scholarly journals Three-Drug Regimens Containing Integrase Inhibitor Show Good Efficacy and Safety in Treatment-Naive Patients With HIV-1: A Bayesian Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ke Zhang ◽  
Yang Zhang ◽  
Xinchao Liu ◽  
Aixin Li ◽  
Meixia Gao ◽  
...  
Keyword(s):  
Adverse Events ◽  
Meta Analysis ◽  
Integrase Inhibitor ◽  
Controlled Trials ◽  
Virologic Suppression ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Treatment Naïve ◽  
Drug Regimens ◽  
Hiv 1

Introduction: The extensive utilisation of antiretroviral therapy has greatly improved the survival rates of those infected with human immunodeficiency virus (HIV). The objective of this study was to compare 3-drug regimens containing non-nucleoside reverse transcriptase inhibitor with 3-drug regimens containing integrase inhibitor (INI) regarding efficacy and safety in treatment-naive HIV-1-infected adults at 48 and 96 weeks, respectively.Methods: This study was a network meta-analysis using a Bayesian methodology. On January 8, 2020, we searched databases and other sources for randomized controlled trials conducted in treatment-naive HIV-1 adults and compared multiple 3-drug antiretroviral regimens containing INI, efavirenz (EFV), or rilpivirine (RPV). We extracted data on the following outcomes: virologic suppression, CD4+ cell recovery, discontinuations, deaths, adverse events, serious adverse events, deaths related to study drugs, and drug-related adverse events. We conducted calculations within a Bayesian framework using R software.Results: The network contained 15 randomized controlled trials including 9,745 patients. For efficacy outcomes, regimens containing INI, especially dolutegravir (DTG), were generally superior to other regimens. For virologic suppression at 48 weeks, odds ratios (95% credible intervals) were 0.6 (0.43, 0.82) for EFV+ tenofovir disoproxil fumarate (TDF)+emtricitabine (FTC) versus DTG+ abacavir+ lamivudine (3TC) and 0.52 (0.36, 0.75) for EFV+TDF+FTC vs. DTG+TDF+FTC/3TC. For safety outcomes, regimens containing INI tended to be safer relative to regimens without INI. Outcomes associated with death were unsuitable for network meta-analysis due to low event rates.Conclusion: 3-drug regimens containing INI demonstrate better efficacy and safety than those containing RPV or EFV.

Inhaled Levodopa (CVT-301) for the Treatment of Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

2021 ◽  
pp. 10.1212/CPJ.0000000000001143
Author(s):  
Glenardi Glenardi ◽  
Tutwuri Handayani ◽  
Jimmy Barus ◽  
Ghea Mangkuliguna
Keyword(s):  
Systematic Review ◽  
Placebo Group ◽  
Adverse Events ◽  
Respiratory Symptoms ◽  
Meta Analysis ◽  
Motor Fluctuation ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Improve Motor Function

ABSTRACTPurposeof Review: To investigate the efficacy and safety of CVT-301 for motor fluctuation in Parkinson’s disease (PD).Recent Findings:This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (OR=2.68; 95% CI: 1.86-3.86; p<0.00001). Moreover, CVT-301 had also shown to improve motor function by UPDRS-III score (SMD=3.83; 95% CI: 2.44-5.23; p<0.00001) and promote an overall improvement of PD by PGIC self-rating (OR=2.95; 95% CI: 1.78-4.9; p<0.00001). The most common adverse events encountered were respiratory symptoms (OR=12.18; 95% CI: 5.01-29.62; p<0.00001) and nausea (OR=3.95; 95% CI: 1.01-15.41; p=0.05).Summary:CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in PD patients.

Efficacy and safety of bempedoic acid in patients with hypercholesterolemia: A systematic review and meta-analysis of randomized controlled trials

2020 ◽  
pp. 204748732093058 ◽  
Author(s):  
Lei Dai ◽  
Yuyue Zuo ◽  
Qiqi You ◽  
Hesong Zeng ◽  
Shiyi Cao
Keyword(s):  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Fixed Effects ◽  
Therapeutic Option ◽  
Meta Analysis ◽  
Lipid Lowering ◽  
Oral Drug ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled

