scholarly journals Assessment of Hydroxychloroquine and Chloroquine Safety Profiles – A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Lu Ren ◽  
Wilson Xu ◽  
James L Overton ◽  
Shandong Yu ◽  
Nipavan Chiamvimonvat ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Regression Analyses ◽  
Inclusion Criteria ◽  
Randomized Controlled ◽  
Central Register ◽  
Precautionary Measures ◽  
Meta Analyses

AbstractBackgroundRecently, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have emerged as potential antiviral and immunomodulatory options for the treatment of 2019 coronavirus disease (COVID-19). To examine the safety profiles of these medications, we systematically evaluated the adverse events (AEs) of these medications from published randomized controlled trials (RCTs).MethodsWe systematically searched PubMed, MEDLINE, Cochrane, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, and the ClinicalTrials.gov for all the RCTs comparing CQ or HCQ with placebo or other active agents, published before March 31, 2020. The random-effects or fixed-effects models were used to pool the risk estimates relative ratio (RR) with 95% confidence interval (CI) for the outcomes.ResultsThe literature search yielded 23 and 17 studies for CQ and HCQ, respectively, that satisfied our inclusion criteria. Of these studies, we performed meta-analysis on the ones that were placebo-controlled, which included 6 studies for CQ and 14 studies for HCQ. We did not limit our analysis to published reports involving viral treatment alone; data also included the usage of either CQ or HCQ for the treatment of other diseases. The trials for the CQ consisted of a total of 2,137 participants (n=1,077 CQ, n=1,060 placebo), while the trials for HCQ involved 1,096 participants (n=558 HCQ and n=538 placebo). The overall mild or total AEs were statistically higher comparing CQ or HCQ to placebo. The AEs were further categorized into four groups and analyses revealed that neurologic, gastrointestinal, dermatologic, and ophthalmic AEs were higher in participants taking CQ compared to placebo. Although this was not evident in HCQ treated groups, further analyses suggested that there were more AEs attributed to other organ system that were not included in the categorized meta-analyses. Additionally, meta-regression analyses revealed that total AEs was affected by dosage for the CQ group.ConclusionsTaken together, we found that participants taking either CQ or HCQ have more AEs than participants taking placebo. Precautionary measures should be taken when using these drugs to treat COVID-19.

Febuxostat use and risks of CVD events, death from cardiac-cause and all-cause mortality: metaanalysis of randomized controlled trials

2020 ◽  
pp. jrheum.200307
Author(s):  
Hao Deng ◽  
Bao Long Zhang ◽  
Jin Dong Tong ◽  
Xiu Hong Yang ◽  
Hui Min Jin
Keyword(s):  
Web Of Science ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Inclusion Criteria ◽  
Randomized Controlled ◽  
Central Register ◽  
Increased Risk ◽  
All Cause Mortality

Objective To assess whether febuxostat use increases the risk of developing cardiovascular events, death from cardiac-cause and all-cause mortalities. Methods The relevant literature was searched in several databases including the MEDLINE (PubMed, 1 Jan. 1966–29 Feb. 2020), Web of science, EMBASE (1 Jan. 1974–29 Feb. 2020), ClinicalTrials.gov and Cochrane Central Register for Controlled Trials. Manual searches for references cited in the original studies and relevant review articles were also performed. All studies included in this metanalysis were published in English. Results In the end, 20 studies that met our inclusion criteria were included in this meta-analysis. Use of febuxostat was found not to be associated with an increased risk of all-cause mortality (RR = 0.87, 95% CI 0.57–1.32, P =0.507). Also, there was no association between febuxostat use and mortalities arising from cardiovascular diseases (CVD) (RR = 0.84, 95% CI 0.49–1.45, P=0.528). The RR also revealed that febuxostat use was not associated with CVD events (RR = 0.98, 95% CI 0.83–1.16, P =0.827). Furthermore, the likelihood of occurrence of CVD events was found not to be dependent on febuxostat dose (RR = 1.04, 95% CI 0.84–1.30, P =0.723). Conclusion Febuxostat use is not associated with increased risks of all-cause mortality, death from CVD or CVD events. Accordingly, it is a safe drug for the treatment of gout. Systematic review registration: PROSPERO CRD42019131872

scholarly journals Anti–PD-1 and Anti–PD-L1 in Head and Neck Cancer: A Network Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Andrea Botticelli ◽  
Alessio Cirillo ◽  
Lidia Strigari ◽  
Filippo Valentini ◽  
Bruna Cerbelli ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Head And Neck ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Head And Neck Carcinoma ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Risk Of Death ◽  
Randomized Controlled ◽  
Central Register

