various hypofractionated alternatives to normofractionated RT have been tested to improve such prognosis. There is need of systematic review and meta-analysis to analyse the literature properly and maybe generalised the use of hypofractionation. The aim of this study was first, to perform a meta-analysis of all controlled trials testing the impact of hypofractionation on survival without age restriction and secondly, to analyse data from all non-comparative trials testing the impact of hypofractionation, radiosurgery and hypofractionated stereotactic RT in first line.Materials/methods: We searched Medline, Embase and Cochrane databases to identify all publications testing the impact of hypofractionation in glioblastoma between 1985 and March 2020. Combined hazard ratio from comparative studies was calculated for overall survival. The impact of study design, age and use of adjuvant temozolomide was explored by stratification. Meta-regressions were performed to determine the impact of prognostic factors.Results: 2283 publications were identified. Eleven comparative trials were included. No impact on overall survival was evidenced (HR: 1.07, 95%CI: 0.89-1.28) without age restriction. The analysis of non-comparative literature revealed heterogeneous outcomes with limited quality of reporting. Concurrent chemotherapy, completion of surgery, immobilization device, isodose of prescription, and prescribed dose (depending on tumour volume) were poorly described. However, results on survival are encouraging and were correlated with the percentage of resected patients and with patients age but not with median dose.Conclusions: Because few trials were randomized and because the limited quality of reporting, it is difficult to define the place of hypofactionation in glioblastoma. In first line, hypofractionation resulted in comparable survival outcome with the benefit of a shortened duration. The method used to assess hypofractionation needs to be improved. [ABSTRACT FROM AUTHOR]

The time-course response after a single injection of botulinum toxin (BoNT) for post-stroke spasticity is debated. We addressed this issue by conducting a systematic review and a pharmacodynamic model-based meta-analysis. We searched Medline, PeDro and Google Scholar databases up to March 2020, selecting randomized controlled trials of post-stroke and traumatic brain injury patients with arm or leg muscle hypertonia, comparing BoNT to placebo, or different BoNT preparations. The main outcome was change in Modified Ashworth Scale (MAS) score. A non-linear mixed effect model was used to estimate maximal toxin and placebo effects (Emax and EPlacebo), the effect disappearance half-life (T1/2off) of BoNT and the doses achieving 50 and 80% of Emax (D50 and D80). The equivalence ratios between different BoNT preparations were calculated from D50 values. Adverse events were recorded. Altogether, 2,236 unique records were screened by 2 independent reviewers: 35 eligible trials including 3011 patients (95% post-stroke) were identified. For all BoNT preparations, the BoNT Emax of -1.11 (95% credible interval -1.31; -0.29) was reached at 5 weeks; the maximal placebo effect was -0.30 (-0.37; -0.22). Both D50 and D80 differed significantly by muscle volume. At D50, the equivalence ratio was significantly higher for abobotulinumtoxinA (3.35) than onabotulinumtoxinA and lower for letibotulinumtoxinA (0.41). T1/2off was longer for abobotulinumtoxinA than for onabotulinumtoxinA and the other preparations (13.1 weeks [95% credible interval 7.7; 19.3] vs 8.6 weeks [7.1; 10.1]). Adverse events were minor, with a weak, but significant, dose–response relation for muscle weakness. This first pharmacodynamic model-based meta-analysis of individuals with stroke revealed that for all BoNT-A preparations, BoNT-A injections to treat spasticity have maximal effect at 5 weeks. The T1/2off was longer for abobotulinumtoxinA than other preparations. Differences between certain BoNT unit scales were also confirmed. [ABSTRACT FROM AUTHOR]

Odontoid fracture is a common injury especially in elderly people. Despite some recent studies arguing in favor of surgery, the best treatment is still being debated. We systematically review and analyze the comparative literature between surgical and conservative treatments of odontoid fractures. We systematically searched Medline and the Cochrane Library for studies reported from January 1990 to May 2019 in English. Comparative studies evaluating the results of surgical and conservative treatments for odontoid fractures were eligible for inclusion. Combined relative risks (RRs) for mortality at last follow-up, union or nonunion rates, and complications were calculated. Methodological quality was assessed using the Newcastle-Ottawa Scale. Influence of age and year of publication on treatment effect was explored using a meta-regression analysis. A total of 1438 articles were identified, of which 30 articles with 2463 patients were eligible for inclusion. There was a trend toward lower mortality in the surgical group (RR, 0.80; 95% confidence interval [CI], 0.63–1.02). Nonunion rates (RR, 0.41; 95% CI, 0.28–0.6) were lower in the surgical group. Union rates were higher in the surgical group (RR, 1.26; 95% CI, 1.11–1.45). No significant influence of age or year of publication on treatment effect was found. Based on this meta-analysis of nonrandomized comparative studies, surgical treatment seems not to be inferior to conservative treatments. The conclusions of this study remain limited by the low quality of the evidence available. Randomized controlled studies are required. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) causes significant morbidity and mortality in patients with traumatic injuries, despite thromboprophylaxis. To decrease both thrombotic and bleeding risks, some authors suggest adjusting the thromboprophylactic doses of low-molecular-weight heparins (LMWH), in particular according to body weight at treatment initiation or to changes in anti-factor Xa level during treatment. Our objective was to estimate in trauma patients the efficacy and safety of such adjustments, compared with the conventional strategy of fixed-dose LMWH thromboprophylaxis. A systematic review and a meta-analysis were conducted to identify and assess randomised control trials and observational studies with prospective enrolment that included trauma patients and compared adjustment of LMWH thromboprophylaxis versus no adjustment. The primary and secondary endpoints were VTE and bleeding, respectively. The Odds Ratio (OR) and 95% Confidence Interval (95% CI) were calculated using the Mantel-Haenszel method. Nine studies were included in the meta-analysis. No significant reduction in the risk of VTE was observed with adjusted doses of LMWH compared with fixed doses when considering only randomised control trials (OR 1.02 [95% CI, 0.09 to 11.6]) or all trials (OR 0.70 [95% CI, 0.34 to 1.42]). Similarly, there was no significant difference in bleeding risk (OR 1.36, 95% CI 0.59 to 3.10). This meta-analysis shows that, to date, there is no evidence to justify adjusting LMWH doses, in agreement with the recommendations of the American College of Chest Physicians. [ABSTRACT FROM AUTHOR]