Evaluating fluvoxamine for the outpatient treatment of COVID-19: A systematic review and meta-analysis.

This 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).

Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and septic shock. METHODS: We conducted a database search in MEDLINE, Embase, CENTRAL, Web of Science, and CNKI for randomised controlled trials (RCTs) comparing HAT against placebo/standard of care or against hydrocortisone in sepsis/septic shock patients. Outcomes included mortality, ICU/hospital length of stay (LOS), vasopressor durations, mechanical ventilation durations, change in SOFA at 72 h, and adverse events. RCT results were pooled in random-effects meta-analyses. Quality of evidence was assessed using GRADE. RESULTS: Fifteen RCTs (N = 2,594) were included. At 72 h, HAT reduced SOFA scores from baseline (mean difference [MD] -1.16, 95% confidence interval [CI]: -1.58 to -0.74, I2 = 0%) compared to placebo/SoC, based on moderate quality of evidence. HAT also reduced the duration of vasopressor use (MD -18.80 h, 95% CI: -23.67 to -13.93, I2 = 64%) compared to placebo/SoC, based on moderate quality of evidence. HAT increased hospital LOS (MD 2.05 days, 95% CI: 0.15-3.95, I2 = 57%) compared to placebo/SoC, based on very low quality of evidence. HAT did not increase incidence of adverse events compared to placebo/SoC. CONCLUSIONS: HAT appears beneficial in reducing vasopressor use and improving organ function in sepsis/septic shock patients. However, its advantages over hydrocortisone alone remain unclear. Future research should use hydrocortisone comparators and distinguish between sepsis-specific and comorbidity- or care-withdrawal-related mortality.

Pharmacological prevention of bone loss and fractures following solid organ transplantations: Protocol for a systematic review and network meta-analysis.

INTRODUCTION: Solid organ transplant (SOT) recipients can experience bone loss caused by underlying conditions and the use of immunosuppressants. As a result, SOT recipients are at risk for decreased bone mineral density (BMD) and increased fracture incidences. We propose a network meta-analysis (NMA) that incorporates all available randomized control trial (RCT) data to provide the most comprehensive ranking of anti-osteoporotic interventions according to their ability to decrease fracture incidences and increase BMD in SOT recipients. METHODS: We will search MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and CNKI for relevant RCTs that enrolled adult SOT recipients, assessed anti-osteoporotic therapies, and reported relevant outcomes. Title and full-text screening as well as data extraction will be performed in-duplicate. We will report changes in BMD as weighted or standardized mean differences, and fracture incidences as risk ratios. SUCRA scores will be used to provide rankings of interventions, and quality of evidence will be examined using RoB2 and CINeMA. DISCUSSIONS: To our knowledge, this systematic review and NMA will be the most comprehensive quantitative analysis regarding the management of bone loss and fractures in SOT recipients. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with SOT. The findings of the NMA will be disseminated in a peer-reviewed journal.

Efficacy and safety of selective serotonin reuptake inhibitors in COVID-19 management: a systematic review and meta-analysis.

BACKGROUND: The efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of acute COVID-19 is still under investigation, with conflicting results reported from randomized controlled trials (RCTs). Different dosing regimens may have contributed to the contradictory findings. OBJECTIVES: To evaluate the efficacy and safety of SSRIs and the effect of different dosing regimens on the treatment of acute COVID-19. DATA SOURCES: Seven databases were searched from January 2020 to December 2022. Trial registries, previous reviews, and preprint servers were hand-searched. STUDY ELIGIBILITY CRITERIA: RCTs and observational studies with no language restrictions. PARTICIPANTS: COVID-19 inpatients/outpatients. INTERVENTIONS: SSRIs prescribed after diagnosis were compared against a placebo or standard of care. ASSESSMENT OF RISK OF BIAS: Risk of bias was rated using the revised Cochrane Risk of Bias Tool for Randomized Trials version 2.0 and Risk of Bias in Non-Randomized Studies of Interventions. METHODS OF DATA SYNTHESIS: Outcomes were mortality, hospitalization, composite of hospitalization/emergency room visits, hypoxemia, requirement for supplemental oxygen, ventilator support, and serious adverse events. RCT data were pooled in random-effects meta-analyses. Observational findings were narratively described. Subgroup analyses were performed on the basis of SSRI dose, and sensitivity analyses were performed excluding studies with a high risk of bias. The Grading of Recommendations, Assessment, Development and Evaluations framework was used to assess the quality of evidence. RESULTS: Six RCTs (N = 4197) and five observational studies (N = 1156) were included. Meta-analyses associated fluvoxamine with reduced mortality (risk ratio, 0.72; 95% CI, 0.63-0.82) and hospitalization (risk ratio, 0.79; 95% CI, 0.64-0.99) on the basis of moderate quality of evidence. Medium-dose fluvoxamine (100 mg twice a day) was associated with reduced mortality, hospitalization, and composite of hospitalization/emergency room visits, but low-dose fluvoxamine (50 mg twice a day) was not. Fluvoxamine was not associated with increased serious adverse events. Observational studies support the use of fluvoxamine and highlight fluoxetine as a possible alternative to SSRIs for the treatment of COVID-19. DISCUSSION: Fluvoxamine remains a candidate pharmacotherapy for treating COVID-19 in outpatients. Medium-dose fluvoxamine may be preferable over low-dose fluvoxamine.

Prevalence of mental health symptoms in children and adolescents during the COVID-19 pandemic: A meta-analysis.

The COVID-19 pandemic and its accompanying infection control measures introduced sudden and significant disruptions to the lives of children and adolescents around the world. Given the potential for negative impacts on the mental health of youths as a result of these changes, we conducted a systematic review and meta-analysis to examine the prevalence of depressive symptoms, anxiety symptoms, and sleep disturbances in children and adolescents during the pandemic. We searched major literature databases for relevant cross-sectional or longitudinal studies that included primary and secondary school students or children and adolescents ≤18 years of age. Prevalence values were extracted, logit-transformed, and pooled. Based on 191 included studies with 1,389,447 children and adolescents, we found the pooled prevalence of depressive symptoms, anxiety symptoms, and sleep disturbances to be 31%, 31%, and 42%, respectively. Age, grade levels, education levels, gender, geographical regions, and electronics use were correlated with the prevalence of mental health symptoms. The prevalence of mental health symptoms also increased with time, although signs of recovery and stabilization were also observed. Overall, the results from this review demonstrate the need for increased mental health research, monitoring, and intervention for children and adolescents during the current and future pandemics.