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.

Efficacy of the hybrid closedloop insulin delivery system in children and adolescents with type 1 diabetes: a meta-analysis with trial sequential analysis.

The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucoselevel was > 180 mg/dL (WMD-10.46%, 95% CI-13.99 to-6.93%) and the mean levels of glucose (WMD-16.67 mg/dL, 95% CI-22.25 to-11.09 mg/dL) and HbA1c (WMD-0.50%, 95% CI-0.68 to-0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or <54 mg/dL or number of episodes of ketoacidosis, hyperglycemia, and hypoglycemia. In this meta-analysis, HCL compared with control therapies was associated with improved time in range and HbA1c control in children and adolescents with T1D and a similar profile of side effects. These findings support the efficacy of HCL in the treatment of T1D in this population.

Intracardiac echography-guided fluoroless ablation versus conventional fluoroscopy-guided ablation for cardiac arrhythmias: a systematic review and meta-analysis

BACKGROUND: Intracardiac echocardiography (ICE) has improved catheter ablation procedures, reducing reliance on fluoroscopy. Yet, the efficacy and safety of zero-fluoroscopy (ZF) procedures remain uncertain. METHODS: We conducted a systematic review and meta-analysis comparing ZF ablation procedures guided by ICE vs. conventional techniques regarding efficacy and safety outcomes. PubMed, Cochrane, and embase were searched. A random-effects model was used to calculate risk ratios (RRs), odds ratios (OR) and mean differences (MDs) with 95% confidence intervals (CI). RESULTS: We includedfourteen studies with 1,919 patients of whom 1,023 (58.72%) performed ZF ablation using ICE. We found a significant reduced ablation time (SMD -0.18; 95% CI -0.31;-0.04; p=0.009), procedure time (MD -7.54; 95% CI -14.68;-0.41; p=0.04), fluoroscopic time (MD -2.52; 95% CI -3.20;-1.84; p<0.001) in patients treated with ZF approach compared with NZF approach. However, there was no significant difference between the two groups in acute success rate (RR 1.00; 95% CI 0.99-1.01; p=0.85), long-term success rate (RR 0.99; 95% CI 0.93-1.05; p=0.77) and complications (RR 0.84, 95% CI: 0.48-1.46; p = 0.54). CONCLUSION: Our findings suggest that among patients undergoing arrhythmia ablation, fluoroscopy-free ICE-guided technique reduces procedure time and radiation exposure with comparable short and long-term success rates and complications.

Cardiovascular benefits of GLP-1 receptor agonists in patients who are obese or overweight: a meta-analysis of randomized controlled

Backgroun|D: GLP-1 receptor agonists (GLP-1 RAs) have emerged as an effective therapeutic class for weight loss. However, the efficacy of these agents in cardiovascular endpoints among patients who are obese or overweight requires additional investigation. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing GLP-1 RAs vs. placebo in patients who are obese or overweight. PubMed, Cochrane, and Embase were searched. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: A total of 12 RCTs were included, with 12,908 patients. Compared with placebo, GLP-1 RAs were associated with significant reductions in systolic blood pressure (MD -4.45 mmHg; 95% CI -5.31, -3.60; p<0.01) and diastolic blood pressure (MD -1.43 mmHg; 95% CI -2.63, -0.22; p=0.02). There were no significant differences between groups for unstable angina (UA) (RR 0.90; 95% CI 0.29-2.84; p=0.86), stroke (RR 0.65; 95% CI 0.28-1.49; p=0.30), atrial fibrillation (AF) (RR 0.87; 95% CI 0.33-2.30; p=0.78), myocardial infarction (MI) (RR 0.57; 95% CI 0.17-1.90; p=0.36), or deep vein thrombosis (RR 0.45; 95% CI 0.08-2.65; p=0.38). CONCLUSION: In patients who are overweight or obese, GLP-1 receptor agonists reduce systolic and diastolic blood pressure, with a neutral effect on the incidence of UA, stroke, AF, MI, and deep vein thrombosis.

