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1.
Pharmacol Res ; 157: 104872, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318931

ABSTRACT

The rapidly progressing of coronavirus disease 2019 (COVID-19) pandemic has become a global concern. This meta-analysis aimed at evaluating the efficacy and safety of current option of therapies for severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS) besides COVID-19, in an attempt to identify promising therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. We searched PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WANFANG DATA for randomized controlled trials (RCTs), prospective cohort, and retrospective cohort studies that evaluated therapies (hydroxychloroquine, lopinavir/ritonavir-based therapy, and ribavirin-based therapy, etc.) for SARS, MERS, and COVID-19. The primary outcomes were mortality, virological eradication and clinical improvement, and secondary outcomes were improvement of symptoms and chest radiography results, incidence of acute respiratory disease syndrome (ARDS), utilization of mechanical ventilation, and adverse events (AEs). Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was appraised using GRADEpro. Eighteen articles (5 RCTs, 2 prospective cohort studies, and 11 retrospective cohort studies) involving 4,941 patients were included. Compared with control treatment, anti-coronary virus interventions significantly reduced mortality (RR 0.65, 95% CI 0.44-0.96; I2 = 81.3%), remarkably ameliorate clinical improvement (RR 1.52, 95% CI 1.05-2.19) and radiographical improvement (RR 1.62, 95% CI 1.11-2.36, I2 = 11.0 %), without manifesting clear effect on virological eradication, incidence of ARDS, intubation, and AEs. Subgroup analyses demonstrated that the combination of ribavirin and corticosteroids remarkably decreased mortality (RR 0.43, 95% CI 0.27-0.68). The lopinavir/ritonavir-based combination showed superior virological eradication and radiographical improvement with reduced rate of ARDS. Likewise, hydroxychloroquine improved radiographical result. For safety, ribavirin could induce more bradycardia, anemia and transaminitis. Meanwhile, hydroxychloroquine could increase AEs rate especially diarrhea. Overall, the quality of evidence on most outcomes were very low. In conclusion, although we could not draw a clear conclusion for the recommendation of potential therapies for COVID-19 considering the very low quality of evidence and wide heterogeneity of interventions and indications, our results may help clinicians to comprehensively understand the advantages and drawbacks of each anti-coronavirus agents on efficacy and safety profiles. Lopinavir/ritonavir combinations might observe better virological eradication capability than other anti-coronavirus agents. Conversely, ribavirin might cause more safety concerns especially bradycardia. Thus, large RCTs objectively assessing the efficacy of antiviral therapies for SARS-CoV-2 infections should be conducted with high priority.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Antiviral Agents/adverse effects , Betacoronavirus/drug effects , COVID-19 , Humans , Pandemics , SARS-CoV-2
2.
CNS Spectr ; 26(2): 164, 2021 04.
Article in English | MEDLINE | ID: covidwho-1228225

ABSTRACT

BACKGROUND: Deutetrabenazine is approved to treat tardive dyskinesia (TD) in adults and is titrated weekly by 6 mg/day, from 12 to 48 mg/day, based on dyskinesia control and tolerability. This analysis compared the safety of deutetrabenazine during titration versus maintenance. METHODS: Safety was assessed during titration versus maintenance using integrated data from two 12-week placebo-controlled studies (ARM-TD and AIM-TD) and the open-label extension study. Rates were compared for overall and serious adverse events (AEs), AEs leading to discontinuation, treatment-related AEs, common AEs (≥4%), and specific AEs (parkinsonism, suicidal ideation, akathisia, restlessness). RESULTS: In titration versus maintenance, AE rates with placebo (n=130) were: overall, 43.1% vs 25.4%; serious, 4.6% vs 2.3%; leading to discontinuation, 3.1% vs 0; treatment-related, 26.9% vs 10.0%. For placebo, common AEs during titration were somnolence, headache, nausea, fatigue, and dry mouth; none occurred during maintenance. In titration versus maintenance, AE rates in fixed-dose deutetrabenazine 12-36 mg (n=216) were: overall, 33.3-38.9% vs 22.2-29.2%; serious, 2.8-6.9% vs 0-1.4%; leading to discontinuation, 2.8-5.6% vs 0; treatment-related, 8.3-16.7% vs 8.3-13.9%. For fixed-dose deutetrabenazine, common AEs during titration were headache, diarrhea, nasopharyngitis, depression, hypertension, and dry mouth; headache was the only common AE during maintenance. In titration versus maintenance, AE rates with flexible-dose deutetrabenazine (n=168) were: overall, 49.4% vs 32.7%; serious, 3.6% vs 2.4%; leading to discontinuation, 2.4% vs 0.6%. For flexible-dose deutetrabenazine, the only common AE during titration was somnolence; none occurred during maintenance. Rates of parkinsonism, suicidal ideation, akathisia, and restlessness were low and comparable in titration and maintenance. CONCLUSIONS: Deutetrabenazine was well-tolerated, with AE rates similar to placebo during both phases; AE rates were higher during titration and decreased during maintenance. FUNDING: Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.


