scholarly journals Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cathrine Axfors ◽  
Andreas M. Schmitt ◽  
Perrine Janiaud ◽  
Janneke van’t Hooft ◽  
Sherief Abd-Elsalam ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Total Sample ◽  
Recruitment Challenges ◽  
Chloroquine Treatment ◽  
All Cause Mortality ◽  
High Doses ◽  
Meta Analyses ◽  
Clinical Trials Registry

AbstractSubstantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

scholarly journals Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials

2020 ◽  
Author(s):  
Cathrine Axfors ◽  
Andreas M. Schmitt ◽  
Perrine Janiaud ◽  
Janneke van ’t Hooft ◽  
Sherief Abd-Elsalam ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Total Sample ◽  
Recruitment Challenges ◽  
Included Patient ◽  
Chloroquine Treatment ◽  
All Cause Mortality ◽  
High Doses ◽  
Meta Analyses

AbstractSubstantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We conducted a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine was 1.11 (95% CI: 1.02, 1.20; I2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine was associated with increased mortality in COVID-19 patients, and there was no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

scholarly journals Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Steven Kwasi Korang ◽  
Sophie Juul ◽  
Emil Eik Nielsen ◽  
Joshua Feinberg ◽  
Faiza Siddiqui ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Individual Patient Data ◽  
Viral Vector ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Serious Adverse Events ◽  
Meta Analyses ◽  
Harmful Effects

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19. Methods/design We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; “active placebo;” no intervention; standard care; an “active” intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately. Discussion COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease. Systematic review registration PROSPERO CRD42020196492

scholarly journals Intentional Weight Loss and All-Cause Mortality: A Meta-Analysis of Randomized Clinical Trials

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0121993 ◽  
Author(s):  
Stephen B. Kritchevsky ◽  
Kristen M. Beavers ◽  
Michael E. Miller ◽  
M. Kyla Shea ◽  
Denise K. Houston ◽  
...  
Keyword(s):  
Weight Loss ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Intentional Weight Loss ◽  
All Cause Mortality

Efficacy of acupuncture in the management of fatigue related to breast cancer antineoplastic treatment: a systematic review

2019 ◽  
Vol 9 (2) ◽  
pp. 264-272
Author(s):  
Ana Carolina Moraes Costa ◽  
Alena Peixoto Medrado
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Scientific Evidence ◽  
Total Sample ◽  
Inclusion Criteria ◽  
Antineoplastic Treatment

INTRODUCTION: Breast cancer is the most prevalent cancer among women worldwide. Similar to chemotherapy, antineoplastic treatment is associated with many side effects, with fatigue being one of the most common. It is important to investigate potential treatments, especially non-pharmacological alternatives, to control symptoms that directly affect women’s quality of life. OBJECTIVE: The objective of this study was to provide scientific evidence to verify the efficacy of acupuncture in the management of fatigue in patients with breast cancer. METHODS: This study involved a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology. Randomized clinical trials published in indexed scientific journals were compiled. The literature search was performed using the electronic databases, PubMed, PEDro, and BIREME, using the descriptors ‘breast cancer’, ‘fatigue’, ‘acupuncture’, and ‘randomized trial’. Inclusion criteria included fully available online articles that were classified as randomised clinical trials published from 2012 to 2017 in either English or Portuguese. Study eligibility was based on the Population, Intervention, Control, Outcome, and Study (PICO) design criteria, in which the (1) population included women 18–65 years of age with breast cancer, (2) intervention was acupuncture, (3) comparison referred to standard care or sham acupuncture, and (4) outcome was the evaluation of fatigue. The PEDro scale was applied to evaluate the quality of the studies. WebQualis was also used to evaluate the quality of the journals of the selected articles. RESULTS: In total, 66 articles were selected, but only four fulfilled all inclusion criteria, giving a total sample size of 620 women. All trials evaluated the effect of acupuncture on fatigue and other symptoms related to the treatment of breast cancer with different treatment durations. Three articles reported statistically significant results, and all articles described clinical improvement in fatigue after the application of acupuncture. The average PEDro score of the manuscripts was 6.25. All articles were published in non-Brazilian journals with WebQualis scores that ranged from B2 to A1. CONCLUSION: Scientific evidence confirms the efficacy of acupuncture in the management of fatigue reported by women with breast cancer. Acupuncture was effective in reducing fatigue in the studies selected for this review.

scholarly journals Efficacy of Adjunctive Treatments Added to Olanzapine or Clozapine for Weight Control in Patients with Schizophrenia: A Systematic Review and Meta-Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yun-Jung Choi
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Effects ◽  
Weight Reduction ◽  
Weight Control ◽  
Randomized Clinical Trials ◽  
Psychiatric Symptoms ◽  
Meta Analysis ◽  
Cochrane Central Register ◽  
Meta Analyses