Cardiovascular impact of cancer in patients with atrial fibrillation on warfarin: a systematic review and meta-analysis

BACKGROUND: The impact of cancer on patients with atrial fibrillation (AF) on warfarin remains a topic of ongoing debate. METHODS: We performed a systematic review and meta-analysis exploring the effect of cancer in patients with AF on warfarin. 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: Five trials comprising 90,572 patients were included, of whom 12,239 (13.5%) had a personal history of cancer. The patient population had an average age of 72.7 years and 59.6% were male. A history of cancer was associated with a significant increase in any bleeding (RR 1.33; 95% CI 1.15- 1.53; p<0.01). There were no significant differences between groups for stroke (RR 1.05; 95% CI 0.86- 1.29; p=0.61), major bleeding (RR 1.44; 95% CI 0.95-2.18; p=0.09), cardiovascular (CV) death (RR 0.91; 95% CI 0.59-1.41; p=0.67), myocardial infarction (MI) (RR 1.42; 95% CI 0.96-2.10; p=0.08), gastrointestinal (GI) bleeding (RR 1.74; 95% CI 0.77-3.92; p=0.18), or all-cause death (RR 1.57; 95% CI 0.99-2.49; p=0.06). CONCLUSION: Among patients with AF on warfarin, a history of cancer is associated with an increased risk of any bleeding, with no significant effect on stroke, major bleeding, CV death, MI, GI bleeding, and all-cause death.

Cardioneuroablation for reflex syncope: a systematic review and single-arm meta-analysis

BACKGROUND: Reflex syncope reduces quality of life and leads to fall-related injuries, with no highly effective treatment. In this context, cardioneuroablation (CNA) presents as a promising therapy for these patients. METHODS: We searched PubMed, Embase and Cochrane Central for studies that evaluated safety and efficacy outcomes related to CNA procedures. Two reviewers independently performed study selection, data extraction and assessment of bias. Generalized linear mixed models was used. We performed a single-arm meta-analysis using R version 4.2.3. RESULTS: A total of 25 studies comprising 871 patients were included. The mean follow-up ranged from 8 to 40 months. Mean age ranged from 32.9 to 53.9 years and 541 (62.1%) were female. The ablation target was biatrial in 302 patients (34%), left atrium only in 433 (49%), and right atrium only in 136 (15%). The freedom from syncope was 94% (95% confidence interval (CI) 90.13-97.00; P<0.01). Left and right atrial CNA was associated with a significant higher freedom from syncope (96.03%; 95% CI 93.13-97.73) than left atrial ablation only (94.61%; 95% CI 82.88-98.45) and right ablation only (84.53%; 95% CI 74.30-91.18). Peri-procedural adverse event occurred on 1.4% (95% CI 0.44- 4.50). CONCLUSION: Our findings suggest that in patients with reflex syncope, CNA is a procedure associated with a significant reduction in syncope incidence and with low complication rates. Among the procedures used, both right and left ablation were more effective.

Telemonitoring use for uncontrolled hypertension management: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Within the context of uncontrolled blood pressure telemonitoring, the remote tracking of blood pressure and patient data, offers a transformative avenue. We aimed to perform a meta-analysis of the strategic redesign of healthcare services, harnessing information and communication technology (ICT) to enhance hypertension management and blood pressure control in primary care, providing timely interventions, and improving patient outcomes. METHODS: PubMed, Embase, and Cochrane databases were searched for RCTs comparing ICT with usual care in patients with uncontrolled hypertension. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: A total of twenty-eight studies and 13,111 patients were included, of whom 7,312 were randomized to ICT and 5,799 to usual care. Compared with standard care, ICT significantly reduced systolic blood pressure (MD -4.44 mmHg; 95% CI -5.55,-3.33; p<0.01) and diastolic blood pressure (MD -1.08 mmHg; 95% CI -1.71,-0.45; p<0.01). There was no significant difference between groups for adherence (RR 1.16; 95%CI 0.89-1.50; p=0.27). CONCLUSION: In this meta-analysis of RCTs of patients with uncontrolled hypertension, ICT was associated with a reduction in systolic and diastolic blood pressures, compared with usual care.

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.