ObjectiveThe monoclonal antibodies anti-programmed death protein-1 (anti–PD-1) nivolumab and pembrolizumab are the first immune checkpoint inhibitors (ICIs) approved for treatment of recurrent/metastatic head and neck carcinoma R/M HNSCC in first line and in platinum refractory disease. This network meta-analysis aims to investigate the efficacy of anti–PD-1- vs anti–PD-L1-based therapy in R/M HNSCC cancer patients through a systematic review of the literature to provide support for evidence-based treatment decisions. In particular, the effectiveness of ICIs for R/M HNSCC is analyzed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.MethodsWe did a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in PubMed, ClinicalTrials.gov, Embase, Medline, the Cochrane Central Register of Controlled Trials, Web of Science. Our search identified a total of five randomized controlled trials: Keynote 040, Keynote 048, Eagle, Condor, Checkmate 141. These trials included 3001 patients. Treatment was sub-categorized into PD-L1–based, PD-1–based, and standard chemotherapy. Treatments were indirectly compared with anti–PD-L1-based therapy.ResultsThe network meta-analysis demonstrated no significant differences in OS between different subgroups except for the metastatic patients in which anti–PD-1-based therapy was associated with significantly less risk of death. Furthermore, anti–PD-1-based therapy appeared to be effective in smoker patients and in human papilloma–negative (HPV) patients. Conversely, anti–PD-L1-based therapy seems to be better efficient in female patients, in locally recurrent setting and in HPV positive patients.ConclusionThis is the first NMA study that aimed to indirectly compare anti–PD-1- and anti–PD-L1-based therapy in HNSCC patients. The results of our NMA could help define a profile of patient responder or resistant to specific classes of immune drugs and can be used to guide/design future studies in the novel scenario of precision immune-oncology.

scholarly journals Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis

2020 ◽  
Author(s):  
Joseph A. Ladapo ◽  
John E. McKinnon ◽  
Peter A. McCullough ◽  
Harvey Risch
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Side Effects ◽  
Fixed Effects ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomized Controlled ◽  
Exposure Prophylaxis

Objective--To determine if hydroxychloroquine (HCQ) reduces the incidence of new illness, hospitalization or death among outpatients at risk for or infected with SARS-CoV-2 (COVID-19). Design--Systematic review and meta-analysis of randomized clinical trials. Data sources--Search of MEDLINE, EMBASE, PubMed, medRxiv, PROSPERO, and the Cochrane Central Register of Controlled Trials. Also review of reference lists from recent meta-analyses. Study selection--Randomized clinical trials in which participants were treated with HCQ or placebo/standard-of-care for pre-exposure prophylaxis, post-exposure prophylaxis, or outpatient therapy for COVID-19. Methods--Two investigators independently extracted data on trial design and outcomes. Medication side effects and adverse reactions were also assessed. The primary outcome was COVID-19 hospitalization or death. When unavailable, new COVID-19 infection was used. We calculated random effects meta-analysis according to the method of DerSimonian and Laird. Heterogeneity between the studies was evaluated by calculation of Cochran Q and I2 parameters. An Egger funnel plot was drawn to investigate publication bias. We also calculated the fixed effects meta-analysis summary of the five studies. All calculations were done in Excel, and results were considered to be statistically significant at a two-sided threshold of P=.05. Results--Five randomized controlled clinical trials enrolling 5,577 patients were included. HCQ was associated with a 24% reduction in COVID-19 infection, hospitalization or death, P=.025 (RR, 0.76 [95% CI, 0.59 to 0.97]). No serious adverse cardiac events were reported. The most common side effects were gastrointestinal. Conclusion--Hydroxychloroquine use in outpatients reduces the incidence of the composite outcome of COVID-19 infection, hospitalization, and death. Serious adverse events were not reported and cardiac arrhythmia was rare. Systematic review registration--This review was not registered.

scholarly journals Efficacy and safety of daptomycin: systematic review and meta-analysis

2019 ◽  
Vol 6 ◽  
pp. 204993611988646
Author(s):  
María Teresa Rosanova ◽  
David Bes ◽  
Pedro Serrano-Aguilar ◽  
Norma Sberna ◽  
Estefania Herrera-Ramos ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Failure Rates ◽  
Efficacy And Safety ◽  
Fixed Effects Model ◽  
Intention To Treat ◽  
Central Register

