Meta-analyses represent a key milestone in evidence-based medicine, integrating data from multiple studies to generate more robust estimates of an intervention's effects. By pooling information from various trials or observational studies, meta-analyses enhance statistical power, elucidate subgroup effects, and guide hypothesis generation. They have proven particularly useful in scenarios where individual randomized controlled trials (RCTs) cannot feasibly enroll enough participants (e.g., rare diseases or complex subpopulations) or when subgroups within an RCT are too small to draw meaningful conclusions. Nonetheless, meta-analyses carry intrinsic limitations, such as publication bias when performed using published data. Moreover, combining heterogeneous studies, or those of low quality, can yield spurious or conflicting results, as seen in early examples that overestimated benefits later disproven by large, well-conducted RCTs. Consequently, meta-analyses should be updated only when new evidence emerges that can refine or overturn existing conclusions. Beyond traditional methodologies, advanced techniques, such as individual patient data meta-analysis, network meta-analysis, dose-response meta-analysis, and umbrella reviews, offer additional granularity, enabling comparisons across multiple interventions or exposing nonlinear relationships between exposure and outcomes. Meanwhile, trial sequential analysis helps determine whether the accumulated evidence is conclusive or whether further studies are needed. When performed rigorously and interpreted cautiously, meta-analyses yield comprehensive insights that inform clinical practice and guide future research. Aim of this review is to define when a meta-analysis may be helpful in answering a clinical question.

Odontogenic Keratocystic (OKC) and Ameloblastoma (AB) are pathological entities characterized by aggressive behavior, slow growth, local invasiveness, and high recurrence rates. The aim of this systematic review with meta-analysis and trial sequential analysis (TSA) is to assess the prognostic role of extracting involved teeth during the surgical enucleation of OKCs and ABs in terms of recurrence risk.

A search was conducted in PubMed/Medline, Scopus, and Web of Science databases for studies reporting data on teeth extraction and recurrence rates. This systematic review was performed according to guidelines in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Meta-analysis was performed using the Mantel-Haenszel method with a random-effects model due to heterogeneity. The TSA was conducted to control and reduce for type I and II errors of statistical analysis.

Six studies were identified and analyzed qualitatively and quantitatively. A total of 737 lesions (674 OKCs and 64 ABs) were included, of which 508 had involved teeth. The meta-analysis included 451 OKCs; 367 lesions were treated with teeth extraction, and in 141 cases, the teeth were preserved. The overall Risk Ratio was 0.17 (95% CI: [0.04, 0.74]; P < .0001) for OKCs. Quantitative analysis could not be performed for ABs.

The analysis revealed that tooth extraction contextually to the enucleation of the lesion reduces the risk of recurrence by approximately 83% in the OKCs; this appears to have the same trend for ABs, but more evidence is needed.

In mechanically ventilated adult patients in the intensive care unit (ICU), selective decontamination of the digestive tract (SDD) has been shown to reduce the risk of infections and improve survival. While the benefits of SDD have been documented in this population, it remains unclear whether burn patients, who are at increased risk of infection and have distinct clinical characteristics, may experience similar benefits. In this systematic review we aimed to assess the desirable and undesirable patient-important effects of administering SDD to burn patients.

We conducted a systematic review with meta-analysis of randomized clinical trials (RCTs) assessing the effects of SDD versus placebo or no SDD in burn patients. The primary outcome was 30-day mortality. Secondary outcomes included serious adverse events, antimicrobial resistance, pneumonia, blood stream infections, ICU- and hospital-free days, and 90-day mortality. We searched all major databases and followed the recommendations provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The certainty of evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation approach.

We identified four RCTs with a total of 457 burn patients. All trials were assessed as having either 'some concerns' or 'high risk' of bias. The evidence was found to be very uncertain across all outcomes assessed. For mortality, the relative risk (RR) was 0.62 (95 % confidence interval (CI) 0.22-1.78, I2 = 75 %, random-effects model (REM), very low certainty evidence). For pneumonia, the RR was 0.75 (95 % CI 0.48-1.19, I2 = 0 %, fixed-effect model, very low certainty evidence). For bloodstream infections, the RR was 1.10 (95 % CI 0.71-1.69, I2 = 0 %, REM, very low certainty evidence). For hospital length of stay, the mean difference was -2.03 days (95 % CI -9.64-5.59, I2 = 51 %, REM, very low certainty evidence). We did not perform meta-analyses for the remaining secondary outcomes due to limited or no data. Trial sequential analysis could not be performed due to insufficient number of total participants and events in the included trials.