Subject(s)
Tardive Dyskinesia/drug therapy , Tetrabenazine/analogs & derivatives , Humans , Tetrabenazine/adverse effects , Tetrabenazine/therapeutic use
3.
J Public Health Res ; 10(1): 1945, 2021 Jan 14.
Article in English | MEDLINE | ID: covidwho-1097334

ABSTRACT

To date, there is no definite effective treatment for the COVID- 19 pandemic. We performed an update network meta-analysis to compare and rank COVID-19 treatments according to their efficacy and safety. Literature search was performed from MEDLINE and CENTRAL databases from inception to September 5, 2020. Randomized clinical trials (RCTs) which compared the effect of any pharmacological drugs versus standard care or placebo 28-day after hospitalization in adult patients with COVID-19 disease were included. Risk ratio (RR) and 95% CI were calculated for 28-day all-cause mortality, clinical improvement, any adverse event (AEs), and viral clearance. A total of 25 RCTs, evaluating 17 different treatments, and 11,597 participants were analyzed. Remdesivir for 10- day compared to standard care (RR 0.69, 95% CI [0.48-0.99]), and a low dose compared to a high dose of HCQ (0.38, [0.17-0.89]) were associated with a lower risk of death. A total of 2,766 patients experienced clinical improvement, a 5-day course of remdesivir was associated with a higher frequency of clinical improvement compared to standard care (RR 1.21, 95% CI [1.00-1.47]). Compared to standard care, remdesivir for both 5 and 10 days, lopinavir/ritonavir, and dexamethasone reduced the risk of any severe AEs by 52% (0.48, 0.34-0.67), 24% (0.77, 0.63-0.92), 40% (0.60, 0.37-0.98), and 50% (0.50, 0.25-0.98) respectively. In this study of hospitalized patients with COVID-19, administration of remdesivir for 10-day compared to standard care was associated with lower 28-day all-cause mortality and serious AEs, and higher clinical improvement rate.

4.
Front Pharmacol ; 11: 562777, 2020.
Article in English | MEDLINE | ID: covidwho-904744

ABSTRACT

BACKGROUND: Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have recently 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). METHODS: We systematically searched MEDLINE, the Cochrane library, the Cochrane Central Register of Controlled Trials (CENTRAL), and the ClinicalTrials.gov for all the RCTs comparing CQ or HCQ with placebo or other active agents, published before June 20, 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. RESULTS: The literature search yielded 23 and 19 studies for CQ and HCQ, respectively, that satisfied our inclusion criteria. Of these studies, we performed meta-analysis on 6 studies for CQ and 18 studies for HCQ. We did not limit our analysis to published records 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 2,675 participants (n = 1,345 HCQ and n = 1,330 control). The overall mild and total AEs were significantly higher in CQ-treated non-COVID-19 patients, HCQ-treated non-COVID-19 patients, and HCQ-treated COVID-19 patients. The AEs were further categorized into four groups and analyses revealed that neurologic, gastrointestinal (GI), dermatologic, and sensory AEs were higher in participants taking CQ compared to placebo, while GI, dermatologic, sensory, and cardiovascular AEs were higher in HCQ-treated COVID-19 patients compared to control patients. Moreover, subgroup analysis suggested higher AEs with respect to dosage and duration in HCQ group. Data were acquired from studies with perceived low risk of bias, so plausible bias is unlikely to seriously affect the main findings of the current study. CONCLUSIONS: Taken together, we found that participants taking either CQ or HCQ exhibited more AEs than participants taking placebo or control. Precautionary measures should be taken when using these drugs to treat COVID-19. The meta-analysis was registered on OSF (https://osf.io/jm3d9). REGISTRATION: The meta-analysis was registered on OSF (https://osf.io/jm3d9).

5.
Eur J Clin Pharmacol ; 77(1): 13-24, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-710271

ABSTRACT

INTRODUCTION: Many concerns still exist regarding the safety of hydroxychloroquine (HCQ) in the treatment of Coronavirus Disease 2019 (COVID-19). OBJECTIVES: The purpose of this study was to evaluate the safety of HCQ in the treatment of COVID-19 and other diseases by performing a systematic review and meta-analysis. METHODS: Randomized controlled trials (RCTs) reporting the safety of HCQ in PubMed, Embase, and Cochrane Library were retrieved starting from the establishment of the database till June 5, 2020. Literature screening, data extraction, and assessment of risk bias were performed independently by two reviewers. RESULTS: We identified 53 eligible studies involving 5496 patients. The meta-analysis indicated that the risk of adverse effects (AEs) in the HCQ group was significantly increased compared with that in the control group (RD 0.05, 95%CI, 0.02 to 0.07, P = 0.0002), and the difference was also statistically significant in the COVID-19 subgroup (RD 0.15, 95%CI, 0.07 to 0.23, P = 0.0002) as well as in the subgroup for other diseases (RD 0.03, 95%CI, 0.01 to 0.04, P = 0.003). CONCLUSIONS: HCQ is associated with a high total risk of AEs compared with the placebo or no intervention in the overall population. Given the small number of COVID-19 participants included, we should be cautious regarding the conclusion stating that HCQ is linked with an increase incidence of AEs in patients with COVID-19, which we hope to confirm in the future through well-designed and larger sample size studies.


Subject(s)
COVID-19/drug therapy , Hydroxychloroquine/adverse effects , SARS-CoV-2 , Cardiotoxicity/etiology , Gastrointestinal Tract/drug effects , Humans , Outcome Assessment, Health Care , Publication Bias , Skin/drug effects
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