scholarly journals Low dose hydroxychloroquine is associated with lower mortality in COVID-19: a meta-analysis of 26 studies and 44,521 patients

2020 ◽  
Author(s):  
Augusto Di Castelnuovo ◽  
Simona Costanzo ◽  
Antonio Cassone ◽  
Roberto Cauda ◽  
Giovanni de Gaetano ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Risk Ratio ◽  
Mortality Risk ◽  
Observational Studies ◽  
Low Dose ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Total Mortality ◽  
Lower Mortality ◽  
Lower Mortality Risk

ABSTRACTBackgroundHydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19, but its association with mortality is not well characterized. We conducted two meta-analyses to evaluate the association between HCQ (with or without azithromycin (AZM)) and total mortality in COVID-19 patients.MethodsArticles were retrieved until October 20th, 2020 by searching in seven databases. Data were combined using the general variance-based method on relative risk estimates.ResultsA total of 26 articles were found (N=44,521 COVID-19 patients, including N=7,324 from 4 randomized clinical trials (RCTs)); 10 studies were valuable for analysing the association of HCQ+AZM. Overall, the use of HCQ was associated with 21% lower mortality risk (pooled risk ratio: 0.79, 95%CI: 0.67 to 0.93; high level of heterogeneity: I2=82%, random effects). This association vanished (1.10, 95%CI: 0.99 to 1.23 and 1.10, 95%CI: 0.99 to 1.23) when daily dose >400 mg or total dose >4,400 mg were used, respectively). HCQ+AZM was also associated with 25% lower mortality risk, but uncertainty was large (95%CI: 0.50 to 1.13; P=0.17). No association was apparent when only pooling the 4 RCTs (13.8% of the overall weight; pooled risk ratio: 1.11, 95%CI: 0.99 to 1.24).ConclusionsHCQ use was not associated with either increased or decreased mortality in COVID-19 patients when 4 RCTs only were evaluated, while a 7% to 33% reduced mortality was observed when observational studies were also included. The association was mainly apparent when pooling studies using lower doses of HCQ. These findings can help disentangling the debate on HCQ use in COVID-19.Key-pointsLow dose hydroxychloroquine was associated with reduced mortality in COVID-19 patients, as seen in observational studies but not in randomised clinical trials, which used high doses of hydroxychloroquine. These findings can help disentangling the debate on hydroxychloroquine use in COVID-19.

scholarly journals Low Dose Hydroxychloroquine is Associated with Lower Mortality in COVID-19: A Meta-Analysis of 27 Studies and 44,684 Patients

2020 ◽  
Author(s):  
Augusto Di Castelnuovo ◽  
Simona Costanzo ◽  
Antonio Cassone ◽  
Roberto Cauda ◽  
Giovanni de Gaetano ◽  
...  
Keyword(s):  
Risk Ratio ◽  
Mortality Risk ◽  
Low Dose ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Total Mortality ◽  
Lower Mortality ◽  
Daily Dose ◽  
Meta Analyses ◽  
Lower Mortality Risk

Abstract Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19, but its association with mortality is not well characterized. We conducted two meta-analyses to evaluate the association between HCQ (with or without azithromycin (AZM)) and total mortality in COVID-19 patients.Methods: Articles were retrieved until November 10th, 2020 by searching in seven databases. Data were combined using the general variance-based method.Results: A total of 27 articles were found (N=44,684 patients, including N=7,803 from 5 randomized clinical trials (RCTs)). Overall, the use of HCQ was associated with 22% lower mortality risk (pooled risk ratio: 0.78, 95%CI: 0.67 to 0.91; I2=80%, random effects). This association was found reversed when pooling only RCTs (16.7% of the overall weight; pooled risk ratio: 1.11, 0.99 to 1.24) or studies in which daily dose >400 mg or total dose >4,400 mg were used (pooled risk ratio: 1.10, 95%CI: 0.99 to 1.23 in both cases). Overall, HCQ+AZM (10 studies) was also associated with 28% lower mortality risk, but uncertainty was large (95%CI: 0.48 to 1.08; P=0.11). Use of HCQ was not associated with severe adverse events.Conclusions: HCQ use was not associated with mortality reduction in COVID-19 patients when 5 RCTs only were evaluated, while a 9% to 33% reduced mortality was observed when observational studies were also included. The association was mainly apparent in studies that used lower doses of HCQ. These findings can help disentangling the debate on HCQ use in COVID-19.