We found that the certainty of evidence is very low about the effects of SDD on patient-important outcomes in burn patients. Extrapolating from the evidence on mechanically ventilated adult ICU patients may be reasonable until more data from RCTs in burn patients emerge.

The best perioperative management of renin-angiotensin system inhibitors (RASi) in patients undergoing noncardiac surgery has been an ongoing debate as a result of inconclusive previous studies and insufficient data for robust guidelines. Although continuation of RASi may lead to intraoperative hypotension, withholding might also cause postoperative complications. Our meta-analysis aims to explore the postoperative outcomes of strategies of RASi management before surgery by evaluating randomised clinical trials, to provide more definitive conclusions for clinical practice.

We systematically searched PubMed, Scopus, Cochrane, and Web of Science until September 2024. Inclusion criteria included patients (≥18 yr) who underwent noncardiac surgery and received long-term RASi, which were either withheld or continued before surgery. Statistical analysis was conducted using R Studio version 4.4.2.

A total of seven RCTs with 8741 patients receiving long-term RASi before noncardiac surgery revealed no significant difference between continuation and withholding groups regarding cardiovascular complications (risk ratio [RR] 0.94, 95% confidence interval [CI] 0.80-1.09, P=0.41), mortality (RR 1.16, 95% CI 0.55-2.43, P=0.71), and acute kidney injury (RR 0.95, 95% CI 0.84-1.06, P=0.33). However, continuation of RASi was associated with a higher incidence of intraoperative hypotension (RR 1.33, 95% CI 1.23-1.44, P<0.001). Additionally, the incidence of postoperative severe hypertension (systolic BP >180 mm Hg) was significantly lower in the continuation group (RR 0.63, 95% CI 0.40-0.98, P<0.002).

Continuing RASi before noncardiac surgery does not significantly impact mortality, cardiovascular complications or the risk of acute kidney injury. However, continuation is associated with an increased risk of intraoperative hypotension, and withholding with a higher risk of postoperative severe hypertension.

CRD42024605208 (PROSPERO).

Autism spectrum disorder encompasses diverse patterns of social communication and repetitive, restricted behaviours. Various interventions have been developed to reduce the negative consequences of this disorder and improve levels of functioning, and recently interest in parent-mediated interventions has increased. Previous reviews and meta-analyses have investigated the effects of the parent-mediated interventions, however; a systematic review with meta-analysis of high quality has not been performed since 2013. This protocol for a systematic review with meta-analysis aims to describe the methods and purpose of synthesising current evidence regarding the effects (both positive and adverse) of parent-mediated interventions in both children with autism and their parents.

Electronic searches will be conducted in Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), American Psychological Association PsycInfo (PsycInfo) and Science Citation Index Expanded (SCI-EXPANDED). Randomised clinical trials of parent-mediated interventions for children with autism and control groups of usual care, waiting list or no treatment will be included. Two reviewers will independently screen, select and collect data. Methodological quality of included studies will be evaluated using Cochrane methodology. The primary outcome will be autism symptom severity as measured by the Autism Diagnostic Observation Schedule. Secondary outcomes will be adaptive functioning, adverse effects, child language, child´s quality of life, parental quality of life and parental stress. Meta-analyses and Trial Sequential Analysis will be performed.

This is the study protocol for a systematic review and meta-analysis of parent-mediated interventions versus usual care for children with ASD. Results of the review will inform clinicians and parents about the current evidence of the effects, both positive and negative, of parent-mediated interventions on younger children with autism and their parents, through improved methodology and inclusion of new studies. PROSPERO registration number: 385188.

Middle meningeal artery embolization (MMAE) has been studied as an adjunct to surgical evacuation for chronic subdural hematoma (cSDH). Previous meta-analyses comparing MMAE with conventional treatment for cSDH included both observational and randomized studies. To provide a more robust assessment, we performed a meta-analysis of randomized controlled trials to evaluate the outcomes of adjunct MMAE compared to surgical treatment alone.

We searched PubMed, EMBASE, and Cochrane CENTRAL databases for studies comparing adjunct middle meningeal artery embolization to surgical treatment alone until December 2024. The outcomes assessed were treatment failure, reoperation, complications, mortality, functional outcome, and length of hospital stay. Statistical analysis was performed via R software (version 4.3.2). Heterogeneity was assessed with I2 statistics. The risk of bias was assessed using the Cochrane Risk of Bias Tool for Randomized Trials.

