Defining clinically important perioperative blood loss and transfusion for the Standardised Endpoints for Perioperative Medicine (StEP) collaborative: a protocol for a scoping review

INTRODUCTION: 'Standardised Endpoints for Perioperative Medicine' (StEP) is an international collaboration undertaking development of consensus-based consistent definitions for endpoints in perioperative clinical trials. Inconsistency in endpoint definitions can make interpretation of trial results more difficult, especially if conflicting evidence is present. Furthermore, this inconsistency impedes evidence synthesis and meta-analyses. The goals of StEP are to harmonise definitions for clinically meaningful endpoints and specify standards for endpoint reporting in clinical trials. To help inform this endeavour, we aim to conduct a scoping review to systematically characterise the definitions of clinically important endpoints in the existing published literature on perioperative blood loss and transfusion. METHODS AND ANALYSIS: The scoping review will be conducted using the widely adopted framework developed by Arksey and O'Malley, with modifications from Levac. We refined our methods with guidance from research librarians as well as researchers and clinicians with content expertise. The electronic literature search will involve several databases including Medline, PubMed-not-Medline and Embase. Our review has three objectives, namely to (1) identify definitions of significant blood loss and transfusion used in previously published large perioperative randomised trials; (2) identify previously developed consensus-based definitions for significant blood loss and transfusion in perioperative medicine and related fields; and (3) describe the association between different magnitudes of blood loss and transfusion with postoperative outcomes. The multistage review process for each question will involve two reviewers screening abstracts, reading full-text articles and performing data extraction. The abstracted data will be organised and subsequently analysed in an iterative process. ETHICS AND DISSEMINATION: This scoping review of the previously published literature does not require research ethics approval. The results will be used to inform a consensus-based process to develop definitions of clinically important perioperative blood loss and transfusion. The results of the scoping review will be published in a peer-reviewed scientific journal

A living WHO guideline on drugs for covid-19

CITATION: Agarwal, A. et al. 2022. A living WHO guideline on drugs for covid-19. British Medical Journal, 370. doi:10.1136/bmj.m3379The original publication is available at https://jcp.bmj.com/This living guideline by Arnav Agarwal and colleagues (BMJ 2020;370:m3379, doi:10.1136/bmj.m3379) was last updated on 22 April 2022, but the infographic contained two dosing errors: the dose of ritonavir with renal failure should have read 100 mg, not 50 mg; and the suggested regimen for remdesivir should have been 3 days, not 5-10 days. The infographic has now been corrected.Publishers versio

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications

BackgroundThere is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research

Antibiotic therapy for skin and soft tissue infections: a protocol for a systematic review and network meta-analysis

Abstract Background Skin and soft tissue infections (SSTIs) in hospital and community settings impose a substantial socio-economic burden. Therapeutic uncertainty due to the availability of a wide range of antibiotics and the need for empirical treatment decisions complicate SSTI clinical management. Completion of numerous pairwise meta-analyses to account for this variability in antibiotics is impractical, and many head-to-head comparisons of potential interest are likely not available. In comparing multiple antibiotics simultaneously, this network meta-analysis aims to identify the antibiotic(s) with the greatest value in the treatment of SSTIs, in terms of patient-important outcomes such as efficacy and safety. Methods We will conduct a systematic review to identify randomized controlled trials of persons with suspected or confirmed SSTI assigned to orally or parenterally administered antibiotic therapy that report results on at least one outcome of interest. We will search MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL), along with trial registries. Our primary outcome of interest is clinical success at the test-of-cure visit. Secondary outcomes may include (1) early clinical success (2–3 days after the therapy starts), (2) mortality, (3) adverse events, (4) treatment duration, and (5) length of hospital stay. Independent reviewers will complete screening of titles, abstracts, and full texts, data extraction, risk of bias assessment (using the Cochrane Risk of Bias tool), and evaluation of the certainty of evidence (using the GRADE approach) in duplicate. We will complete pairwise and network meta-analyses within the Bayesian framework when possible using a random effects model. We will stratify SSTIs by severity into uncomplicated and complicated SSTIs when possible. Subgroup analyses by age, infection type, comorbidity, and suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA)-associated infection are planned. Discussion This study has several strengths compared to previous reviews: inclusion of a wider range of infection types, antibiotics, and outcomes; a comprehensive search strategy; a priori subgroup analyses; application of GRADE; and improved interpretability of findings through visual presentation of results. We hope our findings will inform future research, health care professionals, and policy makers resulting in improved evidence-based clinical management of SSTIs. Systematic review registration PROSPERO CRD4201808560

Prognostic factors for streptococcal toxic shock syndrome: systematic review and meta-analysis

Objectives To quantify the prognostic effects of demographic and modifiable factors in streptococcal toxic shock syndrome (STSS).Design Systematic review and meta-analysis.Data sources MEDLINE, EMBASE and CINAHL from inception to 19 September 2022, along with citations of included studies.Eligibility criteria Pairs of reviewers independently screened potentially eligible studies of patients with Group A Streptococcus-induced STSS that quantified the association between at least one prognostic factor and outcome of interest.Data extraction and synthesis We performed random-effects meta-analysis after duplicate data extraction and risk of bias assessments. We rated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach.Results One randomised trial and 40 observational studies were eligible (n=1918 patients). We found a statistically significant association between clindamycin treatment and mortality (n=144; OR 0.14, 95% CI 0.06 to 0.37), but the certainty of evidence was low. Within clindamycin-treated STSS patients, we found a statistically significant association between intravenous Ig treatment and mortality (n=188; OR 0.34, 95% CI 0.15 to 0.75), but the certainty of evidence was also low. The odds of mortality may increase in patients ≥65 years when compared with patients 18–64 years (n=396; OR 2.37, 95% CI 1.47 to 3.84), but the certainty of evidence was low. We are uncertain whether non-steroidal anti-inflammatory drugs increase the odds of mortality (n=50; OR 4.14, 95% CI 1.13 to 15.14; very low certainty). Results failed to show a significant association between any other prognostic factor and outcome combination (very low to low certainty evidence) and no studies quantified the association between a prognostic factor and morbidity post-infection in STSS survivors.Conclusions Treatment with clindamycin and within clindamycin-treated patients, IVIG, was each significantly associated with mortality, but the certainty of evidence was low. Future research should focus on morbidity post-infection in STSS survivors.PROSPERO registration number CRD42020166961