Cardiovascular impact of cancer in patients with atrial fibrillation on direct oral anticoagulants: a systematic review and meta-analysis

BACKGROUND: The impact of cancer on patients with atrial fibrillation (AF) on direct oral anticoagulants (DOACs) remains a matter of debate. METHODS: We conducted a systematic review and meta-analysis exploring the effect of personal history of cancer in patients with AF on DOACs. PubMed, Embase, and Cochrane databases were searched for relevant studies. We used the random-effects model to calculate the risk ratio (RR) and 95% confidence intervals (CIs). Statistical analyses were performed using RStudio version 4.2.3. RESULTS: A total of six studies were included, with 63,177 patients. The mean age was 74.0 years. In this population of individuals who had AF and took DOACs, a history of cancer was associated with a significant increase in major bleeding (RR 1.72; 95% CI 1.24-2.38; p<0.01), gastrointestinal (GI) bleeding (RR 2.11; 95% CI 1.25-3.57; p<0.01), and any bleeding (RR 1.54; 95% CI 1.39-1.70; p<0.01). Additionally, all-cause death was significantly higher in patients with AF and a history of cancer (RR 1.93; 95% CI 1.35-2.76; p<0.01). There was no significant difference between groups in stroke (RR 1.77; 95% CI 0.66-4.73; p=0.25), cardiovascular (CV) death (RR 0.84; 95% CI 0.57-1.23; p=0.36), or myocardial infarction (MI) (RR 1.21; 95% CI 0.82-1.79; p=0.34). CONCLUSION: Our findings suggest that major bleeding, GI bleeding, any bleeding, and all-cause mortality significantly increased in patients with AF on DOACs who have a personal history of cancer, as compared with those who do not.

Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed or refractory multiple myeloma: a meta-analysis of randomized clinical trials

The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progressionfree survival (HR 0.52; 95% CI 0.43­0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63­0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26­1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02­1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38­2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13­1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms.

Long-term impact of home-based monitoring after an admission for acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials.

Background: Patients with heart failure have high rehospitalisation rates and poor cardiovascular outcomes. Home-based monitoring (HBM) has emerged with promising results in different settings. However, its long-term effects on patients recently admitted for acute decompensated heart failure (ADHF) remain uncertain. Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomised controlled trials (RCTs) comparing HBM with usual care (UC) that were published between database inception and June 24, 2023. We included studies with patients admitted for ADHF in the previous 6 months and with a minimum follow-up of 6 months. We excluded studies with patients hospitalised for reasons other than ADHF and studies with disproportional education interventions between arms. Statistical analyses were performed using R software version 4.3.2. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for categorical and continuous outcomes, respectively. Cochrane Collaboration's tool for assessing risk of bias in RCTs (RoB 2) was used to assess study quality. Publication bias was assessed via funnel plots and Egger's test, and heterogeneity was assessed through I2 statistics and sensitivity analysis. The protocol for this systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023465359). Findings: We included 16 RCTs comprising 4629 patients, of whom 2393 (51.7%) were randomised to HBM and 3150 (68%) were men. Follow-up ranged from six to fifteen months. As compared with UC, HBM significantly reduced all-cause mortality (RR 0.75; 95% CI 0.61, 0.91; p = 0.005), all-cause hospitalisations (RR 0.82; 95% CI 0.70, 0.97; p = 0.018), cardiovascular (CV) mortality (RR 0.53; 95% CI 0.36, 0.79; p = 0.002), hospitalisations for heart failure (RR 0.75; 95% CI 0.62, 0.91; p = 0.004), and CV hospitalisations (RR 0.72; 95% CI 0.55, 0.95; p = 0.018). There were no significant differences in length of hospital stay (MD 0.97 days; 95% CI -0.90, 2.84; p = 0.308). Interpretation: In patients recently admitted with ADHF, HBM significantly reduces long-term all-cause mortality and hospitalisations, CV mortality and hospitalisations, and hospitalisations for heart failure, as compared with UC. This supports the implementation of HBM as a standard practice to optimise patient outcomes following admissions for ADHF. However, future studies are warranted to evaluate the efficacy and safety of implementing HBM in the real-world setting. Funding: None.

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.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation on chronic hemodialysis: a meta-analysis of randomized controlled trials.