We included 6 studies with 1,422 patients, of whom 700 (49.2 %) received adjunct middle meningeal artery embolization. The mean age ranged from 64.2 to 77.4 years in the embolization group and from 70 to 74.4 years in the surgery-only group. Among the patients, 435 (54.5 %) had previous known head trauma, and 315 (22.1 %) were on antiplatelets or anticoagulants. The follow-up ranged from 90 to 180 days. Adjunct middle meningeal artery embolization reduced the occurrence of treatment failure compared to surgical treatment alone (RR 0.482; 95 % CI 0.328 to 0.708; p < 0.001; I2 = 0 %) and reoperation (RR 0.333; 95 % CI 0.212 to 0.521; p < 0.001; I2 = 0 %), however, didńt reduce the occurrence of any cause mortality (RR 0.970; 95 % CI 0.400 to 2.353; p = 0.946; I2 = 39.6 %), functional dependence at the last follow-up (RR 1.000; 95 % CI 0.726 to 1.377; p = 0.705; I2 = 0 %), or the length of stay (MD 0.576; 95 % CI -0.085 to 1.238; p = 0.088; I2 = 0 %). Furthermore, no differences were found regarding complications secondary to the surgical procedure (RR 0.902; 95 % CI 0.688 to 1.182; p = 0.455; I2 = 0 %), and the occurrence of embolization-related complication was low (RR 0.013; 95 % CI 0.006 to 0.027; I2 = 0 %). Trial sequential analysis judged the sample size sufficient for treatment failure and reoperation but suggested that further trials are needed to prove differences in surgical-related complications.

Our results confirm that middle meningeal artery embolization significantly reduces recurrence and reoperation rates compared to surgery alone, with low adverse event rates. However, the impact on functional outcomes and mortality remains uncertain, warranting further studies to clarify its long-term benefits.

Although intraperitoneal local anesthetics are commonly used following intra-abdominal surgical procedures, the level of evidence supporting their use for postoperative pain management remains uncertain.

To evaluate the effect of intraperitoneal local anesthetics on postoperative pain following intra-abdominal surgery.

Medline (PubMed), Embase (Embase.com), CENTRAL, Web of science and ClinicalTrials.gov databases were searched from their inception to July 15th, 2022.

Randomized controlled trials comparing IPLA to placebo, usual care or other analgesic regimens among patients of any age undergoing any type of surgery.

Trial selection, data extraction, risk of bias assessment and the certainty of evidence were conducted in duplicate independently. Meta-analyses were performed using random effect models.

The co-primary outcomes were abdominal pain intensity at 6, 12, 24, 48, and 72 h after surgery. Secondary outcomes included postoperative nausea and vomiting, opioid use, recovery of gastrointestinal transit, length of hospital stay, postoperative chronic pain, persistent postoperative opioid use, quality of recovery and adverse events.

A total of 150 trials (n = 11,821 participants were included in our systematic review (97% of trials among adults). Intraperitoneal local anesthetics reduced postoperative pain intensity at 6 h (-0.86 point [95%CI -1.02 to -0.70]), 12 h (-0.74 point [95%CI -0.93 to -0.55]), 24 h (-0.65 point [95%CI -0.82 to -0.48]), and 48 h (-0.51 point [95%CI -0.70 to -0.31]), but not at 72 h (-0.38 point [95%CI -1.04 to 0.27]), with very low to low certainty of evidence. Modelled risk difference for achieving the clinically important effect and subgroup analyses among participants with moderate or high pain showed potential clinically significant effect from IPLA. Opioid use at 24 h (-10.4 mg of oral morphine equivalent [95% CI -13.1 to -7.6]), postoperative nausea and vomiting (RR 0.79 [95% CI -0.71 to 0.88]), and time to gastrointestinal transit recovery (-3.80 h [95% CI -7.54 to -0.07]) were also reduced. We found no association for other outcomes.

Intraperitoneal local anesthetics may be associated with a small analgesic effect following intra-abdominal surgery. Considering the low to very low level of evidence supporting these findings, along with the limited data on adverse effects and long-term outcomes, their adoption as a standard of care intervention cannot be recommended at this stage.

CRD42018115062.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects (i.e. benefits and harms) of psychological therapies for post-traumatic stress disorder and complex post-traumatic stress disorder in children and adolescents.

