How do network meta-analyses address intransitivity when assessing certainty of evidence: a systematic survey.

Objectives: To describe how systematic reviews with network meta-analyses (NMAs) that used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) NMA approach addressed intransitivity when assessing certainty of evidence.

Design: Systematic survey.

Data Sources: Medline, Embase and Cochrane Database of Systematic Reviews from September 2014 to October 2022.

Ketamine sedation in the intensive care unit: a survey of Canadian intensivists.

Purpose: We sought to understand the beliefs and practices of Canadian intensivists regarding their use of ketamine as a sedative in critically ill patients and to gauge their interest in a randomized controlled trial (RCT) examining its use in the intensive care unit (ICU).

Methods: We designed and validated an electronic self-administered survey examining the use of ketamine as a sedative infusion for ICU patients. We surveyed 400 physician members of the Canadian Critical Care Society (CCCS) via email between February and April 2022 and sent three reminders at two-week intervals.

Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials.

Background: To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19.

Methods: We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other.

Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis.

Objective: To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19).

Design: Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data.

Data Sources: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021).

How do cancer screening guidelines trade off benefits versus harms and burdens of screening? A systematic survey.

Objectives: Cancer screening guidelines differ in their recommendations for or against screening. To be able to provide explicit recommendations, guidelines need to specify thresholds for the magnitude of benefits of screening, given its harms and burdens. We evaluated how current cancer screening guidelines address the relative importance of benefits versus harms and burdens of screening.

Establishing thresholds for important benefits considering the harms of screening interventions.

Context And Objective: Standards for clinical practice guidelines require explicit statements regarding how values and preferences influence recommendations. However, no cancer screening guideline has addressed the key question of what magnitude of benefit people require to undergo screening, given its harms and burdens. This article describes the development of a new method for guideline developers to address this key question in the absence of high-quality evidence from published literature.

A living WHO guideline on drugs for covid-19.

Updates: This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline.

Clinical Question: What is the role of drugs in the treatment of patients with covid-19?

Context: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway.

Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: an updated systematic review and network meta-analysis of randomized trials.

Purpose: Motivated by a new randomized trial (the PEPTIC trial) that raised the issue of an increase in mortality with proton pump inhibitors (PPIs) relative to histamine-2 receptor antagonists (H2RAs), we updated our prior systematic review and network meta-analysis (NMA) addressing the impact of pharmacological gastrointestinal bleeding prophylaxis in critically ill patients.

Methods: We searched for randomized controlled trials that examined the efficacy and safety of gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. We performed Bayesian random-effects NMA and conducted analyses using all PEPTIC data as well as a restricted analysis using only PEPTIC data from high compliance centers.

Drug treatments for covid-19: living systematic review and network meta-analysis.

Objective: To compare the effects of treatments for coronavirus disease 2019 (covid-19).

Design: Living systematic review and network meta-analysis.

Data Sources: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021.

Individual opioids, and long- versus short-acting opioids, for chronic noncancer pain: Protocol for a network meta-analysis of randomized controlled trials.

Background: Opioids are frequently prescribed for the management of patients with chronic non-cancer pain (CNCP). Previous meta-analyses of efficacy and harms have combined treatment effects across all opioids; however, specific opioids, pharmacokinetic properties (ie, long acting vs short acting), or the type of formulation (ie, immediate vs extended release) may be a source of heterogeneity for pooled effects.

Methods: We will conduct a network meta-analysis (NMA) of randomized controlled trials evaluating opioids for CNCP.

Development of the summary of findings table for network meta-analysis.

Objectives: The aim of the study was to develop a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) summary of findings (SoF) table format that displays the critical information from a network meta-analysis (NMA).

Study Design And Setting: We applied a user experience model for data analysis based on four rounds of semistructured interviews.

Results: We interviewed 32 stakeholders who conduct or use MA.

Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis.

Objective: To assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute minor ischaemic stroke or transient ischaemic attack (TIA).

Design: Systematic review and meta-analysis of randomised, placebo controlled trials.

Data Sources: Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, ClinicalTrials.

Antiretroviral resistance testing in HIV-positive people.

Background: Resistance to antiretroviral therapy (ART) among people living with human immunodeficiency virus (HIV) compromises treatment effectiveness, often leading to virological failure and mortality. Antiretroviral drug resistance tests may be used at the time of initiation of therapy, or when treatment failure occurs, to inform the choice of ART regimen. Resistance tests (genotypic or phenotypic) are widely used in high-income countries, but not in resource-limited settings.

α-Blockers for uncomplicated ureteric stones: a clinical practice guideline.