scholarly journals Suicidality: Once Again, Don’t Blame the Drug Class

2021 ◽  
pp. 153575972110531
Author(s):  
Faught Edward
Keyword(s):  
Clinical Trials ◽  
Suicidal Ideation ◽  
Risk Ratio ◽  
Randomized Clinical Trials ◽  
Rating Scale ◽  
Meta Analysis ◽  
Adjunctive Treatment ◽  
Current Evidence ◽  
Phase 2 ◽  
Increased Risk

Importance Mostantiseizure medications (ASMs) carry a US Food and Drug Administration–mandated class label warning of increased suicidality risk, based on a meta-analysis comparing suicidality between individuals treated with medications vs placebo in randomized clinical trials done before 2008. ASMs approved since then carry this warning although they were not similarly studied. Objective To review all placebo-controlled phase 2 and 3 studies of 10 ASMs approved since 2008 to evaluate the risk of suicidality of these drugs compared with placebo. Data Sources Primary publications and secondary safety analyses in PubMed of all phase 2 and 3 randomized placebo-controlled epilepsy trials of ASMs approved since 2008, using keywords epilepsy, antiepileptic drugs, seizures, suicidality, suicidal ideation, and the names of individual drugs. Study Selection All phase 2 and 3 randomized clinical trials of adjunctive treatment of drug-resistant epilepsy and their secondary safety analyses. Data Extraction and Synthesis Articles were reviewed for frequency of suicidality (ideation, attempts, and completed suicides). Mode of suicidality ascertainment included treatment-emergent adverse event reports, Standardized Medical Dictionary for Regulatory Activities queries for events in prespecified categories including suicidal ideation and behavior, prospective collection of suicidality data as a prespecified safety outcome using the Columbia-Suicide Severity Rating Scale, and retrospective evaluation by blinded review using the Columbia-Classification Algorithm of Suicide Assessment. A meta-analysis compared risk for drugs vs placebo of each outcome for all drugs overall and by individual drugs and trials. Main Outcomes and Measures Suicidality (total and by ideation), attempts, and completed suicides. Results Excluding studies that did not evaluate suicidality (everolimus and fenfluramine) or did not evaluate it prospectively (lacosamide, ezogabine, and clobazam), 5 drugs were analyzed: eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. Suicidality was evaluated in 17 randomized clinical trials of these drugs, involving 5996 patients, of whom 4000 patients were treated with ASMs and 1996 with placebo. There was no evidence of increased risk of suicidal ideation (drugs vs placebo overall risk ratio, .75; 95% CI, .35–1.60) or attempt (risk ratio, .75; 95% CI, .30–1.87) overall or for any individual drug. Suicidal ideation occurred in 12 of 4000 patients treated with ASMs (.30%) vs 7 of 1996 patients treated with placebo (.35%) ( P  =  .74). Three patients treated with ASMs and no patients treated with placebo attempted suicide ( P  =  .22). There were no completed suicides. Conclusions and Relevance There is no current evidence that the 5 ASMs evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning

scholarly journals Efficacy of Low-Dose Paroxetine for the Treatment of Hot Flushes in Surgical and Physiological Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Trials

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 554
Author(s):  
Gaetano Riemma ◽  
Antonio Schiattarella ◽  
Marco La Verde ◽  
Giuseppina Zarobbi ◽  
Simone Garzon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Postmenopausal Women ◽  
Sleep Disturbances ◽  
Low Dose ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Hormonal Treatment ◽  
Significant Heterogeneity ◽  
Hot Flushes ◽  
Night Time

Background and Objectives: Hot flushes and sleep disturbances are the most common vasomotor symptoms (VMS) reported by postmenopausal women. Hormonal treatment is to date referred to as the gold standard approach but not suitable for all the patients. Alternative treatments are needed in case of a contraindication to menopausal hormone therapy (MHT), adverse side effects, and poor compliance. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS. Nonetheless, few trials with low consensus are available about this topic. In this review, we aimed to evaluate the efficacy of low-dose paroxetine therapy in the treatment of vasomotor hot flushes and night sleep disturbances in postmenopausal women. Materials and Methods: We performed an electronic search from the beginning of all databases to July 2019. All results were then limited to a randomized trial. Restrictions for language or geographic location were not utilized. Inclusion criteria were randomized clinical trials of physiological or surgical postmenopausal women experiencing hot flushes and sleep disturbances who were randomized to either low-dose paroxetine or placebo (i.e., formulations without active ingredients). The primary outcome evaluated was the mean weekly reduction of hot flushes. Results: Five randomized clinical trials, including 1482 postmenopausal women, were analyzed. Significant heterogeneity (I2 = 90%) between studies was noted. Hot flushes episodes were significantly reduced in the treatment arm compared to placebo (mean difference (MD) −7.97 [−10.51, −5.92] episodes/week). Results on the improvement on sleep were limited by being reported in only two studies; however, no significant reduction of night-time awakenings was observed (MD, −0.40 awakenings/night [−1.38, 0.58 CI]). Conclusions: Low-dose paroxetine is an effective treatment for vasomotor menopause symptoms, including hot flushes.