Recent studies have reported that endovascular thrombectomy (ET) may improve neurological outcomes in large-core stroke.We performed a systematic review and meta-analysis to compare the pooled efficacy and safety of ET and of the best medical treatment among patients with large-core stroke.We searched the PubMed/MEDLINE, Scopus, and Cochrane databases from inception to November 2023. The inclusion criteria were randomized controlled trials (RCTs) comparing ET and the best medical treatment available among patients with large-core stroke (Alberta Stroke Program Early Computed Tomography Score [ASPECTS] < 6 or ischemic core > 50 mL on perfusion imaging) within 24 hours of symptom onset.We included 6 RTCs comprising 1,887 patients (ET group: n = 945). Endovascular thrombectomy was associated with good neurological outcomes (odds ratio [OR]: 2.92; 95% confidence interval [95%CI]: 2.17-3.93), or independent walking (OR: 2.22; 95%CI: 1.72-2.86). Trial sequential analysis confirmed a robust statistical significance for good neurological outcomes favoring ET. Endovascular thrombectomy was associated with higher risks of developing intracranial bleeding (OR: 2.65; 95%CI: 1.35-5.22) and symptomatic intracranial bleeding (OR: 1.83; 95%CI: 1.14-2.94). There were no differences between the groups regarding mortality or decompressive craniectomy. Patients submitted to non-contrast computed tomography (CT) with CT angiography (CTA) scans were analyzed separately and showed good neurological outcomes, comparable to those of the patients submitted to other imaging modalities (OR: 3.24; 95%CI: 1.52-6.92).Endovascular thrombectomy was associated with good neurological outcomes and independent walking in patients with large-core acute ischemic stroke. However, it was also associated with an increased risk of developing intracranial bleeding. Non-contrast head CT with CTA scans may be appropriate for screening patients to undergo ET.

The superiority of radical antegrade modular pancreatosplenectomy versus standard distal pancreatectomy has never been demonstrated.

A systematic review was performed to identify all comparative studies about radical antegrade modular pancreatosplenectomy versus standard distal pancreatectomy. Random-effects analysis was performed, and hazard ratios, odds ratios, and mean differences were calculated. Using trial sequential analysis, type I and II errors were evaluated by comparing the accrued sample size with the required sample size. When the required sample size is superior to the accrued sample size, type I or II errors can be hypothesized. The critical endpoint was overall survival. Secondary endpoints were disease-free survival, R0 resection rate, major morbidity and mortality rate, clinically relevant postoperative pancreatic fistula, delayed gastric emptying, postpancreatectomy hemorrhage, length of stay, and operative time.

The accrued sample size and required sample size were 1,172 and 176 for the primary endpoint, respectively. The overall survival was similar between the 2 groups, with a hazard ratio of 1.33 (95% confidence interval: 0.89-2.00). The required sample size reached, and false-negative equivalence can be excluded. Disease-free survival, R0 resection rate, major morbidity and mortality rate, clinically relevant postoperative pancreatic fistula, delayed gastric emptying, postpancreatectomy hemorrhage, and operative time are similar and reached required sample sizes, suggesting that false equivalence can be excluded. Length of stay was shorter in radical antegrade modular pancreatosplenectomy than in standard distal pancreatectomy (-3.48 days; -6.66 to -0.31 days). The accrued sample size was 826, and the required sample size was not reached. False-positive results cannot be excluded.

Radical antegrade modular pancreatosplenectomy was not superior in guaranteeing a better overall survival and disease-free survival. The data are robust, and further retrospective comparative studies are unnecessary.

Increasing evidence connects gallstone disease (GSD) to all types of cancer incidence; however, the results were inconsistent. The present study aimed to evaluate whether and to what extent these associations exist comprehensively.

We systematically searched published longitudinal studies indexed in PubMed and Embase database from dates of inception to March 31, 2020. We pooled the effect of GSD on all-cause cancer incidence. Moreover, we further employed stratified analysis concerning sex, geographic background, surgery status, and follow-up period. Trial sequential analysis (TSA) was applied to decide whether the included sample size was sufficient for evaluating these associations.

Fifty-one studies incorporating over 13 million participants were eligible for analysis in this study. GSD pose an increased risk of all-cause cancer risk (pooled RR = 1.43; 95% CI: 1.33-1.54) compared with the healthy controls, especially hematologic malignancy (pooled RR = 1.14; 95% CI: 1.05-1.25), gastrointestinal cancers (pooled RR = 1.28; 95% CI: 1.15-1.41), liver, pancreas, and biliary tract cancer (pooled RR = 1.84; 95% CI: 1.62-2.10), and kidney cancer (pooled RR = 1.19; 95% CI: 1.03-1.37). These associations are not markedly changed after stratification by different subgroups. Moreover, the TSA confirmed the sample size was sufficient to draw these conclusive conclusions.

