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Background: Superiority of perineural over intravenous dexamethasone at extending nerve block analgesia has been suggested but without considering the dose-response relationships for each route of administration., Methods: Randomised control studies that evaluated intravenous or perineural dexamethasone as an adjuvant to unilateral peripheral nerve blocks in adults were searched up to October 2023 in MEDLINE, Central, Google Scholar, and reference lists of previous systematic reviews. The Cochrane Risk-of-Bias tool was used. A maximum effect (E max ) model-based network meta-analysis was undertaken to evaluate the dose-response relationships of dexamethasone., Results: A total of 118 studies were selected (9284 patients; 35 with intravenous dexamethasone; 106 with perineural dexamethasone; dose range 1-16 mg). Studies with unclear or high risk of bias overestimated the effect of dexamethasone. Bias-corrected estimates indicated a maximum fold increase in analgesia duration of 1.7 (95% credible interval (CrI) 1.4-1.9) with dexamethasone, with no difference between perineural and intravenous routes. Trial simulations indicated that 4 mg of perineural dexamethasone increased the mean duration of analgesia for long-acting local anaesthetics from 11.1 h (95% CrI 9.4-13.1) to 16.5 h (95% CrI 14.0-19.3) and halved the rate of postoperative nausea and vomiting. A similar magnitude of effect was observed with 8 mg of intravenous dexamethasone., Conclusions: Used as an adjuvant for peripheral nerve block, intravenous dexamethasone can be as effective as perineural dexamethasone in prolonging analgesic duration, but is less potent, hence requiring higher doses. The evidence is limited because of the observational nature of the dose-response relationships and the quality of the included studies., Systematic Review Protocol: PROSPERO CRD42020141689., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: To perform an overview of the overlap of systematic reviews (SRs) assessing direct oral anticoagulants and characterize these reviews in terms of bias and methodological quality (PROSPERO: CRD42022316273)., Study Design and Setting: A PubMed-indexed search was performed from inception to January 31, 2022 to identify SRs evaluating direct oral anticoagulants in patients treated for an acute venous thromboembolism. The risk of bias of these SRs was assessed according to the Risk Of Bias In Systematic reviews tool. Redundancy was defined as overlap in terms of the type of population considered, the interventions compared, and the studies included., Results: A total of 144 SRs were evaluated, of which 26 (18.1%) were classified as original, 87 (60.4%) as conceptual replications, and 31 (21.5%) as excessive replications. The risk of bias was high in 19 (73.1%) of the original SRs, 65 (74.7%) of the conceptual replications, and 21 (67.7%) of the excessive replications. Compared to the original SRs, the overall methodological quality was not improved in either conceptual or excessive replications., Conclusion: A large number of SRs was classified as replications; a fifth constituted excessive replications. The replications showed no improvement in overall methodological quality compared to the original SRs., Competing Interests: Declaration of competing interest Céline Chapelle, Edouard Ollier, Paul Bonjean, Clara Locher, and Paul Jacques Zufferey: none. Michel Cucherat has received personal fees from Bayer and BMS for consulting. Silvy Laporte has received personal fees from Bayer for consulting, personal fees continuing medical education lectures from Pfizer, and personal fees for continuing medical education lectures from Eli Lilly., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Few studies compare the efficacy of the key bariatric procedures in type 2 diabetes management over the long term. None offer a reliable comparison of their respective efficacy loss over time., Objectives: To analyze and compare the time evolution of the antidiabetic effects of the key bariatric procedures., Setting: Obesity surgery departments in America, Europe, and Asia., Methods: All the randomized clinical trials assessing the efficacy of bariatric surgery in type 2 diabetes management with 1-5 years of follow-up were reviewed. A network meta-analysis with meta-regression was performed to compare the effectiveness of each technique and its respective efficacy loss temporal dynamics., Results: Thirty-one trials involving 1906 patients were included. In comparison to Roux-en-Y gastric bypass, the 5-year complete or partial diabetes remission rates were inferior with medical treatment (odds ratio [OR] = .05; 95% credible interval [CrI]: .02-.13) and gastric banding (OR = .38; 95% CrI: .16-.87), equivalent with sleeve gastrectomy (OR = 1.08; 95% CrI: .59-1.97), and superior with 1 anastomosis