Background: The aim of this study was to assess whether daptomycin is safer and more efficacious than comparators for the treatment of serious infection caused by gram-positive microorganisms. Methods: Electronic databases (Medline, EMBASE, the Cochrane Central Register of Controlled Trials and clinical registered trials) were searched to identify randomized controlled trials (RCTs) that assessed the efficacy and safety of daptomycin versus therapy with any other antibiotic comparator. Two reviewers independently applied selection criteria, performed a quality assessment and extracted the data. Heterogeneity was assessed, and a random-effects or fixed-effects model, when appropriate, was used for estimates of risk ratio (RR). The primary outcome assessed was the risk of clinical treatment failure among the intention-to-treat population and the presence of any treatment related adverse event (AEs). Results: A total of seven trials fulfilled the inclusion criteria. Daptomycin treatment failure rates were no different to comparator regimens (RR = 0.96; CI 95% 0.86–1.06). No significantly different treatment related AEs were identified when comparing groups (RR = 0.91; CI 95% 0.83–1.01). Conclusions: No significant differences in treatment failure rates and safety were found using daptomycin or any of the comparators treatment.

Immune-related adverse events and efficacy outcomes in patients treated with immunotherapy: A systematic review and meta-analysis.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 92-92
Author(s):  
Eric Druyts ◽  
Mark Boye ◽  
Himani Agg ◽  
Catherine Muehlenbein ◽  
Andrew Frederickson ◽  
...  
Keyword(s):  
Systematic Review ◽  
Head And Neck Cancer ◽  
Adverse Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Efficacy Data ◽  
Incidence Data ◽  
Randomized Controlled ◽  
Central Register

92 Background: Immunotherapy (IO) can lead to immune-related adverse events (irAEs). Evidence on the association of irAEs and efficacy is limited. Methods: We conducted a systematic review in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception to July 1, 2019) to identify randomized controlled trials (RCTs) reporting irAEs, incidence and efficacy data for pembrolizumab (PEM), nivolumab (NIVO), ipilimumab (IPI), atezolizumab, avelumab, durvalumab, and aldesleukin in lung, renal, head and neck cancer, and melanomas. RCTs assessing IO monotherapy or IO combinations in at least one arm were included. Evaluated outcomes were 1) irAE incidence (rash, pruritis, diarrhea, colitis, hypothyroidism, hyperthyroidism, transaminitis, hypophysitis, pneumonitis, arthralgia, anemia, and hepatitis); and 2) efficacy (response and survival). irAE incidence data will be pooled and meta-analysis performed to assess the association of irAEs with efficacy; heterogeneity between RCTs will be evaluated. Results: Fifty RCTs were included: IOs were compared to chemotherapy or chemotherapy-combinations (19), to other interventions (8), to placebo (3), and head-to-head (20). irAE reporting and definitions were heterogeneous across RCTs. The most common all-grade irAEs were skin, GI, and endocrine. For skin irAEs, rash ranged from 0% (PEM 2 mg/kg, n = 6) to 73% (NIVO + IPI, n = 11); pruritus was from 1% (PEM 2 mg/kg, n = 89) to 50% (NIVO + IPI, n = 6). For GI irAEs, diarrhea ranged from 0% (PEM 2 mg/kg, n = 6) to 64% (NIVO + IPI, n = 11); colitis was from 0% (NIVO 3 mg/kg, n = 98) to 23% (NIVO + IPI, n = 94). For endocrine irAEs, hypothyroidism ranged from 0% (NIVO 3 mg/kg, n = 12) to 83% (NIVO + IPI, n = 6), hyperthyroidism was from 0% (PEM 2 mg/kg, n = 6 and IPI 3 mg/kg, n = 46) to 27% (NIVO + IPI, n = 11), and hypophysitis was from 0% (PEM 10 mg/kg, n = 84 and NIVO 3 mg/kg, n = 25) to 26% (NIVO + IPI, n = 35). Liver, pulmonary, and musculoskeletal irAEs, and anemia, were reported less frequently and with lower incidence. Conclusions: irAEs are increasingly reported in IO RCTs, but lack reporting and definition consistency. The meta-analysis results may provide clarity on irAEs incidence and association with efficacy.

