Clinical Efficacy and Safety of Propranolol in the Prevention and Treatment of Retinopathy of Prematurity: A Meta-Analysis of Randomized Controlled Trials

Objective: To perform a meta-analysis of randomized controlled trials verifying clinical efficacy and safety of propranolol in pre-term newborns with retinopathy of prematurity (ROP).Methods: We searched the literature databases (Pubmed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang, VIP, CBM) for publications before August 10, 2020, and the World Health Organization's International Clinical Trials Registry and ClinicalTrials.gov for ongoing trials. Randomized controlled trials (RCTs) of propranolol for the prevention or treatment of ROP were included. The quality of the included studies was primarily assessed by the RCT tool of the Cochrane Collaboration. The included studies were quantified using a meta-analysis of relative risk (RR) estimated with a random effect model.Results: Our original search identified 171 articles, and five studies met our criteria. A meta-analysis was performed that showed that infants orally treated with propranolol had a decreased risk of disease progression: stage progression had an RR = 0.65 [95% confidence interval (CI), 0.47–0.88]), plus disease had an RR = 0.43 [95% CI, 0.22–0.82]. The demands for additional treatments had similar protective results: laser photocoagulations had an RR = 0.55 [95% CI, 0.35–0.86]), and intravitreal injection of anti-vascular endothelial growth factor had an RR = 0.45 [95% CI, 0.22–0.90]). The oral administration of propranolol was associated with an increased risk of adverse events (RR = 2.01 [95% CI, 1.02–3.97]). High-risk adverse events included bradycardia, hypotension, not gaining enough weight, bronchospasm, hypoglycemia, apnea, and increasing ventilator need. Subgroup analysis of ROP phases and stages found that the risk in stage 2 ROP of the second phase and the individual risk factors (stage progression, RR = 0.42 [95% CI, 0.27–0.65]; plus disease, RR = 0.40 [95% CI, 0.17–0.93]; laser photocoagulation, RR = 0.31 [95% CI, 0.14–0.68]) have statistically significant differences compared with other phases and stages.Conclusions: Pre-term newborns with ROP, especially in stage 2 ROP of the second phase, who were orally given propranolol have a reduced risk of disease progression and demand for additional treatments, but the safety needs more attention.

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

European Journal of Preventive Cardiology ◽

10.1177/2047487320930585 ◽

2020 ◽

pp. 204748732093058 ◽

Cited By ~ 3

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

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

Frontiers in Neurology ◽

10.3389/fneur.2021.658123 ◽

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 (>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.

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

10.21203/rs.3.rs-100123/v1 ◽

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).

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

Scientific Reports ◽

10.1038/s41598-021-91089-3 ◽

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.

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

10.1101/2020.04.13.20064295 ◽

2020 ◽

Cited By ~ 1

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)

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Does the Source of Mesenchymal Stem Cell Have an Effect in the Management of Osteoarthritis of the Knee? Meta-Analysis of Randomized Controlled Trials

Cartilage ◽

10.1177/1947603520951623 ◽

2020 ◽

pp. 194760352095162

Author(s):

Madhan Jeyaraman ◽

Sathish Muthu ◽

Parvez Ahmad Ganie

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Adverse Events ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Cochrane Library ◽

Controlled Trials ◽

Efficacy And Safety ◽

Osteoarthritis Of Knee ◽

Randomized Controlled

Study Design Meta-analysis. Objectives To compare the efficacy and safety of bone marrow(BM)–derived mesenchymal stem cell(MSCs) and adipose-derived(AD) MSCs in the management of osteoarthritis of knee from randomized controlled trials(RCTs) available in the literature. Materials and Methods We conducted electronic database searche from PubMed, Embase, and Cochrane Library till May 2020 for RCTs analyzing the efficacy and safety of MSCs in management of osteoarthritis of knee. Visual Analog Score(VAS) for Pain, Western Ontario McMaster Universities Osteoarthritis Index(WOMAC), Lysholm Knee Scale(Lysholm), Whole-Organ Magnetic Resonance Imaging Score(WORMS), Knee Osteoarthritis Outcome Score(KOOS), and adverse events were the outcomes analyzed. Analysis was performed in R platform using OpenMeta[Analyst] software. Results Nineteen studies involving 811 patients were included for analysis. None of the studies compared the source of MSCs for osteoarthritis of knee and results were obtained by pooled data analysis of both sources. At 6 months, AD-MSCs showed significantly better VAS( P<0.001, P=0.069) and WOMAC( P=0.134, P=0.441) improvement than BM-MSCs, respectively, compared to controls. At 1 year, AD-MSCs outperformed BM-MSCs compared to their control in measures like WOMAC( P=0.007, P=0.150), KOOS( P<0.001; P=0.658), and WORMS( P<0.001, P=0.041), respectively. Similarly at 24 months, AD-MSCs showed significantly better Lysholm score( P=0.037) than BM-MSCs( P=0.807) although VAS improvement was better with BM-MSCs at 24 months( P<0.001). There were no significant adverse events with either of the MSCs compared to their controls. Conclusion Our analysis establishes the efficacy, safety, and superiority of AD-MSC transplantation, compared to BM-MSC, in the management of osteoarthritis of knee from available literature. Further RCTs are needed to evaluate them together with standardized doses.