Objectives. This study was conducted to review systematically adjunctive treatments for weight reduction in patients with schizophrenia and compare efficacies of clinical trials through meta-analysis, so as to provide effective clinical guideline regarding weight control for patients taking atypical antipsychotics.Methods. Candidate clinical trials were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO. Fourteen randomized clinical trials were included for systematic review and meta-analysis from 132 potential trials. The Comprehensive Meta-Analysis version 2 was used for meta-analysis.Results. Difference in means and significances from meta-analyses regarding weight control by adjunctive treatments showed that topiramate, aripiprazole, or sibutramine was more effective than metformin or reboxetine. Psychiatric evaluations did not show statistically significant changes between treatment groups and placebo groups except topiramate adjunctive treatments. Adverse effects regarding adjunctive therapies were tolerable and showed statistically no significances compared to control groups.Conclusion. Though having several reports related to exacerbation of psychiatric symptoms, topiramate and aripiprazole are more efficacious than other medications in regard to weight reduction and less burden of critical adverse effects as well as being beneficial for clinical improvement.

scholarly journals A Systematic Review and Network Meta-Analysis on the Efficacy of Medications in the Treatment of Chronic Idiopathic Constipation in Japan

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Atsushi Nakajima ◽  
Ayako Shoji ◽  
Kinya Kokubo ◽  
Ataru Igarashi
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Bayesian Network ◽  
Systematic Reviews ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Relative Efficacy ◽  
Idiopathic Constipation ◽  
Chronic Idiopathic Constipation ◽  
Meta Analyses

Background. In the 2010s, medications with new mechanisms were introduced in Japan for the treatment of chronic idiopathic constipation (CIC). A few systematic reviews have compared medications’ relative efficacy, but the reviews included studies on patients from various races, even though the mechanism of CIC is considered to differ between races. The aim of this study was to use a systematic review and network meta-analysis to compare the relative efficacy of these medications in Japanese patients. Methods. We conducted a meta-analysis and report it here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified studies by searching MEDLINE (via the PubMed interface) and the Cochrane Library and ICHUSHI databases and included randomized clinical trials that compared medications for CIC with placebo in Japanese adults. Two reviewers independently screened and assessed articles, abstracted data, and assessed the risk of bias. We pooled data by random-effects meta-analyses and also performed a Bayesian network meta-analysis to indirectly compare data. Results. The present systematic review and meta-analyses included 1460 patients in 6 randomized clinical trials: 2 on linaclotide, 3 on elobixibat, 2 on lubiprostone, and 1 on lactulose. The results of direct comparisons showed that linaclotide, elobixibat, and lubiprostone were superior to placebo in the change of spontaneous bowel movements (SBMs) within 1 week: linaclotide, 1.95 (95% CI, 1.51-2.39); elobixibat, 5.69 (95% CI, 3.31-8.07); and lubiprostone, 2.41 (95% CI, 0.82-4.01). The Bayesian network meta-analysis showed consistent results. Elobixibat 10 mg was ranked first for the increase in SBMs and complete SBMs within 1 week and the time to first SBM. Lubiprostone 48 μg was ranked first for the proportion of patients with SBM within 24 hours. Conclusion. Our direct and indirect meta-analyses revealed that the new CIC medications available in Japan have equal efficacy but that elobixibat and lubiprostone are highly likely to be more efficacious.

Cardiovascular toxicity incidence following immune checkpoint inhibitors in randomized clinical trials: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2636-2636
Author(s):  
Camila Bragança Xavier ◽  
Carlos Diego Holanda Lopes ◽  
Guilherme Harada ◽  
Artur Katz ◽  
Denis Leonardo Fontes Jardim
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Increased Risk ◽  
Meta Analyses

2636 Background: Immune checkpoint inhibitors (ICIs) are widely used in oncology and may be associated with a variety of immune-related toxicities. Cardiovascular (CV) adverse effects (AEs) are underreported in randomized clinical trials (RCTs), and the real risk associated with ICIs use has yet to be defined. Therefore, we aimed to investigate the incidence and risk of cardiovascular toxicities in patients receiving ICIs, using an up-to-date meta-analysis of prospective RCTs. Methods: We conducted a systematic search of the literature from January 1st, 2010 until July 1st, 2020 to identify RCTs testing ICIs for solid tumors, either in monotherapy or in combination between them. Our initial search yielded a total of 21,249 relevant publications. For CV AEs incidence estimation, we included phase III RCTs testing PD-1, PD-L1, CTLA-4 inhibitors or any combination of these agents. For relative risk (RR) assessment, we included phase II or phase III RCTs testing the same agents and with placebo or best supportive care (BSC) as the comparator. Data were extracted by independent reviewers following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. CV AEs were categorized based on the Common Toxicity Criteria (CTCAE) and stratified by ICIs type. Analyses were conducted using random effects model. Results: After screening and eligibility assessment, a total of 21,118 patients (67 cohorts from 57 trials) were available for this meta-analysis. We categorized the cohorts by ICIs regimen as monotherapy with a PD-1 inhibitor (35 cohorts; 10,241 patients), PD-L1 inhibitor (12 cohorts; 3,755 patients), CTLA-4 inhibitor (11 cohorts; 4,135 patients), and combination therapy (9 cohorts; 2,987 patients). Incidence measures are described in the table. Deaths from any CV cause occurred in 0.20% of the patients (95%CI 0.10%; 0.20%). For RR analysis, we included 12 cohorts from 11 RCTs. Risk of experiencing all grade AEs was numerically higher among patients who received ICIs than placebo or BSC (RR 1.16; 95%CI 0.98; 1.37; p=0.09). When only grade 3-5 CV AEs were considered, ICIs were associated with increased risk (RR 1.36; 95%CI 1.06; 1.73; p= 0.01). Additional analyses were conducted to estimate the RR of individual CV AEs including arrhythmia, cardiac arrest, heart failure, stroke, hypertension, myocardial infarction, myocarditis, pericardial events, and thromboembolic events. None of the analysis identified a significant additional risk. Conclusions: This meta-analysis corroborates the preclinical rationale of worsen CV risk related to ICIs use.[Table: see text]

