scholarly journals Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis

PLoS Medicine ◽  
2020 ◽  
Vol 17 (12) ◽  
pp. e1003501
Author(s):  
Min Seo Kim ◽  
Min Ho An ◽  
Won Jun Kim ◽  
Tae-Ho Hwang
Keyword(s):  
Mortality Rate ◽  
Observational Studies ◽  
Standard Care ◽  
Meta Analysis ◽  
Cardiac Complications ◽  
Comparative Efficacy ◽  
Pharmacological Interventions ◽  
Level Of Evidence ◽  
Serious Adverse Events ◽  
Pharmacological Management

Background Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but the results are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective. Methods and findings We carried out a systematic review and network meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological interventions and the level of evidence behind each treatment regimen in different clinical settings. Both published and unpublished randomized controlled trials (RCTs) and confounding-adjusted observational studies which met our predefined eligibility criteria were collected. We included studies investigating the effect of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require hospitalization or have self-limiting disease courses were not eligible for our NMA. A total of 110 studies (40 RCTs and 70 observational studies) were included. PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from the beginning of 2020 to August 24, 2020. Studies from Asia (41 countries, 37.2%), Europe (28 countries, 25.4%), North America (24 countries, 21.8%), South America (5 countries, 4.5%), and Middle East (6 countries, 5.4%), and additional 6 multinational studies (5.4%) were included in our analyses. The outcomes of interest were mortality, progression to severe disease (severe pneumonia, admission to intensive care unit (ICU), and/or mechanical ventilation), viral clearance rate, QT prolongation, fatal cardiac complications, and noncardiac serious adverse events. Based on RCTs, the risk of progression to severe course and mortality was significantly reduced with corticosteroids (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06 to 0.86, p = 0.032, and OR 0.78, 95% CI 0.66 to 0.91, p = 0.002, respectively) and remdesivir (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (OR 0.54, 95% CI 0.40 to 0.73, p < 0.001) for critically ill patients in ICU. In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients. Convalescent plasma was the only treatment option that was associated with improved viral clearance rate at 2 weeks compared to standard care (OR 11.39, 95% CI 3.91 to 33.18, p < 0.001). The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 2.01, 95% CI 1.26 to 3.20, p = 0.003) and fatal cardiac complications in cardiac-impaired populations (OR 2.23, 95% CI 1.24 to 4.00, p = 0.007). No drug was significantly associated with increased noncardiac serious adverse events compared to standard care. The quality of evidence of collective outcomes were estimated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The major limitation of the present study is the overall low level of evidence that reduces the certainty of recommendations. Besides, the risk of bias (RoB) measured by RoB2 and ROBINS-I framework for individual studies was generally low to moderate. The outcomes deducted from observational studies could not infer causality and can only imply associations. The study protocol is publicly available on PROSPERO (CRD42020186527). Conclusions In this NMA, we found that anti-inflammatory agents (corticosteroids, tocilizumab, anakinra, and IVIG), convalescent plasma, and remdesivir were associated with improved outcomes of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac safety risks when combined with azithromycin, especially in the vulnerable population. Only 29% of current evidence on pharmacological management of COVID-19 is supported by moderate or high certainty and can be translated to practice and policy; the remaining 71% are of low or very low certainty and warrant further studies to establish firm conclusions.

scholarly journals Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis of confounder-adjusted 20212 hospitalized patients

2020 ◽  
Author(s):  
Min Seo Kim ◽  
Min Ho An ◽  
Won Jun Kim ◽  
Tae-Ho Hwang
Keyword(s):  
Systematic Review ◽  
Severe Pneumonia ◽  
Viral Clearance ◽  
Current Evidence ◽  
Cardiac Complications ◽  
High Dose ◽  
List Type ◽  
Level Of Evidence ◽  
Serious Adverse Events ◽  
Pharmacological Management