gastric bypass (OR = 3.00; 95% CrI: 1.12-8.33) and biliopancreatic diversion and its affiliated techniques (OR = 3.71; 95% CrI: 1.16-12.55). However, remission rates and glycemic control progressively decreased whatever the treatment option evaluated. Moreover, this loss of efficacy followed a statistically comparable temporal dynamic to those of Roux-en-Y gastric bypass regardless of the therapeutic strategy implemented., Conclusions: No therapeutic modality offered stable antidiabetic effects. The gap observed between the techniques after a 5-year follow up concerning remission rates and glycemic control could depend essentially on the magnitude of the effects initially obtained. However, these results need to be confirmed over longer follow-up periods., (Copyright © 2022 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Meta-analyses are widely used to strengthen available evidence and obtain more precise estimates of treatment effect than any individual trial. Paradoxically, multiplication of meta-analyses on the same topic can lead to confusion as practitioners no longer benefit from a rapid and synthetic response. This phenomenon may appear disproportionate when the number of published meta-analyses exceeds the number of original studies., Objectives: To describe an example of redundant meta-analyses published in the same area with the same randomized clinical trials (RCTs)., Methods: A systematic review was performed to identify all published meta-analyses of original RCTs that compared direct oral anticoagulants with low molecular weight heparins in cancer patients with venous thromboembolism (VTE). Forest plots were used to represent the meta-analyses results for efficacy (VTE recurrence) and safety (major bleeding) endpoints. An authors' network was constructed to explore the links between the authors of the published meta-analyses., Results: In the past 3 years, four original RCTs were the subject of 20 published meta-analyses by 142 authors: five, four, and 11 meta-analyses pooled the data of two, three, and four RCTs, respectively. The results of meta-analyses were similar regarding the risks of VTE recurrence and major bleeding. The 11 meta-analyses of four RCTs were published within 6 months of the publication of the last RCT., Conclusions: The epidemic proportions of such redundant literature and authorship could be moderated by developing "living" meta-analyses and encouraging authors of new RCTs to update the corresponding meta-analysis in the same paper as their original research., (© 2021 International Society on Thrombosis and Haemostasis.)

Background and Objectives: Randomized controlled trials (RCTs) are criticized for including patients who are overselected. Health authorities consequently encourage "real-world" postmarketing cohort studies. Our objective was to determine the differences between RCTs and observational studies as regards their populations and efficacy/safety results., Methods: A systematic review was conducted to identify RCTs and observational studies including patients with venous thromboembolism receiving direct oral anticoagulants or conventional treatment. Ratios of hazard ratio (RHR) comparing epidemiological studies (prospective and retrospective cohort studies and studies using living databases) with RCTs were computed., Results: Six RCTs (27,121 patients) and twenty observational studies (248,971 patients) were identified and analyzed. Prospective cohort studies seemed to recruit patients who were no less selected than those of RCTs whereas other types of observational studies may reflect the population treated in real life. Among observational studies, prospective cohort studies yielded the most favorable estimates of treatment effect compared with RCTs. These studies were associated with a nonsignificant 33% increase in efficacy estimate (RHR 0.67, [95% CI, 0.39-1.18]) but no effect on safety estimate. Studies using living databases were associated with nonsignificant trends toward a greater effect on efficacy (RHR 0.82, [0.66-1.01]) and a smaller effect on safety (RHR 1.33, [0.96-1.84])., Discussion: Overall, in this clinical setting, an exaggeration of the treatment efficacy estimate was seen with observational studies compared with RCTs., Conclusions: As the presence of residual confounding cannot be excluded, these results should be interpreted cautiously., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: 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., Objective: We systematically review and analyze the comparative literature between surgical and conservative treatments of odontoid fractures., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: An unexpected promising effect of low molecular weight heparins (LMWHs) on survival in patients with cancer was observed in early trials in post hoc subgroup analyses but not found in more