Objective: To develop an evidence-based recommendation concerning the use of α-blockers for uncomplicated ureteric stones based on an up-to-date Cochrane review, as the role of medical expulsive therapy for uncomplicated ureteric stones remains controversial in the light of new contradictory trial evidence.

Methods: We applied the Rapid Recommendations approach to guideline development, which represents an innovative approach by an international collaborative network of clinicians, researchers, methodologists and patient representatives seeking to rapidly respond to new, potentially practice-changing evidence with recommendations developed according to standards for trustworthy guidelines.

Results: The panel suggests the use of α-blockers in addition to standard care over standard care alone in patients with uncomplicated ureteric stones (weak recommendation based on low-quality evidence).

Applying GRADE to a network meta-analysis of antidepressants led to more conservative conclusions.

Objective: To explore the impact of applying the Grading of Recommendations and Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence in a published network meta-analysis (NMA) of antidepressant therapies.

Study Design And Settings: We applied the GRADE approach to rate the certainty of the evidence for two outcomes, efficacy and acceptability, in each of the 66 paired comparisons within a previously published NMA assessing the relative efficacy and acceptability of 12 new-generation antidepressants.

Results: For the outcome of efficacy, of the 25 comparisons in which the 95% CrI of OR excluded 1, 18 had certainty of evidence rated high or moderate.

Early vasopressor use following traumatic injury: a systematic review.

Objectives: Current guidelines suggest limiting the use of vasopressors following traumatic injury; however, wide variations in practice exist. Although excessive vasoconstriction may be harmful, these agents may help reduce administration of potentially harmful resuscitation fluids. This systematic review aims to compare early vasopressor use to standard resuscitation in adults with trauma-induced shock.

Evidence-based guidelines for supportive care of patients with Ebola virus disease.

The 2013-16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive care to patients admitted to Ebola treatment units.

Advances in the GRADE approach to rate the certainty in estimates from a network meta-analysis.

This article describes conceptual advances of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group guidance to evaluate the certainty of evidence (confidence in evidence, quality of evidence) from network meta-analysis (NMA). Application of the original GRADE guidance, published in 2014, in a number of NMAs has resulted in advances that strengthen its conceptual basis and make the process more efficient. This guidance will be useful for systematic review authors who aim to assess the certainty of all pairwise comparisons from an NMA and who are familiar with the basic concepts of NMA and the traditional GRADE approach for pairwise meta-analysis.

Values and preferences of women living with HIV who are pregnant, postpartum or considering pregnancy on choice of antiretroviral therapy during pregnancy.

Objective: To investigate women's values and preferences regarding antiretroviral therapy (ART) during pregnancy to inform a Rapid Recommendation.

Setting: Primary studies reporting patient-reported outcomes relevant to decision-making regarding ART in any clinical and geographical setting.

Participants: Women living with HIV who are pregnant, postpartum or considering pregnancy.

Antiretroviral therapy for pregnant women living with HIV or hepatitis B: a systematic review and meta-analysis.

Objective: To assess the impact of various antiretroviral/antiviral regimens in pregnant women living with HIV or hepatitis B virus (HBV).

Design: We performed random effects meta-analysis for HIV-related outcomes and network meta-analysis for HBV outcomes, and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess quality separately for each outcome.

Data Sources: Embase and Medline to February 2017.

Structural valve deterioration after transcatheter aortic valve implantation.

Background: Transcatheter aortic valve implantation (TAVI), widely used to treat high-risk patients with severe symptomatic aortic stenosis, has recently been extended to younger patients at lower operative risk in whom long-term durability of TAVI devices is an important concern. Therefore, we conducted a systematic review and meta-analysis of observational studies addressing the frequency of structural valve deterioration (SVD) after TAVI.

Methods: We searched Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to September 2016.

Corticosteroids in sepsis: an updated systematic review and meta-analysis (protocol).

Introduction: Sepsis is associated with a dysregulated host response to infection and impaired endogenous corticosteroid metabolism. As such, therapeutic use of exogenous corticosteroids is a promising adjunctive intervention. Despite a large number of trials examining this research question, uncertainty persists regarding the effect of corticosteroids on survival in sepsis.

A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension.

Purpose: Clinicians must balance the risks from hypotension with the potential adverse effects of vasopressors. Experts have recommended a mean arterial pressure (MAP) target of at least 65 mmHg, and higher in older patients and in patients with chronic hypertension or atherosclerosis. We conducted a systematic review of randomized-controlled trials comparing higher vs lower blood pressure targets for vasopressor therapy administered to hypotensive critically ill patients.