ABSTRACTObjectiveTo evaluate the comparative efficacy and safety of pharmacological interventions used in treating COVID-19 and form a basis for an evidence-based guideline of COVID-19 management by evaluating the level of evidence behind each treatment regimen in different clinical settings.DesignSystematic review and network meta-analysisData SourcesPubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov up to June 9th, 2020.Study SelectionPublished and unpublished randomized controlled trials (RCTs) and baseline-adjusted observational studies which met our predefined eligibility criteria.Main Outcome MeasuresThe outcomes of interest were mortality, progression to severe disease (severe pneumonia or admission to intensive care unit (ICU)), time to viral clearance, QT prolongation, fatal cardiac complications, and non-cardiac serious adverse events. The level of evidence behind each outcome was also measured using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Results49 studies with a total of 20212 confounder-adjusted patients were included for analysis. The risk of progression to severe pneumonia or ICU admission was significantly reduced with tocilizumab (GRADE low), anakinra (GRADE very low), and remdesivir (GRADE high) compared to standard care. Tocilizumab was shown to reduce mortality rate for both moderate-severe patients in the non-ICU setting at admission (Odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18 to 0.54, GRADE low) and critically ill patients in the ICU setting (OR 0.67, 95% CI 0.50 to 0.91, GRADE low). High dose IVIG reduced death rate (GRADE low) while corticosteroids increased mortality for critically ill patients (GRADE moderate). Convalescent plasma and hydroxychloroquine were shown to promote viral clearance (OR 11.39, 95% CI 3.91 to 33.18, GRADE low and OR 6.08, 95% CI 2.74 to 13.48, GRADE moderate, respectively) while not altering mortality or progression to the severe courses. The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 1,85, 95% CI 1.05 to 3.26, GRADE low) and fatal cardiac complications in cardiac-impaired populations (OR 2.26, 95% CI 1.26 to 4.05, GRADE low). High-dose (>600mg/day) hydroxychloroquine monotherapy was significantly associated with increased non-cardiac serious adverse events (GRADE moderate).ConclusionAnti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve outcomes of hospitalized COVID-19 patients. Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks, especially in the vulnerable population. Only 20% of current evidence on pharmacological management of COVID-19 is on moderate and high evidence certainty and can be considered in practice and policy; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions.Systematic Review RegistrationPROSPERO 2020: CRD42020186527.Summary BoxSection 1: What is already known on this topic-Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for COVID-19.-Results from numerous studies are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective.-Level of evidence behind each outcome from diverse studies remains unknown.Section 2: What this study adds-Anti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve clinical outcomes of COVID-19.-Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks.-Only 20% of current evidence on pharmacological management of COVID-19 is on moderate/high evidence certainty and can be considered in practice and policy; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions.

scholarly journals Pharmacological interventions for drug-using offenders: an update to a systematic review and meta-analysis

2021 ◽  
Author(s):  
J. M. Glanville ◽  
A. E. Perry ◽  
M. Martyn-St James ◽  
C. Hewitt ◽  
S. Swami ◽  
...  
Keyword(s):  
Systematic Review ◽  
Drug Use ◽  
Meta Analysis ◽  
Treatment Options ◽  
Criminal Activity ◽  
Cochrane Collaboration ◽  
Pharmacological Interventions ◽  
Serious Adverse Events ◽  
Male Adult ◽  
The Impact

Abstract This updated systematic review assesses the effects of pharmacological interventions for drug-using offenders. Methods Systematic review protocols and conventions of the Cochrane Collaboration were followed to identify eligible studies. Studies were pooled in a meta-analysis to assess the impact of pharmacological interventions on drug use and criminal activity. An economic appraisal was conducted. Results The search strategies identified 22 studies containing 4372 participants. Meta-analyses revealed a small statistically significant mean difference favouring pharmacological interventions relative to psychological interventions in reducing drug use and criminal activity. When comparing the drugs to one another there were no significant differences between those included (methadone versus buprenorphine, naltrexone and cyclazocine). Conclusion Overall, the findings of this review suggest that methadone and naltrexone may have some impact on reducing drug use and reincarceration. Individual pharmacological drugs had differing (generally non-significant) effects. One study identified serious adverse events. Three studies reported cost and consequences information sufficient to conduct a full economic analysis but this was not comprehensive enough to be able to make judgements across all treatment options. Full economic analyses should be encouraged. The study findings were limited mainly to male adult offenders.

scholarly journals Cardiac Complications in Patients with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Observational Studies

