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).

Socioeconomic differences in the impact of prices and taxes on tobacco use in low- and middle-income countries-A systematic review.

There is indisputable evidence that increases in taxes that raise tobacco prices reduce tobacco use. Consumption taxes on manufactured tobacco products, however, can be regressive in socioeconomic status (e.g., when the ratio of tax paid to income is lower for higher-income groups than for lower-income groups). Nevertheless, if the poor or less educated are more price responsive, a change in tobacco tax may be progressive in socioeconomic status. Existing reviews clearly indicate that populations with lower income or education are more responsive to tobacco tax and price changes than higher-income and more educated populations in high-income countries. Research pertaining to low- and middle-income countries was, however, limited and inconclusive. We conducted a review of quantitative studies that examined if socioeconomic status modified the association between prices and taxes and tobacco use in low- and middle-income countries. We searched two electronic databases, two search engines, and two working paper repositories. At least two reviewers independently screened articles for inclusion, extracted detailed characteristics, and assessed the risk of bias of each included study. Thirty-two studies met our inclusion criteria. Overall, we found that the evidence in low- and middle-income countries was too limited and methodologically weak to make any conclusive statements. Our review highlights a number of data and methodological limitations in existing studies. The most important limitation was the lack of formal assessment of socioeconomic differences in price responsiveness. Only seven of 32 studies assessed statistically whether own-price effects were modified by socioeconomic status. Many modelling studies have examined the distributional effect of a tax increase on tobacco use, while assuming a strong own-price elasticity gradient in income. The poor were generally assumed to be more responsive to price by a factor of two to five, relative to the wealthy. Although there are theoretical reasons to expect poorer individuals to be more responsive to monetary prices than wealthy ones in low- and middle-income countries, our review provides little empirical support.

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.

Critical appraisal of clinical practice guidelines for the management of COVID-19: protocol for a systematic review.

BACKGROUND: In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 was identified as the cause of an acute respiratory disease, coronavirus disease 2019 (COVID-19). Given the lack of validated treatments, there is an urgent need for a high-quality management of COVID-19. Clinical practice guidelines (CPGs) are one tool that healthcare providers may use to enhance patient care. As such, it is necessary that they have access to high-quality evidence-based CPGs upon which they may base decisions regarding the management and use of therapeutic interventions (TI) for COVID-19. The purpose of the proposed study is to assess the quality of CPGs that make management or TI recommendations for COVID-19 using the AGREE II instrument. METHODS: The proposed systematic review will identify CPGs for TI use and/or the management of COVID-19. The MEDLINE, EMBASE, CINAHL, and Web of Science databases, as well as the Guidelines International Network, National Institute for Health and Clinical Excellence, Scottish Intercollegiate Guidelines Network, and the World Health Organization websites, will be searched from December 2019 onwards. The primary outcome of this study is the assessed quality of the CPGs. The quality of eligible CPGs will be assessed using the Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. Descriptive statistics will be used to quantify the quality of the CPGs. The secondary outcomes of this study are the types of management and/or TI recommendations made. Inconsistent and duplicate TI and/or management recommendations made between CPGs will be compared across guidelines. To summarize and explain the findings related to the included CPGs, a narrative synthesis will also be provided. DISCUSSION: The results of this study will be of utmost importance to enhancing clinical decision-making among healthcare providers caring for patients with COVID-19. Moreover, the results of this study will be relevant to guideline developers in the creation of CPGs or improvement of existing ones, researchers who want to identify gaps in knowledge, and policy-makers looking to encourage and endorse the adoption of CPGs into clinical practice. The results of this review will be published in a peer-reviewed journal and presented at conferences. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register for Systematic Reviews (PROSPERO)- CRD42020219944.

Which Bone-Modifying Agent is Associated with Better Outcomes in Patients with Skeletal Metastases from Lung Cancer? A Systematic Review and Network Meta-analysis.