PURPOSE: Patients with atrial fibrillation (AF) and end-stage renal disease on chronic hemodialysis are at risk for thromboembolic and bleeding events. We aimed to perform a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in this population. METHODS: We systematically searched PubMed, Excerpta Medica Database (EMBASE) and Cochrane Library for randomized controlled trials (RCTs) comparing DOACs with VKAs in patients with AF on chronic hemodialysis from inception to February 2023 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes were reported using risk ratios (RRs) with 95% confidence intervals (CIs). Statistical analyses were performed using R version 4.2.2. RESULTS: We selected three RCTs including 341 patients, of whom 176 (51.6%) were randomized to DOACs. Follow-up ranged from 174 days to 3.38 years. There was no significant difference between groups in terms of cardiovascular mortality (RR 1.34; 95% CI 0.69-2.60; p = 0.39), all-cause mortality (RR 0.96; 95% CI 0.72-1.27; p = 0.77), ischemic/uncertain type of stroke or transient ischemic attack (RR 0.50; 95% CI 0.19-1.35; p = 0.17), or major or life-threatening bleeding (RR 0.70; 95% CI 0.39-1.25; p = 0.22). CONCLUSION: In this meta-analysis of three RCTs, no significant difference was observed between DOACs and VKAs in cardiovascular mortality, all-cause mortality, ischemic/uncertain type of stroke or transient ischemic attack, or major or life-threatening bleeding in patients with AF on chronic hemodialysis.

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.

PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Paclitaxel and carboplatin is the standard chemotherapy for the treatment of advanced or recurrent endometrial cancer. However, the benefit of adding programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors to chemotherapy is still unclear. METHOD: We searched PubMed, Scopus, Cochrane, and Web of Science databases for randomized controlled trials that investigated PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer. We computed hazard ratios (HRs) or risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses. RESULTS: A total of three studies and 1,431 patients were included. Compared with carboplatin plus paclitaxel-based chemotherapy, progression-free survival (PFS) rate (HR 0.32; 95% CI 0.23-0.44; p < 0.001) and overall survival (OS) at 30 months (RR 3.13; 95% CI 1.26-7.78; p = 0.01) were significant in favor of the PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel group in the mismatch repair-deficient subgroup. However, there were no significant differences in the mismatch repair-proficient subgroup for PFS (HR 0.74; 95% CI 0.50-1.08; p = 0.117) or OS at 30 months (RR 2.24; 95% CI 0.79-6.39; p = 0.13). CONCLUSION: Immunotherapy plus carboplatin-paclitaxel increased significantly PFS and OS among patients with advanced or recurrent endometrial cancer, with a significant benefit in the mismatch repair-deficient and high microsatellite instability population.

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.

Efficacy and safety of bexagliflozin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: To assess the efficacy of bexagliflozin in reducing glycated haemoglobin (HbA1c) and the occurrence of side effects in patients with type 2 diabetes (T2DM). METHODS: We searched the PubMed, Embase, Cochrane and ClinicalTrials.gov databases for placebo-controlled, randomized clinical trials published up until 15 February 2023. The primary outcome was change in HbA1c. We computed weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). RESULTS: A total of six studies and 3111 patients were included, of whom 1951 were prescribed bexagliflozin. Compared with placebo, bexagliflozin significantly reduced HbA1c levels (WMD -0.53%; 95% CI -0.75, -0.31), fasting plasma glucose levels (WMD -1.45 mmol/L; 95% CI -2.32, -0.57), systolic blood pressure (WMD -4.66 mmHg; 95% CI -6.41, -2.92), diastolic blood pressure (WMD -2.12 mmHg; 95% CI -3.94, -0.30), body weight overall (WMD -1.61 kg; 95% CI -2.14, -1.07), and body weight in patients with a body mass index >25 kg/m2 (WMD -2.05 kg; 95% CI -2.78, -1.31). The proportion of patients who achieved HbA1c < 7% was higher in patients who received bexagliflozin as compared with placebo (OR 1.94; 95% CI 1.36-2.78). There were no significant differences between groups regarding side effects such as hypoglycaemia, genital mycotic infection, urinary tract infection, diarrhoea, headache, nausea, polyuria, diabetic ketoacidosis, or all-cause mortality. CONCLUSIONS: In this meta-analysis, the use of bexagliflozin was associated with improved clinical and laboratory measures in patients with T2DM compared with placebo, with a similar profile of side effects. These findings support the efficacy of bexagliflozin in the treatment of T2DM.