PLoS Medicine ◽  
2011 ◽  
Vol 8 (6) ◽  
pp. e1001048 ◽  
Author(s):  
Vicente F. Corrales-Medina ◽  
Kathryn N. Suh ◽  
Gregory Rose ◽  
Julio A. Chirinos ◽  
Steve Doucette ◽  
...  
Keyword(s):  
Systematic Review ◽  
Observational Studies ◽  
Meta Analysis ◽  
Community Acquired Pneumonia ◽  
Cardiac Complications

Antenatal corticosteroids in impending preterm deliveries before 25 weeks’ gestation

2017 ◽  
Vol 103 (2) ◽  
pp. F173-F176 ◽  
Author(s):  
Mangesh Deshmukh ◽  
Sanjay Patole
Keyword(s):  
Observational Studies ◽  
Meta Analysis ◽  
Periventricular Leukomalacia ◽  
Intraventricular Haemorrhage ◽  
Random Effects Model ◽  
Antenatal Corticosteroids ◽  
Level Of Evidence ◽  
Previous Systematic Review ◽  
Assessment Development ◽  
Low Incidence

Antenatal corticosteroid (ANC) use before 25 weeks’ gestation is controversial. Our previous systematic review (eight observational studies, n=10 109) showed that ANC exposure was associated with significantly reduced mortality and severe intraventricular haemorrhage (IVH)/periventricular leukomalacia (PVL) in neonates born <25 weeks. We update our review by adding data (n=3334) from a recent study. We used Cochrane methodology and summarised the results using GRADE (The Grading of Recommendations Assessment, Development and Evaluation) guidelines. Nine high-quality observational studies were included. Meta-analysis (random effects model) showed reduced mortality (n=13 443; OR=0.48 (95% CI 0.42 to 0.55) P<0.00001; level of evidence (LOE): moderate) and IVH or PVL (n=8418; OR=0.70 (95% CI 0.63 to 0.79), P<0.00001; LOE: moderate) in neonates born <25 weeks exposed to ANC. There was no difference in necrotising enterocolitis (NEC) ≥stage II (n=8737; OR=1.01 (95% CI 0.84 to 1.22), P=0.89; LOE: low); incidence of chronic lung disease (CLD) was higher (n=7983; OR=1.32 (95% CI 1.04 to 1.67), P=0.02; LOE: low) in ANC group. Composite outcomes of death/major morbidities (eg, severe IVH, NEC, CLD) were improved after ANC exposure.

383 Comparative Efficacy and Tolerability of Long-Term Pharmacological Interventions for Obesity: A Systematic Review and Network Meta-Analysis

2016 ◽  
Vol 150 (4) ◽  
pp. S87
Author(s):  
Rohan Khera ◽  
Mohammad H. Murad ◽  
Apoorva K. Chandar ◽  
Parambir S. Dulai ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Comparative Efficacy ◽  
Pharmacological Interventions

scholarly journals Effectiveness and Safety of Remdesivir in Patients with COVID-19: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Hai-Bo Yao ◽  
Jie-Ru Peng ◽  
Xue-Mei Zheng ◽  
Zhuo Yang ◽  
Huang Yan ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Improvement ◽  
Observational Studies ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Antiviral Drug ◽  
Serious Adverse Events ◽  
Effect Model ◽  
Grade 3