scholarly journals Effect of Berry Polyphenols on Glucose Metabolism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Theresa F Rambaran ◽  
Jonathan Bergman ◽  
Peter Nordström ◽  
Anna Nordström
Keyword(s):  
Systematic Review ◽  
Glucose Metabolism ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomized Controlled ◽  
Inverse Variance ◽  
Central Register ◽  
Mean Differences

ABSTRACT The effect of berry polyphenols on glucose metabolism has been evaluated in several studies; however, the results are conflicting. A systematic review and meta-analysis was therefore conducted to evaluate the effect of berry polyphenol consumption on glucose metabolism in adults with impaired glucose tolerance or insulin resistance. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, CINAHL (EBSCO), and Scopus were searched for randomized controlled trials published by June 2019. Of the 3240 articles found, 21 met inclusion criteria. Study-specific effects were calculated as mean differences, which were pooled using fixed-effect, inverse-variance weighting. Overall, berry polyphenol consumption did not have a clear effect on biomarkers of glucose metabolism compared with placebo or no treatment. Although some analyses showed statistically significant effects, these effects were too small to be of clinical relevance. The review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews as CRD42019130811.

scholarly journals The Effects of Exercise on BDNF Levels in Adolescents: A Systematic Review with Meta-Analysis

2020 ◽  
Vol 17 (17) ◽  
pp. 6056
Author(s):  
Kesley Pablo Morais de Azevedo ◽  
Victor Hugo de Oliveira ◽  
Gidyenne Christine Bandeira Silva de Medeiros ◽  
Ádala Nayana de Sousa Mata ◽  
Daniel Ángel García ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Control Group ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Exercise Programs ◽  
Randomized Controlled ◽  
Central Register ◽  
Before And After

The aim of this study was to analyze the evidence available in the literature about the effects of exercise on brain-derived neurotrophic factor levels in adolescents. The literature searches were conducted in PubMed, Embase, Scopus, ScienceDirect, Web of Science, SportDiscus, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL. Randomized controlled trials and non-randomized controlled trials performed with adolescents (10–19 years) who underwent different exercise programs and who evaluated BDNF levels before and after the intervention were included. We included six studies, four RCTs and two non-RCTs in the systematic review with a total of 407 adolescents. In two randomized trials and one non-RCT, the intervention groups showed significant improvements in BDNF levels compared with the control group. The results presented in the meta-analysis indicate that despite the positive effect in favor of the intervention, there were no significant differences (standardized mean difference 0.28 ng/mL, 95% confidence interval −0.28 to 0.85; p = 0.32, I² = 0%). The results presented in our review indicate that aerobic exercise programs practiced in moderate- or high-intensity are promising strategies to increase BDNF levels in adolescents. However, further studies are required to support this finding.

scholarly journals Effect of diuretics on plasma aldosterone and potassium in primary hypertension: A systematic review and meta-analysis

2021 ◽  
Author(s):  
Ryan McNally ◽  
Bushra Farukh ◽  
P J Chowienczyk ◽  
Luca Faconti
Keyword(s):  
Systematic Review ◽  
Antihypertensive Medication ◽  
Meta Analysis ◽  
Diuretic Therapy ◽  
Plasma Aldosterone ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Exclusion Criteria ◽  
Randomized Controlled ◽  
Central Register

Aim: Different to inhibitory drugs of the renin-angiotensin-aldosterone system (RAAS), diuretics are known to decrease blood pressure (BP) and stimulate renin release by the kidneys. Despite plasma aldosterone (PA) level is mostly regulated by the RAAS activity, serum potassium has been shown to be an important factor in animal models and humans. Here we perform a systematic review and meta-analysis of randomized-controlled trials investigating the effects of diuretic therapy on PA and its correlation with change in potassium and BP. Methods: Three databases were searched: MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials (CENTRAL). Titles were firstly screened by title and abstract for relevancy before full-text articles were assessed for eligibility according to a pre-defined inclusion/exclusion criteria. Results: A total of 1139 articles were retrieved of which 45 met the pre-specified inclusion/exclusion criteria. The average standardised difference in mean PA change was similar for all classes of diuretic (mean, 95% CI); thiazide/thiazide-like 0.304 (0.169, 0.440), loop 0.927 (0.37, 1.49), MRA/potassium-sparing 0.264 (0.174, 0.355) and combination 0.466 (0.142, 0.789), Q = 6.475, P = 0.091. In subjects previously untreated with another antihypertensive, there was a significant relationship between PA change and change in systolic BP but no relationship with the change in potassium. Conclusion: In RCTs of diuretic therapy in hypertension, there is an increase in PA with all classes of diuretic and no between-class heterogeneity. Change in PA is not related with potassium but correlates to the change in BP in subjects previously untreated with another antihypertensive medication.

