Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk. Familial hypercholesterolemia (FH) further complicates its management, necessitating additional lipid-lowering therapies. Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, has emerged as a potential treatment, particularly for patients with FH, by effectively reducing LDL-C and triglyceride levels. This meta-analysis aimed to evaluate the efficacy and safety of evinacumab across diverse patient populations. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, relevant randomized controlled trials (RCTs) were systematically retrieved from multiple databases until November 24, 2023. The inclusion criteria were studies comparing evinacumab (at doses of 5 and 15 mg) to placebo, with outcomes focusing on lipid levels and adverse events. Standardized protocols were employed for data extraction and quality assessment, and statistical analysis was conducted using RevMan software. RESULTS: Four RCTs, involving 270 patients, were included in the analysis. The analysis revealed significant reductions in lipid markers, particularly with the 15-mg dose of evinacumab, including triacylglycerols (standard mean difference [SMD] = -6.09, 95% confidence interval [CI] - 14.53 to 2.36, P = 0.16), total cholesterol (SMD = - 6.20, 95% CI - 11.53 to - 0.88, P = 0.02), high-density lipoprotein cholesterol (SMD = - 0.79, 95% CI - 1.27 to - 0.31, P = 0.001), LDL-C (SMD = - 4.58, 95% CI - 9.13 to - 0.03, P = 0.05), apolipoprotein (Apo) B (SMD = - 4.01, 95% CI - 7.53 to - 0.46, P = 0.03), and Apo C3 (SMD = - 7.67, 95% CI - 12.94 to - 2.41, P = 0.004). Adverse event analysis revealed no significant association, indicating good tolerability. CONCLUSION: High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability. Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease.

Evaluating the efficacy and safety of nivolumab and ipilimumab combination therapy compared to nivolumab monotherapy in advanced cancers (excluding melanoma): a systemic review and meta-analysis.

BACKGROUND: Nivolumab (Nivo) and ipilimumab (Ipi) have revolutionized cancer treatment by targeting different pathways. Their combination shows promising results in various cancers, including melanoma, but not all studies have demonstrated significant benefits. A meta-analysis was performed to assess the effectiveness and safety of Nivo-Ipi compared to Nivo alone in advanced cancer types (excluding melanoma). METHODS: Following PRISMA guidelines, we conducted a meta-analysis up to September 30, 2023, searching databases for randomized controlled trials (RCTs). We focused on advanced solid malignancies (excluding melanoma) with specific Nivo and Ipi dosing. Primary outcomes were overall survival (OS), progression-free survival (PFS), grades 3-4 adverse events (AEs), and treatment-related discontinuations. Secondary outcomes included specific adverse events. Statistical analysis in Review Manager included hazard ratio (HR) and risk ratio (RR), assessing heterogeneity (Higgins I2). RESULTS: Nine RCTs, involving 2152 patients covering various malignancies, were analyzed. The Nivo plus Ipi group exhibited a median OS of 12.3 months and a median PFS of 3.73 months, compared to monotherapy with 11.67 months and 3.98 months, respectively. OS showed no significant difference between Nivo and Ipi combination and Nivo alone (HR = 0.97, 95% CI: 0.88 to 1.08, p = 0.61). PFS had a slight improvement with combination therapy (HR = 0.91, 95% CI: 0.82 to 1.00, p = 0.04). Treatment-related cumulative grades 3-4 adverse events were higher with Nivo and Ipi (RR = 1.52, 95% CI: 1.30 to 1.78, p < 0.00001), as were treatment-related discontinuations (RR = 1.99, 95% CI: 1.46 to 2.70, p < 0.0001). Hepatotoxicity (RR = 2.42, 95% CI: 1.39 to 4.24, p = 0.002), GI toxicity (RR = 2.84, 95% CI: 1.44 to 5.59, p = 0.002), pneumonitis (RR = 2.29, 95% CI: 1.24 to 2.23, p = 0.008), dermatitis (RR = 2.96, 95% CI: 1.08 to 8.14, p = 0.04), and endocrine dysfunction (RR = 6.22, 95% CI: 2.31 to 16.71, p = 0.0003) were more frequent with Nivo and Ipi. CONCLUSIONS: Combining nivolumab and ipilimumab did not significantly improve overall survival compared to nivolumab alone in advanced cancers (except melanoma). However, it did show slightly better PFS at the cost of increased toxicity, particularly grades 3-4 adverse events. Specific AEs occurred more frequently in the combination group. Further trials are needed to fully assess this combination in treating advanced cancers.