Abstract Background: Remdesivir, a nucleoside analogue antiviral drug developed for Ebola, is approved by the US Food and Drug Administration for the treatment of COVID-19. However, the findings of randomised controlled trials (RCTs) and observational studies vary regarding the effectiveness of remdesivir. We aimed to comprehensively review the available evidence identify the effectiveness and safety of remdesivir in patients with COVID-19.Methods: Seven databases (PubMed, Web of Science, Embase, Wanfang database, SinoMed, Chinese National Knowledge Infrastructure and Chinese Science Journal Database) were searched for literatures published until November 2020.Following the PRISMA flow diagram, we included RCTs and prospective observational studies that reported the effectiveness and safety of remdesivir in patients with COVID-19. With extracting study details, as well as patient characteristics and outcomes, data were meta-analyzed by using Review Manager software version 5.4.1. Meta-analyses were conducted with fixed-effect model or random-effect model to calculate risk ratio (RR).Results: Four studies involving 2,279 patients were included in this meta-analysis. Compared with placebo, 10-day remdesivir was associated with significant increased clinical improvement on days 14 and 28 with RR 1.19 (95%CI 1.09-1.30) and RR 1.09 (95%CI 1.03-1.16). The clinical improvement of 5-day remdesivir was better than 10-day remdesivir on days 7 with RR 1.20 (95%CI 1.02-1.41), but the efficacy advantage of 5-day remdesivir disappeared on days 14 (RR 1.08; 95%CI 0.90-1.29). Remdesivir was associated with lower serious adverse events rates and grade 3 or 4 adverse events rates as compared with placebo with RR 0.75(95%CI 0.63-0.89) and RR 0.89(95%CI 0.80-0.99). Compared with 10-day remdesivir, 5-day remdesivir for patients with COVID-19 decreased the risk of serious adverse events rates and grade 3 or 4 adverse events rates with RR 0.65(95%CI 0.47-0.88) and RR 0.74 (95%CI 0.58-0.95). Conclusions: Our meta-analysis suggested that remdesivir would increase clinical improvement conditions and decrease serious adverse events on patients with COVID-19. 5-day remdesivir had the similar clinical effectiveness and mortality with 10-day remdesivir, and had lower serious adverse events rate. Comprehensive considering the cost and benefit, 5-day remdesivir may be a better therapeutic option if available medical resources are limited.

scholarly journals Cardiovascular Events after Community-Acquired Pneumonia: A Global Perspective with Systematic Review and Meta-Analysis of Observational Studies

2020 ◽  
Vol 9 (2) ◽  
pp. 414 ◽  
Author(s):  
António Tralhão ◽  
Pedro Póvoa
Keyword(s):  
Heart Failure ◽  
Acute Coronary Syndromes ◽  
Cardiovascular Events ◽  
Observational Studies ◽  
Meta Analysis ◽  
Community Acquired Pneumonia ◽  
Cardiac Complications ◽  
Short Term ◽  
Short Term Mortality ◽  
Coronary Syndromes

Acute cardiovascular disease after community-acquired pneumonia is a well-accepted complication for which definitive treatment strategies are lacking. These complications share some common features but have distinct diagnostic and treatment approaches. We therefore undertook an updated systematic review and meta-analysis of observational studies reporting the incidence of overall complications, acute coronary syndromes, new or worsening heart failure, new or worsening arrhythmias and acute stroke, as well as short-term mortality outcomes. To set a framework for future research, we further included a holistic review of the interplay between the two conditions. From 1984 to 2019, thirty-nine studies were accrued, involving 92,188 patients, divided by setting (inpatients versus outpatients) and clinical severity (low risk versus high risk). Overall cardiac complications occurred in 13.9% (95% confidence interval (CI) 9.6–18.9), acute coronary syndromes in 4.5% (95% CI 2.9–6.5), heart failure in 9.2% (95% CI 6.7–12.2), arrhythmias in 7.2% (95% CI 5.6–9.0) and stroke in 0.71% (95% CI 0.1–3.9) of pooled inpatients. During this period, meta-regression analysis suggests that the incidence of overall and individual cardiac complications is decreasing. After adjusting for confounders, cardiovascular events taking place after community-acquired pneumonia independently increase the risk for short-term mortality (range of odds-ratio: 1.39–5.49). These findings highlight the need for effective, large trial based, preventive and therapeutic interventions in this important patient population.

Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis

2020 ◽  
pp. bmjspcare-2020-002601
Author(s):  
Manit Saeteaw ◽  
Phitjira Sanguanboonyaphong ◽  
Jukapun Yoodee ◽  
Kaitlyn Craft ◽  
Ratree Sawangjit ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Total Body Weight ◽  
Megestrol Acetate ◽  
High Dose ◽  
Efficacy And Safety ◽  
Pharmacological Interventions ◽  
Serious Adverse Events ◽  
Significant Difference

AimsRandomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia.MethodsPubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI.Results80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (≥400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (≥400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo.ConclusionsOur findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.

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