The present meta-analysis with sufficient evidence indicates GSD increases the risk for all causes of cancer incidence. The evidence may warrant GSD patients to perform screening and prophylactic treatment for the prevention of these complications. The indication for cholecystectomy should be determined through a comprehensive evaluation of the patient's clinical presentation, with a thorough assessment of the potential therapeutic benefits and surgical risks.

Introduction: The analysis of postoperative pain has gained prominence as an important outcome following inguinal hernia repair (IHR), and various strategies have been employed. However, the use of erector spinae plane block (ESPB) in IHR is debated. Therefore, this systematic review and meta-analysis evaluates their efficacy. Methods: We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled trials (RCTs), comparing the impact of ESPB on pain outcomes following IHR. Outcomes included pain using the visual analog scale (VAS) at 2, 6, 12, and 24 hours after surgery and postoperative nausea and vomiting (PONV) rates. Statistical analyses were performed using R software and trial sequential analysis. Results: We included three RCTs comprising 145 patients, of which 66 (45.5%) were submitted to ESPB. Between the included studies, two analyzed minimally invasive IHR, while one analyzed the open Lichtenstein technique. We found no differences in VAS pain scores at 2 hours (MD: -0.56; 95% CI: [-3.53; 2.42]; P = .71) and at 6 hours (MD: -1.13; 95% CI: [-2.50; 0.23]; P = .1) postoperatively. Also, no clinically or statistically significant differences were found in the VAS score for ESPB at 12 hours (MD: -0.96; 95% CI: [-1.94; -.02]; P = .051) and 24 hours postoperatively (MD: -0.19; 95% CI: [-0.53; .15]; P = .28). No statistically significant differences were found in PONV rates between the groups (7.6% versus 20.3%; RR 0.38; 95% CI: [0.14; 1.0]; P = .05). Conclusion: This meta-analysis found no differences in postoperative pain scores or PONV between the ESPB and control groups. Further studies are necessary to better understand the role of ESPB in inguinal hernia repair.

Sophorae flavescentis (kushen) preparations are widely used to control malignant pleural effusion (MPE) through intrapleural perfusion.

This analysis aims to verify the therapeutic values of perfusion with kushen preparations for controlling MPE, reveal the optimal treatment plan, suitable population, and usage, and to demonstrate their clinical effectiveness and safety.

We performed and reported this systematic review/meta-analysis (PROSPERO: CRD42023430139) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All randomized controlled trials (RCTs) concerning perfusion with kushen preparation for MPE were collected from Chinese and English databases. We clustered all eligible studies into multiple homogeneous treatment units, assessed their methodological quality using a RoB 2, pooled the data from each unit, and summarized the quality of the evidence.

We included 83 RCTs reporting three types of kushen preparation: compound kushen injection (CKI), kang'ai injection, and matrine injection. All trials were clustered into perfusion with CKI alone or with the addition of sclerosants, kang'ai, or matrine-plus platinum for controlling MPE. Compared with cisplatin alone, perfusion with CKI alone displayed a similar complete response, pleurodesis failure, and pleural progression (odds ratios =1.10, 95% CI 0.76 to 1.60; 0.80, 0.56 to 1.14; 0.63, 0.33 to 1.21). Of 14 homogeneous treatment plans, perfusion with CKI and cisplatin significantly improved the complete response (2.71, 2.30 to 3.19) and showed low pleurodesis failure (0.26, 0.22 to 0.32), pleural progression (0.22, 0.14 to 0.36), myelosuppression (0.34, 0.24 to 0.47), neutropenia (0.35, 0.26 to 0.46), gastrointestinal reaction (0.36, 0.29 to 0.44), hepatorenal toxicity (0.42, 0.28 to 0.63 and 0.32, 0.24 to 0.44), and fever (0.50, 0.30 to 0.82). These results were moderate quality (⊕⊕⊕Ο) supported by firm or conclusive information. Additionally, perfusion with kang'ai or matrine and cisplatin also improved the complete response (3.04, 1.76 to 5.26 and 1.87, 1.26 to 2.78) and displayed low pleurodesis failure (0.23, 0.14 to 0.41 and 0.27, 0.17 to 0.44). The results were moderate to low quality (⊕⊕⊕Ο to ⊕⊕ΟΟ).