scholarly journals Efficacy and Safety of Atropine to Control Myopia Progression: a Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Congling Zhao ◽  
Chunyan Cai ◽  
Qiang Ding ◽  
Hongbin Dai
Keyword(s):  
Meta Analysis ◽  
Optimal Dose ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Myopia Progression ◽  
Randomized Controlled ◽  
Central Register ◽  
Atropine Treatment ◽  
Dose Dependent

Abstract Purpose: To systematically evaluate the safety and effectiveness of atropine in controlling the progression of myopia.Methods: This work was done through the data search from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The Cochrane Handbook was also used to evaluate the quality of these included studies. In addition, a meta-analysis was performed using Revman5.3 software.Results: A total of 10 randomized controlled trials (RCTs) were included. Myopia progression was mitigated in the atropine treatment group, with MD = -0.80, 95% CI (-0.94, -0.66). There was a statistical difference between 0.05%, 0.5%, and 1.0% atropine (P = 0.004). In addition, axial elongation was slowed, with MD = -0.26, 95% CI (-0.33, -0.18).Conclusion: The effect of atropine in controlling the progression of myopia was dose-dependent. A 0.05% atropine was most likely to be the optimal dose.

Novel chemotherapy combinations for metastatic gastric adenocarcinoma (mAGC): An updated meta-analysis.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 125-125 ◽  
Author(s):  
Anna Dorothea Wagner ◽  
Markus Moehler ◽  
Wilfried Grothe ◽  
Johannes Haerting ◽  
Susanne Unverzagt
Keyword(s):  
Overall Survival ◽  
Selection Criteria ◽  
Meta Analysis ◽  
Treatment Options ◽  
Single Agent ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Central Register ◽  
Randomised Controlled ◽  
Meta Analyses

125 Background: Despite the successful integration of targeted therapies, chemotherapy remains the mainstay of treatment for mAGC. Uncertainty remains regarding the choice of the regimen. Methods: We searched: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE until February 2014; proceedings from ECCO, ESMO, ASCO until June 2014 with Selection criteria: Randomised controlled trials on chemotherapy in mAGC. Objectives: To assess and compare the effects on overall survival of regimens containing: 1) irinotecan (I) vs non-I, 2) docetaxel (D) vs non-D, 3) capecitabine (C) vs 5-FU, 4) S-1 vs 5-FU, 5) oxaliplatin (O) vs the same regimen containing cisplatin. For 1) and 2), substitutive (other chemotherapy substituted by I or D) and additive comparisons (I or D added) were analyzed separately. Results: The meta-analyses of overall survival included: Comparison 1) a. Substitutive: 5 trials, 724 patients (pts), with a HR of 0.85 (95% CI 0.73-0.99), b. Additive: 3 trials, 500 pts, with a HR of 0.88 (95% CI 0.76-1.03), both in favor of the I-containing regimens. Comparison 2) In total, 6 trials, 1702 pts, with a HR of 0.89 (95% CI 0.80-0.99) in favor of patients treated with D. a. Substitutive: 3 trials, 479 pts, with a HR of 1.05 (95% CI 0.87-1.27) in favor of patients treated without D. b. Additive: 3 trials, 1223 pts, with a HR of 0.82 (95% CI 0.87-0.93), in favor of D-containing regimens. If only studies (2 trials, 588 pts) are considered, in which D is added to a platinum/5-FU doublet, the HR is 0.79 (95% CI 0.64-0.98) in favor of the D-containing regimen. Comparison 3) 2 trials, 401 pts, with a HR of 0.85 (95% CI 0.68-1.06) in favor of the C-containing-regimen. Comparison 4) 2 trials, 1497 pts, with a HR of 0.89 (95% CI 0.80-1.0) in favor of the S-1-containing regimen. Comparison 5) 1 trial, 220 pts, with a HR of 0.82 (0.47-1.45) in favor of the O-containing regimen. Conclusions: All different chemotherapy combinations including I, D, O or oral 5-FU prodrugs are valid treatment options for mAGC. Among the comparisons analyzed above, only D-containing combinations, in which D was added to a single-agent or two-drug (platinum/5-FU) combination show a significant advantage in overall survival as compared to regimens without D.

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