Rayner, Daniel

Abstract Clinical question What are the benefits and harms of medications for adults with type 2 diabetes at varied risks of cardiovascular and kidney related complications? Context Emerging clinical trials of novel medications have demonstrated benefits on cardiovascular, kidney, and weight related outcomes in people with type 2 diabetes. Dynamically updated practice guidelines adhering to standards of trustworthiness are necessary in response to a rapidly evolving evidence base and the availability of multiple medication alternatives. This living practice guideline incorporates the latest available medications and evidence and provides recommendations stratified by risks of cardiovascular and kidney complications to inform diabetes management. Recommendations The panel issued risk-stratified recommendations regarding four prioritised medications for adults with type 2 diabetes (SGLT-2 inhibitors, GLP-1 receptor agonists, finerenone and tirzepatide): • Lower risk (three or fewer cardiovascular risk factors without established cardiovascular disease (CVD) or chronic kidney disease (CKD)): weak recommendation against SGLT-2 inhibitors or GLP-1 receptor agonists. • Moderate risk (more than three cardiovascular risk factors without established CVD or CKD; or established CVD and/or CKD at lower risk of complications): weak recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation against finerenone in adults with CKD. • Higher risk (established CVD and/or CKD at higher risk of complications, or established heart failure): strong recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation in favour of finerenone in adults with CKD. • Across risk strata: weak recommendation in favour of tirzepatide in adults with obesity. About this guideline and how it was created An international panel including two patient partners, clinicians, and methodologists produced these recommendations. The panel followed standards for trustworthy guidelines and used the GRADE approach, explicitly considering the balance of benefits, harms and burdens of treatment from an individual patient perspective. Recommendations were informed by a linked living systematic review and network meta-analysis evaluating relative benefits and harms updated to 31 July 2024; and by linked systematic reviews addressing risk prediction models and values and preferences of adults with type 2 diabetes. Candidate therapeutics are prioritised based on availability of sufficient randomised trial data, relevance to a global audience and likelihood of changing practice. This is the first version of the living guideline. The guideline is part of the BMJ Rapid Recommendations series. MAGICapp displays the most recent version of the guideline and full content including evidence summaries and decision aids; major updates will be published in The BMJ . We encourage re-use, adaptation and translation of these living guidelines, and recognise that the lack of availability or high costs of some medications may be prohibitive and will impact on how these recommendations are implemented across different health care systems.

ABSTRACT Ventricular arrhythmias (VA), including ventricular tachycardia and fibrillation, are critical cardiac conditions that are often managed by catheter ablation among those unresponsive to pharmacologic therapy. The choice of anesthesia and sedation regimens for VA ablations may impact arrhythmia inducibility and hemodynamic stability, which can affect procedural success and complication rates. This systematic review and meta-analysis aimed to compare the efficacy and safety of sedation versus general anesthesia (GA) among patients undergoing VA ablation. The review was prospectively registered on PROSPERO (CRD42023441553). Database searches were conducted across five major databases from inception to March 9, 2024 to identify randomized trials or observational studies including adult patients undergoing ablations for VA. Screening and data extraction were completed in duplicate. Risk-of-bias assessments were conducted using ROBINS-I as all included studies were observational, and the quality of evidence was evaluated using the GRADE framework. Six observational studies (N = 16,435) were included. No significant differences were found between sedation and GA for total procedure time (MD: −14.16 minutes; 95%CI: −38.61 to 10.29 minutes), arrhythmia non-inducibility (RR: 0.73; 95% CI: 0.33–1.58), acute ablation success (RR: 1.06; 95% CI: 0.65–1.71), or procedural complications (RR: 0.72; 95% CI: 0.28–1.85). However, sedation was associated with significantly lower intraprocedural hemodynamic instability (RR: 0.28; 95% CI: 0.12–0.70). These findings indicate that while sedation and GA have comparable outcomes, sedation may be associated with less hemodynamic instability during VA ablation. However, more high-quality studies are needed to confirm these results.

Importance The optimal inhaled reliever therapy for asthma remains unclear. Objective To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma. Data Sources The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions. Study Selection Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers). Data Extraction and Synthesis Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence. Main Outcomes and Measures Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events. Results A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], −10.3% [95% CI, −11.8% to −8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, −4.7% [95% CI, −8.0% to −1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, −5.5% [95% CI, −8.4% to −2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, −0.6% [95% CI, −1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, −1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty). Conclusions and Relevance In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

AbstractThis systematic review and meta‐analysis of randomised controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of fluvoxamine for the outpatient management of COVID‐19. We conducted this review in accordance with the PRISMA 2020 guidelines. Literature searches were conducted in MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, Web of Science, and CENTRAL up to 14 September 2023. Outcomes included incidence of hospitalisation, healthcare utilization (emergency room visits and/or hospitalisation), mortality, supplemental oxygen and mechanical ventilation requirements, serious adverse events (SAEs) and non‐adherence. Fluvoxamine 100 mg twice a day was associated with reductions in the risk of hospitalisation (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.58–0.97; I 2 = 0%) and reductions in the risk of healthcare utilization (RR 0.68, 95% CI 0.53–0.86; I 2 = 0%). While no increased SAEs were observed, fluvoxamine 100 mg twice a day was associated with higher treatment non‐adherence compared to placebo (RR 1.61, 95% CI 1.22–2.14; I 2 = 53%). In subgroup analyses, fluvoxamine reduced healthcare utilization in outpatients with BMI ≥30 kg/m2, but not in those with lower BMIs. While fluvoxamine offers potential benefits in reducing healthcare utilization, its efficacy may be most pronounced in high‐risk patient populations. The observed non‐adherence rates highlight the need for better patient education and counselling. Future investigations should reassess trial endpoints to include outcomes relating to post‐COVID sequelaes. Registration: This review was prospectively registered on PROSPERO (CRD42023463829).