Zuo, Qi Kang

Objective: To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock. Data Sources: Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched. Study Selection: Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate. Data Extraction: Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials. Data Synthesis: Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50–0.85), shorter length of hospital stay (MD: −3.76 days, 95% CI: −6.66 to −0.86), and shorter pediatric intensive care unit length of stay (MD −2.34 days, 95% CI: −3.14 to −1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence. Conclusions: While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

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).