Aim Bempedoic acid is a novel oral drug, which has been increasingly researched to play an important role in the treatment of hypercholesterolemia recently. However, results from original studies were inconsistent and inconclusive. We aimed to conduct a meta-analysis to quantitatively appraise the efficacy and safety of bempedoic acid. Methods PubMed, Embase, Web of Science and Scopus were searched from inception to 30 January 2020. We included randomized controlled trials that compared the efficacy and safety of bempedoic acid with placebo in patients with hypercholesterolemia. Results from trials were presented as mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled by random or fixed effects model. The risk of bias and heterogeneity among trials were also assessed and analyzed. Results Pooled analysis of 10 eligible trials showed that bempedoic acid treatment resulted in greater lowering of the low-density lipoprotein cholesterol level than the placebo group (mean difference –23.16%, 95% CI –26.92% to –19.04%). We also found that improvements in lipid parameters and biomarkers were still maintained at weeks 24 and 52 from the long-term trials. As for safety, bempedoic acid did not increase the risk of overall adverse events (OR 1.02, 95% CI 0.88 to 1.18). However, the incidence of adverse events leading to discontinuation was higher in the bempedoic acid group (OR 1.44, 95% CI 1.14 to 1.82). Conclusions Available evidence from randomized controlled trials suggests that bempedoic acid provides a well-tolerated and effective therapeutic option for lipid lowering in patients with hyperlipidemia

scholarly journals Pridopidine for the Improvement of Motor Function in Patients With Huntington's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Shujun Chen ◽  
Tianyu Liang ◽  
Tao Xue ◽  
Shouru Xue ◽  
Qun Xue
Keyword(s):  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Motor Score ◽  
Randomized Controlled

Background: Huntington's disease (HD) is a progressive neurodegenerative disorder. Generally, it is characterized by deficits in cognition, behavior, and movement. Recent studies have shown that pridopidine is a potential and effective drug candidate for the treatment of HD. In the present study, we performed a meta-analysis to evaluate the efficacy and safety of pridopidine in HD.Methods: The MEDLINE, EMBASE, CENTRAL, and Clinicaltrials.gov databases were searched for randomized controlled trials (RCTs) which had that evaluated pridopidine therapy in HD patients.Results: We pooled data from 1,119 patients across four RCTs. Patients in the pridopidine group had a significantly lower Unified Huntington's Disease Rating Scale (UHDRS)-modified Motor Score (mMS) (MD −0.79, 95% CI = −1.46 to −0.11, p = 0.02) than those in the placebo group. Additionally, no differences were observed in the UHDRS-Total Motor Score (TMS) (MD −0.91. 95% CI = −2.03 to 0.21, p = 0.11) or adverse events (RR 1.06, 95% CI = 0.96 to 1.16, p = 0.24) in the pridopidine and placebo groups. In the subgroup analysis, the short-term (≤12 weeks) and long-term (&gt;12 weeks) subgroups exhibited similar efficacy and safety with no statistical significance in TMS, mMS, or adverse events. However, TMS (MD −1.50, 95% CI = −2.87 to −0.12, p = 0.03) and mMS (MD −1.03, 95% CI = −1.87 to −0.19, p = 0.02) were observed to be improved significantly when the dosage of pridopidine ≥90 mg/day. Additionally, pridopidine (≥90 mg/day) increased total adverse events (RR 1.11, 95% CI = 1.00 to 1.22, p = 0.04) compared with placebo. On this basis, we analyzed the incidence of various adverse events when the dosage was ≥90 mg/day. Nonetheless, these results were within the acceptable threshold, although patients developed symptoms, such as nasopharyngitis and insomnia.Conclusion: Pridopidine improved mMS and had no statistical significance in association with TMS or adverse events. Pridopidine (≥90 mg/day) improved TMS and mMS but increased adverse events, such as nasopharyngitis and insomnia. More RCTs were expected to assess pridopidine in HD.

scholarly journals Comparative Efficacy and Safety of Dopamine Agonists in Advanced Parkinson's Disease With Motor Fluctuations: A Systematic Review and Network Meta-Analysis of Double-Blind Randomized Controlled Trials

2021 ◽  
Vol 15 ◽  
Author(s):  
Xinglin Ruan ◽  
Fabin Lin ◽  
Dihang Wu ◽  
Lina Chen ◽  
Huidan Weng ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Dopamine Agonists ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Motor Fluctuations ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Troublesome Dyskinesia

Background: Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs).Methods and Findings: We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy (“ON” time without troublesome dyskinesia, “OFF” time, “ON” time, “UPDRS-III,” and “UPDRS-II”) and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of “ON” time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%).Conclusions: This network meta-analysis shows that apomorphine increased “ON” time without troublesome dyskinesia and decreased “OF” time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased “ON” time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.

