Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis.

This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.

Cardiovascular benefits of statin plus ezetimibe combination therapy versus statin monotherapy in acute coronary syndrome: a meta-analysis of randomized controlled trials

BACKGROUND: The efficacy of adding ezetimibe to statin therapy for event reduction in patients with acute coronary syndromes (ACS) remains a topic of ongoing debate. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ezetimibe plus statin versus statin monotherapy in patients with ACS. We searched PubMed, Embase, and Cochrane for eligible trials. Random-effects model was used to calculate the risk ratios (RRs), with 95% confidence intervals (CIs). Statistical analyses were performed using RStudio version 4.2.3. RESULTS: Six RCTs comprising 20,574 patients with ACS were included, of whom 10,259 (49.9%) were prescribed ezetimibe plus statin. The patient population had an average age of 63.8 years and 75.1% were male. Compared with statin monotherapy, ezetimibe plus statin significantly reduced major adverse cardiovascular events (MACE) (RR 0.93; 95% CI 0.90-0.97; p<0.01) and non-fatal myocardial infarction (RR 0.88; 95% CI 0.81-0.95; p<0.01). There was no significant difference between groups for revascularization (RR 0.94; 95% CI 0.88-1.01; p=0.07), all-cause death (RR 0.87; 95% CI 0.63-1.21; p=0.42), or unstable angina (RR 1.05; 95% CI 0.86-1.27; p=0.64). CONCLUSION: In this meta-analysis of patients with ACS, the combination of ezetimibe plus statin was associated with a reduction in MACE and non-fatal myocardial infarction, compared with statin monotherapy.

Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials.

BACKGROUND: The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated. METHODS: We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Three studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49-0.84; p < 0.01) and overall survival (OS) rate (HR 0.72; 95% CI 0.62-0.83; p < 0.01) were significant in favor of the Zolbetuximab group. Regarding effectiveness, the Objective Response Rate (ORR) was (OR 1.15; 95% CI 0.87-1.53; p = 0.34). CONCLUSIONS: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of Zolbetuximab alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with advanced CLDN18.2-positive GC/GEJ cancer.

Continuous Glucose Monitoring Systems in Noninsulin-Treated People with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction: Continuous glucose monitoring (CGM) has shown favorable outcomes in patients with type 2 diabetes (T2D) who are on insulin therapy. However, the efficacy of CGM in managing glucose levels in noninsulin-treated people with T2D remains controversial. Methods: PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing CGM to self-monitoring of blood glucose (SMBG) in people with T2D not using insulin. We computed weighted mean differences (WMDs) and standard mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Statistical analyses were performed using R version 4.2.3. Results: We included six RCTs comprising 407 noninsulin-treated people with T2D of whom 228 were randomized to CGM. Diabetes duration ranged from 5.4 to 13.9 years. The mean age was 57.9 years and the mean body mass index was 30.8 kg/m2. Four trials used real-time CGM (rt-CGM) and two intermittent scanning CGM (is-CGM). Compared with SMBG, CGM significantly reduced the glycated hemoglobin level (WMD -0.31%; 95% CI -0.42 to -0.21; I2 = 0%), glucose level (WMD -11.16 mg/dL; 95% CI -19.94 to -2.39; I2 = 0%), time in hypoglycemia level 2 (WMD -0.28%; 95% CI -0.52 to -0.03; I2 = 91%), glucose time >180 mg/dL (WMD -7.75%; 95% CI -12.04 to -3.45; I2 = 0%), and the standard deviation of glucose variation (WMD -4.00 mg/dL; 95% CI -6.86 to -1.14; I2 = 0%). CGM also increased time in range (WMD 8.63%; 95% CI 4.54-12.71; I2 = 0%) and treatment satisfaction (SMD 0.79; 95% CI 0.54-1.05; I2 = 0%). Conclusion: In this meta-analysis, rt-CGM and is-CGM were associated with improvement in glycemic control in people with T2D not using insulin when compared to SMBG.

Endoscopic Third Ventriculostomy versus Ventriculoperitoneal Shunt in Patients with Obstructive Hydrocephalus: An Updated Systematic Review and Meta-Analysis.

Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) are surgical methods for treating obstructive hydrocephalus. However, there is still disagreement regarding the most effective technique, in terms of both operative success and postoperative complications. Therefore, we performed a systematic review and meta-analysis to compare the efficacy and safety of these two methods in patients with obstructive hydrocephalus. We performed a systematic search of the PubMed, Scopus, and Cochrane Library databases. Randomized clinical trials (RCTs) comparing ETV and VPS in pediatric or adult patients with obstructive hydrocephalus were included. The outcomes included were operative success, postoperative cerebrospinal fluid leak, postoperative infection, postoperative or intraoperative bleeding, blockage rate, and mortality. The risk ratio (RR) was calculated with a 95% confidence interval (CI). Heterogeneity was evaluated with I 2 statistics. We used a fixed-effects model for outcomes with I 2 < 25% and DerSimonian and Laird random-effects model for other conditions. The Cochrane collaboration tool for assessing the risk of bias in randomized trials was used for risk-of-bias assessment. R, version 4.2.1, was used for statistical analyses. Of the 2,353 identified studies, 5 RCTs were included, involving 310 patients with obstructive hydrocephalus, of which 163 underwent ETV. There was a significant difference in favor of ETV for postoperative infection (risk ratio [RR]: 0.11; 95% confidence interval [CI]: 0.04-0.33; p < 0.0001; I 2 = 0%) and blockage rate (RR: 0.15; 95% CI: 0.03-0.75; p = 0.02; I 2 = 53%). Meanwhile, there was no significant difference between groups for the postoperative or intraoperative bleeding (RR: 0.44; 95% CI: 0.17-1.15; p = 0.09; I 2 = 0%), postoperative cerebrospinal fluid leak (RR: 0.65; 95% CI: 0.22-1.92; p = 0.44; I 2 = 18%), operative success (RR: 1.18; 95% CI: 0.77-1.82; p = 0.44; I 2 = 84%), and mortality (RR: 0.19; 95% CI: 0.03-1.09; p = 0.06; I 2 = 0%). Three RCTs had some concerns about the risk of bias and one RCT had a high risk of bias due to the process of randomization and selection of reported results. Thus, this meta-analysis of RCTs evaluating ETV compared with VPS demonstrated that although there is no superiority of ETV in terms of operative success, the incidence of complications was significantly higher in patients who underwent VPS. Our results suggest that the use of ETV provides greater benefits for the treatment of obstructive hydrocephalus. However, more RCTs are needed to corroborate the superiority of ETV.

PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51-0.86) and event-free survival (HR 0.53; 95% CI 0.43-0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86-10.61) and pathological complete response (OR 8.82; 95% CI 4.51-17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69-0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.

Surgical versus non-surgical treatment of flail chest: a meta-analysis of randomized controlled trials.

PURPOSE: Conflicting evidence exists on the choice of surgical or non-surgical treatment of flail chest injuries. We aimed to perform a meta-analysis comparing outcomes in patients presenting flail chest undergoing surgical or non-surgical treatment. METHODS: Embase, PubMed, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing surgery to no surgery in patients with acute unstable chest wall injuries. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). Random effects meta-analyses were performed. Heterogeneity was assessed using I2 statistics. RESULTS: Six RCTs (544 patients) were included, and surgical treatment was used in 269 (49.4%). Compared to no surgery, surgery reduced mechanical ventilation days (WMD - 4.34, 95% CI - 6.98, - 1.69; p < 0.01; I2 = 87%; GRADE: very low; PI - 13.51, 4.84); length of intensive care unit stay (WMD - 4.62, 95% CI - 7.19, - 2.05; p < 0.01; I2 = 78%; GRADE: low; PI - 12.86, 3.61) and the incidence of pneumonia (RR 0.50, 95% CI 0.31, 0.81; p = 0.005; I2 = 54%; GRADE: moderate; PI 0.13, 1.91). No difference in mortality (RR 0.56, 95% CI 0.19, 1.65; p = 0.27; I2 = 23%; GRADE: moderate; PI 0.04, 7.25), length of hospital stay (WMD - 5.39, 95% CI - 11.38, - 0.60; p = 0.08; I2 = 89%; GRADE: very low; PI - 11.38, 0.60), or need for tracheostomy (RR 0.59, 95% CI 0.34, 1.03; p = 0.06; I2 = 54%; GRADE: moderate; PI 0.11, 3.24) was found. CONCLUSIONS: Our results suggest that surgical treatment is advantageous compared to non-surgical treatment for patients with flail chest secondary to rib fractures.