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A Meta-Analysis of Therapeutic Efficacy and Safety of Gabapentin in the Treatment of Postherpetic Neuralgia from Randomized Controlled Trials

BioMed Research International ◽

10.1155/2018/7474207 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Meng Zhang ◽

Cun-Xiang Gao ◽

Ke-Tao Ma ◽

Li Li ◽

Zhi-Gang Dai ◽

...

Keyword(s):

Placebo Group ◽

Adverse Events ◽

Randomized Controlled Trials ◽

Postherpetic Neuralgia ◽

Clinical Effect ◽

Meta Analysis ◽

Controlled Trials ◽

Efficacy And Safety ◽

Clinical Database ◽

Randomized Controlled

Objective. The study aims to systematically evaluate the clinical effect of gabapentin in the treatment of postherpetic neuralgia (PHN). Method. Data were retrieved electronically from PubMed, Embase, CNKI, the China Biomedical Database, and the Library of Clinical Database, beginning from the time of inception to April 2017, in order to collect data on randomized controlled trials (RCTs) of gabapentin and placebo in PHN treatment. Results. A total of 11 RCTs (2376 people) were retrieved. The gabapentin group reported significantly reduced pain intensity [MD=−0.91, 95% CI −1.32 to −0.51, P<0.00001] compared with the placebo group. Those treated with gabapentin also experienced significantly improved sleep quality [SMD=−0.44, 95% CI −0.66 to −0.23, P<0.0001], but were more likely to experience incidence of adverse events, such as somnolence, dizziness, and peripheral edema. Results of the subgroup analysis showed that the source of heterogeneity may be related to the formulations of the drug. Conclusion. Gabapentin can be used to effectively and safely treat PHN.

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Efficacy and safety of 18 anti-osteoporotic drugs in the treatment of patients with osteoporosis caused by glucocorticoid: A network meta-analysis of randomized controlled trials

PLoS ONE ◽

10.1371/journal.pone.0243851 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243851

Author(s):

Zhiming Liu ◽

Min Zhang ◽

Zhubin Shen ◽

Junran Ke ◽

Ding Zhang ◽

...

Keyword(s):

Vertebral Fracture ◽

Adverse Events ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Current Evidence ◽

Cochrane Library ◽

Controlled Trials ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Different Types

Background Glucocorticoids are widely used in a variety of diseases, especially autoimmune diseases and inflammatory diseases, so the incidence of glucocorticoid-induced osteoporosis is high all over the world. Objectives The purpose of this paper is to use the method of network meta-analysis (NMA) to compare the efficacy of anti-osteoporosis drugs directly and indirectly, and to explore the advantages of various anti-osteoporosis drugs based on the current evidence. Methods We searched PubMed, Embase and Cochrane Library for randomized controlled trials (RCTs), of glucocorticoid-induced osteoporosis (GIOP) and compared the efficacy and safety of these drugs by NMA. The risk ratio (RR) and its 95% confidence interval (CI) are used as the influence index of discontinuous data, and the standardized mean difference (SMD) and its 95% CI are used as the influence index of continuous data. The statistical heterogeneity was evaluated by the calculated estimated variance (τ2), and the efficacy and safety of drugs were ranked by the surface under the cumulative ranking curve (SUCRA). The main outcome of this study was the incidence of vertebral fracture after taking several different types of drugs, and the secondary results were the incidence of non-vertebral fracture and adverse events, mean percentage change of lumbar spine (LS) and total hip (TH)bone mineral density (BMD) from baseline to at least 12 months. Results Among the different types of anti-GIOP, teriparatide (SUCRA 95.9%) has the lowest incidence of vertebral fracture; ibandronate (SUCRA 75.2%) has the lowest incidence of non-vertebral fracture; raloxifene (SUCRA 98.5%) has the best effect in increasing LS BMD; denosumab (SUCRA 99.7%) is the best in increasing TH BMD; calcitonin (SUCRA 92.4%) has the lowest incidence of serious adverse events. Conclusions Teriparatide and ibandronate are effective drugs to reduce the risk of vertebral and non-vertebral fractures in patients with GIOP. In addition, long-term use of raloxifene and denosumab can increase the BMD of LS and TH.

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