recent trials. To highlight a possible regression over time toward the lack of the antitumoral effect of LMWHs, we performed a cumulative meta-analysis of survival data from randomized controlled trials (RCTs)., Study Design and Setting: Medical databases were searched to identify RCTs comparing, in patients with cancer, LMWHs with placebo or no treatment in patients free of venous thromboembolism (VTE), or to vitamin K antagonists in patients who experienced an acute VTE in overall survival. The cumulative hazard ratio (HR) was estimated after each study inclusion in chronological order., Results: Twenty-three studies (12,970 patients) were included. The cumulative meta-analysis of the earlier trials showed a significant improvement in overall survival with LMWHs. This apparent benefit then gradually regressed over time toward an absence of the effect of LMWHs on survival (HR: 0.98 [95% confidence interval, 0.93; 1.03])., Conclusion: Despite supportive experimental data and early clinical findings, the promising antitumoral effect of LMWHs in patients with cancer gradually vanished over time toward a lack of impact on overall survival. This result suggests 'p-hacking' and selective reporting of the positive results from post hoc subgroup analyses in the early studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Detection of severe renal impairment in patients with venous thromboembolism (VTE) is mandatory both for selecting anticoagulant therapy and for evaluating major bleeding risk, increased by severe renal impairment., Objectives: To determine whether the Cockcroft and Gault (CG) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas identify severe renal impairment in the same VTE patients presenting the same risk of major bleeding., Patients/methods: We compared clinical characteristics and outcomes during the first 3 months of anticoagulation between VTE patients in the RIETE registry with severe renal impairment according to the CG and/or CKD-EPI formula (estimated glomerular filtration rate <30 mL/min and <30 mL/min/1.73 m 2 , respectively). The primary outcome was major bleeding., Results: Up to October 2017, 41 796 patients were included in RIETE. Among the 4676 patients with severe renal impairment according to at least one of the formulas, this was not confirmed by the other formula in 1904 (40.7%). Major bleeding risk was increased in every patient subgroup with severe renal impairment vs patients without this condition (CG or CKD-EPI < 30: odds ratio [OR] = 2.26, 95% confidence interval [CI 2.01-2.53], only CG < 30: OR = 1.72, 95% CI [1.37-2.13], only CKD-EPI < 30: OR = 2.34, 95% CI [1.77-3.05], CG+CKD-EPI < 30: OR = 2.47, 95% CI [2.16-2.83], all vs CG+CKD-EPI > 30)., Conclusion: The CG and CKD-EPI formulas identify different subgroups of patients with severe renal impairment, leading to discordant results in 40.7% of these patients. Irrespective of the formula used for their identification, patients with severe renal impairment have a higher risk of major bleeding under anticoagulant therapy., (© 2020 International Society on Thrombosis and Haemostasis.)

The treatment of acute venous thromboembolism (VTE) is being completely modified with the development of direct oral anticoagulants (DOACs). Rivaroxaban, apixaban and edoxaban directly inhibit factor Xa, whereas dabigatran inhibits factor IIa. All these drugs are proposed orally, and share pharmacological similarities: fixed doses without any therapeutic drug monitoring, key role of the transporter proteins P-glycoprotein for all of them and metabolism mediated by CYP3A4 for the anti-Xa, short half-life with variable rate of renal elimination. More than 25 000 patients with acute VTE were included in phase-III studies. Rivaroxaban and apixaban challenged all the conventional therapy (parenteral heparins followed by anti-vitamin K antagonists) whereas edoxaban and dabigatran challenged only anti-vitamin K antagonists. All the DOACs met the non-inferiority efficacy endpoint (recurrent VTE during treatment), whereas the large non-inferiority margin was debated for dabigatran. However, they were associated with better safety and a decreased risk of major bleeding. According to indirect comparisons, there were no statistically significant differences between DOACs in terms of efficacy but some differences are not excluded in term of safety. Although DOACs allow for simplification of treatment in the majority of patients with acute VTE, their risk/benefit ratio is questioned in elderly patients, patients with mild-to-severe renal impairment, and in some clinical subgroups such as cancer or chronic thromboembolic pulmonary hypertension. Validated reversal strategies (potentially based on laboratory monitoring) are expected for patients with major bleeding, overdose or with a need for surgery., (Copyright © 2016 Elsevier Ltd. All rights reserved.)