scholarly journals Low-Dose Acetylsalicylic Acid Use and the Risk of Upper Gastrointestinal Bleeding: A Meta-Analysis of Randomized Clinical Trials and Observational Studies

2013 ◽  
Vol 27 (3) ◽  
pp. 159-167 ◽  
Author(s):  
Vera E Valkhoff ◽  
Miriam CJM Sturkenboom ◽  
Catherine Hill ◽  
Sander Veldhuyzen van Zanten ◽  
Ernst J Kuipers
Keyword(s):  
Gastrointestinal Bleeding ◽  
Acetylsalicylic Acid ◽  
Observational Studies ◽  
Low Dose ◽  
Randomized Clinical Trials ◽  
Upper Gastrointestinal Bleeding ◽  
Meta Analysis ◽  
Case Control Studies ◽  
Increased Risk ◽  
Upper Gastrointestinal

BACKGROUND: Low-dose acetylsalicylic acid (LDA, 75 mg/day to 325 mg/day) is recommended for primary and secondary prevention of cardiovascular events, but has been linked to an increased risk of upper gastrointestinal bleeding (UGIB).OBJECTIVE: To analyze the magnitude of effect of LDA use on UGIB risk.METHODS: The PubMed and Embase databases were searched for randomized controlled trials (RCTs) reporting UGIB rates in individuals receiving LDA, and observational studies of LDA use in patients with UGIB. Studies were pooled for analysis of UGIB rates.RESULTS: Eighteen studies were included. Seven RCTs reported UGIB rates in individuals randomly assigned to receive LDA (n=22,901) or placebo (n=22,923). Ten case-control studies analyzed LDA use in patients with UGIB (n=10,816) and controls without UGIB (n=30,519); one cohort study reported 207 UGIB cases treated with LDA only. All studies found LDA use to be associated with an increased risk of UGIB. The mean number of extra UGIB cases associated with LDA use in the RCTs was 1.2 per 1000 patients per year (95% CI 0.7 to 1.8). The number needed to harm was 816 (95% CI 560 to 1500) for RCTs and 819 (95% CI 617 to 1119) for observational studies. Meta-analysis of RCT data showed that LDA use was associated with a 50% increase in UGIB risk (OR 1.5 [95% CI 1.2 to 1.8]). UGIB risk was most pronounced in observational studies (OR 3.1 [95% CI 2.5 to 3.7]).CONCLUSIONS: LDA use was associated with an increased risk of UGIB.

scholarly journals The efficacy and safety of bamlanivimab treatment against COVID-19: A meta-analysis

2021 ◽  
Author(s):  
Huairong Xiang ◽  
Bei He ◽  
Yun Li ◽  
Xuan Cheng ◽  
Qizhi Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Observational Studies ◽  
Randomized Clinical Trials ◽  
Web Of Science ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Positive Treatment ◽  
The Cochrane Library

Background: Bamlanivimab is routinely used in the treatment of coronavirus disease 2019 (COVID-19) in worldwide. We performed a meta-analysis to investigate the efficacy and safety of bamlanivimab treatment in patients with COVID-19. Methods: We searched articles from Web of Science, PubMed, Embase, the Cochrane Library and MedRxiv between 30 January 2020 and August 5, 2021. We selected randomized clinical trials (RCTs) and observational studies with a control group to assess the efficiency of bamlanivimab in treating patients with COVID-19. Results: Our meta-analysis retrieved 3 RCTs and 7 cohort studies including 14461 patients. Bmlanivimab may help outpatients to prevent hospitalization or emergency department visit (RR 0.41 95%CI 0.29 to 0.58), reduce ICU admission (RR 0.47 95%CI 0.23 to 0.92) and mortality (RR 0.32 95%CI 0.13 to 0.77) from the disease. The combination of bamlanivimab and etesevimab may had a greater potential for positive treatment outcome. Conclusion: Bamlanivimab has demonstrated clinical efficacy on mild or moderate ill patients with COVID-19 to prevent hospitalization, reduce severity and mortality from the disease. Combinations of two or more monoclonal antibody increase the effect. Well-designed clinical trials to identify the clinical and biochemical characteristics in COVID-19 patients'population that could benefit from bamlanivimab are warranted in the future.

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