Preoperative anxiety management in pediatric patients: a systemic review and meta-analysis of randomized controlled trials on the efficacy of distraction techniques.

Background: This study addresses the pervasive issue of heightened preoperative anxiety in healthcare, particularly among pediatric patients. Recognizing the various sources of anxiety, we explored both pharmacological and nonpharmacological interventions. Focusing on distraction techniques, including active and passive forms, our meta-analysis aimed to provide comprehensive insights into their impact on preoperative anxiety in pediatric patients. Methods: Following the PRISMA and Cochrane guidelines, this meta-analysis and systematic review assessed the efficacy of pharmaceutical and distraction interventions in reducing pain and anxiety in pediatric surgery. This study was registered on PROSPERO (CRD42023449979). Results: This meta-analysis, comprising 45 studies, investigated pharmaceutical interventions and distraction tactics in pediatric surgery. Risk of bias assessment revealed undisclosed risks in performance and detection bias. Distraction interventions significantly reduced preoperative anxiety compared to control groups, with notable heterogeneity. Comparison with Midazolam favored distraction techniques. Subgroup analysis highlighted varied efficacies among distraction methods, with a notable reduction in anxiety levels. Sensitivity analysis indicated stable results. However, publication bias was observed, suggesting a potential reporting bias. Conclusion: Our study confirms distraction techniques as safe and effective for reducing pediatric preoperative anxiety, offering a valuable alternative to pharmacological interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=449979, PROSPERO [CRD42023449979].

Efficacy and safety of Ciprofol compared with Propofol during general anesthesia induction: A systematic review and meta-analysis of randomized controlled trials (RCT).

BACKGROUND: Ciprofol, a newer entrant with similarities to propofol, has shown promise with a potentially improved safety profile, making it an attractive alternative for induction of general anesthesia. This meta-analysis aimed to assess the safety and efficacy of ciprofol compared with propofol during general anesthesia induction. METHODS: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to July 2023 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. RESULTS: Thirteen Randomized Controlled Trials (RCTs) encompassing a total of 1998 participants, were included in our analysis. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for postoperative hypertension, bradycardia, or tachycardia. CONCLUSION: In conclusion, Ciprofol is not inferior to Propofol in terms of its effectiveness in general anesthesia. Ciprofol emerges as a valuable alternative sedative with fewer side effects, especially reduced injection pain, when compared to Propofol. SUMMARY: Propofol, frequently utilized as an anesthetic, provides swift onset and quick recovery. However, it has drawbacks such as a narrow effective dosage range and a high occurrence of adverse effects, particularly pain upon injection. Ciprofol, a more recent drug with propofol-like properties, has demonstrated promise and may have an improved safety profile, making it a compelling alternative for inducing general anesthesia. This meta-analysis compared the safety and effectiveness of Ciprofol with Propofol for general anesthesia induction in a range of medical procedures, encompassing thirteen Randomized Controlled Trials (RCTs) and 1998 individuals. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for hypertension, bradycardia, or tachycardia. In conclusion, ciprofol is equally effective at inducing and maintaining general anesthesia as propofol. When compared to propofol, ciprofol is a better alternative sedative for operations including fiberoptic bronchoscopy, gynecological procedures, gastrointestinal endoscopic procedures, and elective surgeries because it has less adverse effects, most notably less painful injections.