BACKGROUND: Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer-related deaths. Metastatic bone disease occurs in 20% to 40% of patients with lung cancer, and these patients often present with pain or skeletal-related events (SREs) that are associated with decreased survival. Bone-modifying agents such as denosumab or bisphosphonates are routinely used; however, to our knowledge, there has been no quantitative synthesis of randomized controlled trial data to determine the most effective pharmacologic treatment of metastatic bone disease because of lung cancer. QUESTIONS/PURPOSES: We aimed to perform a network meta-analysis of randomized trials to identify the bone-modifying agent that is associated with the (1) highest overall survival, (2) longest time to SRE, (3) lowest SRE incidence, and (4) greatest likelihood of pain resolution. METHODS: We conducted our study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and pre-registered the analysis on PROSPERO (ID: CRD42019124364). We performed a librarian-assisted search of MEDLINE, PubMed, EMBASE, Cochrane Library, and Chinese databases including China National Knowledge Infrastructure and Wanfang Data. We included randomized controlled trials reporting outcomes specifically for patients with lung cancer treated with a bisphosphonate or denosumab. SREs included pathologic fractures, spinal cord compression, hypercalcemia of malignancy, or pain resulting in surgical intervention or radiation therapy. We excluded trials exclusively reporting surrogate outcomes such as changes in bone turnover markers. Screening, data extraction, risk of bias evaluation, and Grading of Recommendations Assessment, Development, and Evaluation evaluations were performed in duplicate. We included 131 randomized controlled trials that evaluated 11,105 patients with skeletal metastases from lung cancer. The network meta-analysis was performed using a frequentist model and the R statistical software. Results are reported as relative risks or mean differences, and the I2 value is reported for heterogeneity. The P-score, a measure of ranking certainty that accounts for standard error, is reported for each outcome. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for the incidence of SRE, and low for pain resolution. RESULTS: For overall survival, denosumab was ranked above zoledronic acid and estimated to confer a mean of 3.3 months (95% CI 0.3-6.3) of increased overall survival compared with untreated patients (P-score = 89%). For the time to SRE, denosumab was ranked first with a mean of 9.1 additional SRE-free months (95% CI 6.7-11.5) compared with untreated patients (P-score = 99%), while zoledronic acid conferred an additional 4.8 SRE-free months (95% CI 3.6-6.1). Reduction in the incidence of SREs was not different between patients treated with denosumab (relative risk 0.54; 95% CI 0.33-0.87) and those treated with zoledronic acid (relative risk 0.56; 95% CI 0.46-0.67). Patients treated with the combination of ibandronate and systemic therapy were more likely to experience successful pain resolution than untreated patients (relative risk 2.4; 95% CI 1.8-3.2). CONCLUSION: In this comprehensive synthesis of all available randomized controlled trial evidence guiding the pharmacologic treatment of bone metastases from lung cancer, denosumab was ranked above zoledronic acid for overall survival and time to SRE and was not different for reducing the incidence of SRE. Both were superior to no treatment for each of these outcomes. Given this, we encourage physicians to consider the use of denosumab or zoledronic acid in treating this patient population. The combination of ibandronate and systemic therapy was the most effective at reducing pain because of metastases. No cost-effectiveness analysis has yet been performed for denosumab and zoledronic acid on patients with metastatic lung cancer, and this represents an avenue for future research. LEVEL OF EVIDENCE: Level I, therapeutic study.

Antidiabetic and antiosteoporotic pharmacotherapies for prevention and treatment of type 2 diabetes-induced bone disease: protocol for two network meta-analyses.

INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) are at risk for a variety of severe debilitating effects. One of the most serious complications experienced by patients with T2DM are skeletal diseases caused by changes in the bone microenvironment. As a result, patients with T2DM are at risk for higher prevalence of fragility fractures. There are a variety of treatments available for counteracting this effect. Some antidiabetic medications, such as metformin, have been shown to have a positive effect on bone health without the addition of additional drugs into patients' treatment plans. Chinese randomised controlled trial (RCT) studies have also proposed antiosteoporotic pharmacotherapies as a viable alternative treatment strategy. Previous network meta-analyses (NMAs) and meta-analyses regarding this topic did not include all available RCT trials, or only performed pairwise comparisons. We present a protocol for a two-part NMA that incorporates all available RCT data to provide the most comprehensive ranking of antidiabetics (part I) and antiosteoporotic (part II) pharmacotherapies in terms of their ability to decrease fracture incidences, increase bone mineral density (BMD) and improve indications of bone turnover markers (BTMs) in adult patients with T2DM. METHODS AND ANALYSIS: We will search Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials and Chinese literature sources (China National Knowledge Infrastructure, Chongqing VIP Information, Wanfang Data, Wanfang Med Online) for RCTs, which fit our criteria. We will include adult patients with T2DM who have taken antidiabetics (part I) or antiosteoporotic (part II) therapies with relevant outcome measures in our study. We will perform title/abstract and full-text screening as well as data extraction in duplicate. Risk of bias will be evaluated in duplicate for each study, and the quality of evidence will be examined using Confidence in Network Meta-Analysis in accordance to the Grading of Recommendations Assessment, Development and Evaluation framework. We will use R and gemtc to perform the NMA. We will report changes in BMD and BTMs in either weighted or standardised mean difference, and we will report fracture incidences as ORs. We will use the Surface Under the Cumulative Ranking Curve scores to provide numerical estimates of the rankings of interventions. ETHICS AND DISSEMINATION: The study will not require ethics approval. The findings of the two-part NMA will be disseminated in peer-reviewed journals and presented at conferences. We aim to produce the most comprehensive quantitative analysis regarding the management of T2DM bone disease. Our analysis should be able to provide physicians and patients with up-to-date recommendations for antidiabetic medications and antiosteoporotic pharmacotherapies for maintaining bone health in patients with T2DM. PROSPERO REGISTRATION NUMBER: CRD42019139320.