Efficacy and Safety of Methylnaltrexone for the Treatment of Opioid-Induced Constipation: A Meta-analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
Ying-Ying Zhang ◽  
Rong Zhou ◽  
Wan-Jie Gu
Keyword(s):  
Abdominal Pain ◽  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Safety Outcome ◽  
Randomized Controlled ◽  
Safety Outcomes

Abstract Background: Opioid-induced constipation (OIC) is a distressing side effect during opioid analgesia and is mainly mediated by gastrointestinal μ opioid receptors. Methylnaltrexone, a peripheral μ opioid receptor antagonist with restricted ability to cross the blood-brain barrier, may alleviate OIC without reversing analgesia. We performed a meta-analysis to assess the efficacy and safety of methylnaltrexone for the treatment of OIC.Methods: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials that compared methylnaltrexone with placebo for the treatment of OIC. The primary efficacy outcome was rescue-free bowel movement (RFBM) within 4 hours after the first dose. Secondary efficacy outcomes included RFBM within 24 hours after the first dose, RFBM ≥3 times per week, and need take rescue laxatives. The primary safety outcome was any adverse events. Secondary safety outcomes included abdominal pain, diarrhea, nausea, vomiting, and flatulence. Relative risks (RR) and 95% confidence interval (CI) were pooled using random-effects model with the intention-to-treat principle. We used the GRADE approach to assess the certainty of the evidence.Results: Eight trials with 2,034 participants were included. Compared with placebo, methylnaltrexone significantly increased RFBM within 4 hours after the first dose (8 trials; 1,833 participants; RR 3.74, 95% CI 3.02-4.62; I2 = 0%; high-certainty evidence), RFBM within 24 hours after the first dose (2 trials; 614 participants; RR 1.98, 95% CI 1.52-2.58; I2 = 9%; moderate-certainty evidence), and RFBM ≥3 times per week (3 trials; 1,396 participants; RR 1.33, 95% CI 1.17-1.52; I2 = 0%; moderate-certainty evidence) and decreased need to take rescue laxatives (3 trials; 807 participants; RR 0.73, 95% CI 0.63-0.85; I2 = 0%; moderate-certainty evidence). For safety outcomes, there was no difference in any adverse events between the two groups (8 trials; 2,034 participants; RR 1.11, 95% CI 0.99-1.23; I2 = 34%; moderate-certainty evidence), including diarrhea, nausea, vomiting, and flatulence; but for the most commonly reported adverse events, the abdominal pain was higher in methylnaltrexone group than that in placebo group (6 trials; 1,813 participants; RR 2.30, 95% CI 1.29-4.08; I2 = 62%; moderate-certainty evidence).Conclusions: Methylnaltrexone is an effective and safe drug for treating OIC. But the safety of abdominal pain should be considered.Trial registration: PROSPERO (CRD42020187290).

scholarly journals Hydroxychloroquine plus standard of care compared with standard of care alone in COVID-19: a meta-analysis of randomized controlled trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bahman Amani ◽  
Ahmad Khanijahani ◽  
Behnam Amani
Keyword(s):  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Length Of Hospital Stay ◽  
Standard Of Care ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Significant Difference

AbstractThe efficacy and safety of Hydroxychloroquine (HCQ) in treating coronavirus disease (COVID-19) is disputed. This systematic review and meta-analysis aimed to examine the efficacy and safety of HCQ in addition to standard of care (SOC) in COVID-19. PubMed, the Cochrane Library, Embase, Web of sciences, and medRxiv were searched up to March 15, 2021. Clinical studies registry databases were also searched for identifying potential clinical trials. The references list of the key studies was reviewed to identify additional relevant resources. The quality of the included studies was evaluated using the Cochrane Collaboration tool and Jadad checklist. Meta-analysis was performed using RevMan software (version 5.3). Eleven randomized controlled trials with a total number of 8161 patients were identified as eligible for meta-analysis. No significant differences were observed between the two treatment groups in terms of negative rate of polymerase chain reaction (PCR) (Risk ratio [RR]: 0.99, 95% confidence interval (CI) 0.90, 1.08; P = 0.76), PCR negative conversion time (Mean difference [MD]: − 1.06, 95% CI − 3.10, 0.97; P = 0.30), all-cause mortality (RR: 1.09, 95% CI 1.00, 1.20; P = 0.06), body temperature recovery time (MD: − 0.64, 95% CI − 1.37, 0.10; P = 0.09), length of hospital stay (MD: − 0.17, 95% CI − 0.80, 0.46; P = 0.59), use of mechanical ventilation (RR: 1.12, 95% CI 0.95, 1.32; P = 0.19), and disease progression (RR = 0.82, 95% CI 0.37, 1.85; P = 0.64). However, there was a significant difference between two groups regarding adverse events (RR: 1.81, 95% CI 1.36, 2.42; P < 0.05). The findings suggest that the addition of HCQ to SOC has no benefit in the treatment of hospitalized patients with COVID-19. Additionally, it is associated with more adverse events.

scholarly journals Benefits and Risks of Chloroquine and Hydroxychloroquine in The Treatment of Viral Diseases: A Meta-Analysis of Placebo Randomized Controlled Trials

2020 ◽  
Author(s):  
Jing Wang ◽  
Li Yu ◽  
Kefeng Li
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Viral Diseases ◽  
Controlled Trials ◽  
Significant Heterogeneity ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Increased Risk