scholarly journals Randomized Clinical Trials of Constitutional Acupuncture: A Systematic Review

2009 ◽  
Vol 6 (s1) ◽  
pp. 59-64 ◽  
Author(s):  
Myeong Soo Lee ◽  
Byung-Cheul Shin ◽  
Sun-Mi Choi ◽  
Jong Yeol Kim
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Rating Scale ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Total Sample ◽  
Pain Reduction ◽  
Population Characteristics ◽  
Constitutional Medicine

The aim of this systematic review is to compile and critically evaluate the evidence from randomized clinical trials (RCTs) for the effectiveness of acupuncture using constitutional medicine compared to standard acupuncture. Ten databases were searched through to December 2008 without language restrictions. We also hand-searched nine Korean journals of oriental medicine. We included prospective RCTs of any form of acupuncture with or without electrical stimulation. The included trials had to investigate constitutional medicine. There were no restrictions on population characteristics. Forty-one relevant studies were identified, and three RCTs were included. The methodological quality of the trials was variable. One RCT found Sasang constitutional acupuncture to be superior to standard acupuncture in terms of the Unified PD Rating Scale and freezing gate in Parkinson's disease (PD). Another two RCTs reported favorable effects of eight constitutional acupuncture on pain reduction in patients with herniated nucleus pulposi and knee osteoarthritis. Meta-analysis demonstrated positive results for eight constitutional acupuncture compared to standard acupuncture on pain reduction (weighted mean difference: 10 cm VAS, 1.69, 95% CI 0.85–2.54,P< 0.0001; heterogeneity: τ2= 0.00, Χ2= 0.00,P= 0.96, I2= 0%). Our results provide suggestive evidence for the effectiveness of constitutional acupuncture in treating pain conditions compared to standard acupuncture. However, the total number of RCTs and the total sample size included in our analysis were too small to draw definite conclusions. Future RCTs should assess larger patient samples with longer treatment periods and appropriate controls.

scholarly journals A Method to Estimate the Efficacy vs Effectiveness in Meta-Analysis of Clinical Trials with Different Adherence Scenarios: A Monte Carlo Simulation Study in Nutrition

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2352
Author(s):  
Miguel Ángel López-Espinoza ◽  
José Antonio Lozano-Lozano ◽  
David Prieto-Merino
Keyword(s):  
Clinical Trials ◽  
Monte Carlo ◽  
Randomized Clinical Trials ◽  
Expert Knowledge ◽  
Meta Analysis ◽  
Specific Effect ◽  
Cochrane Systematic Review ◽  
Monte Carlo Simulation Study ◽  
Intention To Treat ◽  
Meta Analyses

Randomized clinical trials (RCTs) evaluating the effectiveness of interventions to promote fruit and vegetable (FV) consumption usually report intention-to-treat (ITT) analysis as the main outcome. These analyses compare the randomly assigned groups and accept that some individuals may not follow the recommendations received in their group. The ITT analysis is useful to quantify the global effect of promoting the consumption of FV in a population (effectiveness) but, if non-adherence is significant in the RCT, they cannot estimate the specific effect in the individuals that increased their FV consumption (efficacy). To calculate the efficacy of FV consumption, a per protocol analysis (PP) would have to be carried out, in which groups of individuals are compared according to their actual adherence to FV consumption, regardless of the group to which they were assigned; unfortunately, many RCTs do not report the PP analysis. The objective of this article is to apply a new method to estimate the efficacy of Meta-analysis (MA) PP which include RCTs of effectiveness by ITT, without estimates of adherence. The method is based on generating Monte Carlo simulations of percentages of adherence in each allocation group from prior distributions informed by expert knowledge. We illustrate the method reanalyzing a Cochrane Systematic Review (SR) of RCTs on increased FV consumption reported with ITT, simulating 1000 times the estimation of a PP meta-analyses, and obtaining means and ranges of the potential PP effects. In some cases, the range of estimated PP effects was clearly more favourable than the effect calculated with the original ITT assumption, and therefore this corrected analysis must be considered when estimating the true effect of the consumption of a certain food.

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