Meta-analysis on performance of ABC and GARFIELD-AF compared to CHA2DS2-VASc and HAS-BLED in anticoagulated atrial fibrillation patients.

BACKGROUND: When high thromboembolic and bleeding risks coexist, the former tends to influence physicians' decision making for anti-coagulation therapy. However, the ideal is to weigh the risk of major bleeding and stroke together to ensure effective anti-coagulation treatment, which is a limitation of traditional guideline recommended CHA2DS2-VASc and HAS-BLED. This meta-analysis assesses the performance of the two new scores - ABC and GARFIELD-AF compared to CHA2DS2-VASc and HAS-BLED for major bleeding and stroke outcomes in patients with atrial fibrillation (AF) on anticoagulation therapy. METHODS: MEDLINE and Cochrane central were searched from 2010 to February 2023 that compared GARFIELD-AF and/or ABC with CHA2DS2-VASc and/or HAS-BLED scores using C-statistics to assess their discriminative ability. RESULTS: 12 studies were included in this meta-analysis. When assessing stroke risk prediction, GARFIELD-AF stroke (C-Statistic: 0.71; 95 % CI: 0.70-0.72; I2 = 0 %, p < 0.05) was found to be significantly better than ABC-stroke (C-Statistic: 0.67; 95 % CI: 0.65-0.68; I2 = 0 %, p < 0.05), and CHA2DS2-VASc (C-Statistic: 0.64; 95 % CI: 0.60-0.67; I2 = 92 %, p < 0.05). Additionally, when assessing bleeding risk prediction, ABC-bleeding (C-Statistic: 0.66; 95 % CI: 0.61-0.70; I2 = 84 %, p < 0.05), GARFIELD-AF (C-Statistic: 0.64; 95 % CI: 0.60-0.68; I2 = 95 %, p < 0.05), and HAS-BLED (C-Statistic: 0.64; 95 % CI: 0.62-0.66; I2 = 85 %, p < 0.05) all showed equivalent performances. CONCLUSION: The GARFIELD-AF stroke score showed superior performance to the well-established CHA2DS2-VASc score as well as the ABC-stroke score. Therefore, new guidelines should favor GARFIELD-AF use in clinical practice.

Analyzing safety and effectiveness of Mavacamten in comparison with placebo for managing hypertrophic cardiomyopathy: a systemic review and meta-analysis.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a hereditary myocardial disorder, often due to sarcomere gene mutations, characterized by the left ventricular hypertrophy. Current treatments offer symptomatic relief but lack specificity. Mavacamten, an allosteric inhibitor, has shown significant improvements in HCM patients in trials, reducing the requirement for invasive treatments. This meta-analysis assesses Mavacamten's efficacy and safety as a targeted HCM intervention. METHODS: This study examined four randomized controlled trials comparing Mavacamten to placebo in HCM patients. Each trial had a unique primary endpoint, and secondary outcomes included improvements in NYHA-FC, eligibility for septal reduction therapy (SRT) or undergoing it, adverse events (serious and treatment-related), atrial fibrillation, and non-sustained ventricular tachycardia. Statistical analysis involved calculating risk ratios (RRs) and assessing heterogeneity. RESULTS: The four included studies showed minimal risk of bias and involved 503 patients with HCM (273 Mavacamten and 230 placebo). Mavacamten significantly increased the primary endpoint (RR 2.15, 95% CI 1.20-3.86, P = 0.01) and ≥ 1 NYHA-FC class (RR 2.21, 95% CI 1.48-3.3, P = 0.0001). Mavacamten group had lower rates of SRT compared to those receiving placebo (RR, 0.30, 95% CI 0.22-0.40; P < 0.00001). No significant differences existed in rates adverse events between the Mavacamten and placebo groups. CONCLUSIONS: Our study suggests that Mavacamten may have therapeutic benefits for HCM patients, as indicated by its positive impact on certain endpoints. Further research with larger samples, longer follow-up, and comprehensive analysis is needed to understand Mavacamten's safety and efficacy in HCM patients.