AbstractBackground and ObjectiveRecently, in the scramble to find drugs to treat COVID-19, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have rapidly gained the public’s attention. In this study, we conducted a meta-analysis of randomized clinical trials (RCTs) to evaluate the efficacy and safety of CQ and HCQ in the treatment of viral diseases.MethodsWe searched PubMed, EMBASE, Cochrane Central, Web of Science, Clinical Trials Registries, CNKI, Wanfang Data, CQVIP, and Preprint Servers through April 4, 2020, for randomized controlled trials (RCTs) that examined the efficacy and safety of CQ and HCQ against viral infection. We analyzed pooled data on the overall efficacy, the relative risks over the placebo, and the prevalence of adverse events. Trial sequential analysis (TSA) was also performed to evaluate the random errors in the meta-analysis. Potential moderators of drug-placebo efficacy differences were analyzed by meta-regression.ResultsThe analysis included 11 RCTs with 2613 adult patients. Both the plasma viral load (standard mean difference: 0.29, 95% CI: −1.19 - 1.76, P = 0.70) and the improvement of clinical symptoms (odds ratio: 2.36, 95% CI: 0.81 - 6.92, P = 0.11) were not different between the intervention and placebo arm. There was significant heterogeneity for the efficacy assessment, which was primarily explained by the mean patients’ age and the sample size. Compared to the placebo, CQ and HCQ had increased risk of mild adverse events (risk ratio: 1.51, 95% CI: 1.35 - 1.70, P < 0.05, TSA adjusted 95% CI: 1.31 - 2.19), which were statistically significant in nervous, integumentary, and gastrointestinal systems. The most common adverse events were observed in the nervous system, with the pooled prevalence of 31.4 % (95% CI: 10.5% - 56.7%).ConclusionsInsufficient data were available to support the antiviral efficacy of CQ and HCQ due to the high heterogeneity caused by patients’ age. Mild side effects are expected for the current antiviral dose regimens of CQ and HCQ. Treatment outcomes may be enhanced by better-selected patients based on age and well-controlled adverse events.This meta-analysis was registered on OSF (ID: https://osf.io/386aw)

scholarly journals The efficacy and safety of prophylactic corticosteroids for the prevention of adverse outcomes in patients undergoing heart surgery using cardiopulmonary bypass: a systematic review and meta-analysis of randomized controlled trials

2020 ◽  
Vol 57 (4) ◽  
pp. 620-627 ◽  
Author(s):  
Ka Ting Ng ◽  
Judith Van Paassen ◽  
Clare Langan ◽  
Deep Pramod Sarode ◽  
M Sesmu Arbous ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Adverse Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Site Infection ◽  
Efficacy And Safety ◽  
Randomized Controlled

Abstract Corticosteroids are often administered prophylactically to attenuate the inflammatory response associated with cardiac surgery using cardiopulmonary bypass (CPB). However, the efficacy and safety profile of corticosteroids remain uncertain. The primary aim of this systematic review and meta-analysis was to investigate the effect of corticosteroids on mortality in adult cardiac surgery using CPB. Secondary aims were to examine the effect of corticosteroids on myocardial adverse events, pulmonary adverse events, atrial fibrillation, surgical site infection, gastrointestinal bleeding and duration of stay in the intensive care unit and hospital. Randomized controlled trials (RCTs) were systematically searched in electronic databases (MEDLINE, EMBASE, CINAHL, CENTRAL and Web of Science) from their inception until March 2019. Observational studies, case reports, case series and literature reviews were excluded. Sixty-two studies (n = 16 457 patients) were included in this meta-analysis. There was no significant difference in mortality between the corticosteroid and placebo groups [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81–1.14; P = 0.65, participants = 14 693, studies = 24, evidence of certainty: moderate]. Compared to those receiving a placebo, patients who were given corticosteroids had a significantly higher incidence of myocardial adverse events (OR 1.17, 95% CI 1.03–1.33; P = 0.01, participants = 14 512, studies = 23) and a lower incidence of pulmonary adverse events (OR 0.86, 95% CI 0.75–0.98; P = 0.02, participants = 13 426, studies = 17). The incidences of atrial fibrillation (OR 0.87, 95% CI 0.81–0.94; P &lt; 0.001, participants = 14 148, studies = 24) and surgical site infection (OR 0.81, 95% CI 0.73–0.90; P &lt; 0.001, participants = 13 946; studies = 22) were all lower in patients who were given corticosteroids. In the present meta-analysis of 62 RCTs (16 457 patients), including the 2 major RCTs (SIRS and DECS trials: 12 001 patients), we found that prophylactic corticosteroids in cardiac surgery did not reduce mortality. The clinical significance of an increase in myocardial adverse events remains unclear as the definition of a relevant myocardial end point following cardiac surgery varied greatly between RCTs.

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