Current moderate evidence demonstrates that CKI may be an effective palliative intervention for MPE which, combined with cisplatin, may be an optimal treatment plan. Kang'ai or matrine may be other potential choices.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42023430139.

Chronic hepatitis B is a major worldwide public health concern. Entecavir, one nucleos(t)ide analogue antiviral therapy option, is recommended as the first-line drug for chronic hepatitis B in many clinical guidelines. However, none of the guideline recommendations are based on the findings of a systematic review with meta-analysis, where entecavir versus no treatment or placebo are compared directly.

To evaluate the benefits and harms of entecavir versus no treatment or placebo in children and adults with chronic hepatitis B, who are either hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative.

We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, three other databases, online trial registries, and reference lists, and contacted authors. The latest search was on 19 July 2024.

We included randomised clinical trials comparing entecavir versus no treatment or placebo in children or adults, or both, with chronic hepatitis B, and irrespective of treatment history with other antiviral drugs and other viral co-infections. We allowed co-interventions when administered equally to all intervention groups.

The outcomes reported in this abstract and in the summary of findings table are all-cause mortality, health-related quality of life, and proportion of people with serious adverse events at the longest follow-up.

We used the Cochrane RoB 2 tool to assess risk of bias in the included trials.

We used a random-effects model to meta-analyse outcome results, where possible, and presented the results as a risk ratio (RR) with 95% confidence interval (CI). Where there was considerable heterogeneity, we performed a narrative analysis. We used a fixed-effect model for sensitivity analysis. We used GRADE to evaluate the certainty of evidence.

We included 22 randomised clinical trials (published from 2005 to 2022) with 2940 participants diagnosed with chronic hepatitis B. All trials had a parallel-group design. The experimental intervention was oral entecavir, with a follow-up duration of 5 weeks to 228 weeks. The comparator in 12 trials was no treatment, and in 10 trials was placebo. Fourteen trials equally administered co-interventions to the trial participants in the entecavir and no treatment and placebo groups. One trial included participants between 14 years and 55 years of age, one trial included only children, 19 trials included only adults, and one trial did not provide the age of participants.

Twenty trials contributed data to the quantitative analysis. Ten trials (1379 participants) reported all-cause mortality with a mean follow-up duration of 48.9 weeks (range 5 to 100 weeks). The result was not estimable because no deaths occurred in any of the entecavir and no treatment or placebo groups. None of the trials provided data on health-related quality of life. We are very uncertain about the effect of entecavir versus no treatment or placebo on the proportion of people with serious adverse events (RR 0.66, 95% CI 0.33 to 1.32; absolute risk difference 22 fewer per 1000 (from 44 fewer to 21 more); 15 trials, 1676 participants; very low-certainty evidence). The mean follow-up duration was 58.4 weeks (range 5 weeks to 228 weeks). We downgraded the certainty of evidence for these outcomes to very low, mainly because the overall risk of bias in most trials was with some concerns or high, and serious imprecision (no events or few events).

Given the issues of risk of bias and insufficient power of the included trials and the very low certainty of the available evidence, we could not determine the effect of entecavir versus no treatment or placebo on critical outcomes such as all-cause mortality and serious adverse events. There is a lack of data on health-related quality of life. Given the first-line recommendation and wide usage of entecavir in people with chronic hepatitis B, further evidence on clinically important outcomes, analysed in this review, is needed.

This Cochrane review had no dedicated funding.

Registration: Entecavir for children and adults with chronic hepatitis B, CD015536 via DOI 10.1002/14651858.CD015536.

Trial sequential methods have been introduced to address issues related to increased likelihood of incorrectly rejecting the null hypothesis in meta-analyses due to repeated significance testing. Between-study variance (τ2) and its estimate ( τ ^ 2) play a crucial role in both meta-analysis and trial sequential analysis with the random-effects model. Therefore, we investigated how different τ ^ 2 impact the results of and quantities used in trial sequential analysis.

This case study was grounded in a Cochrane review that provides data for smaller (< 10 randomized clinical trials, RCTs) and larger (> 20 RCTs) meta-analyses. The review compared various outcomes between video-laryngoscopy and direct laryngoscopy for tracheal intubation, and we used outcomes including hypoxemia and failed intubation, stratified by difficulty, expertise, and obesity. We calculated odds ratios using inverse variance method with six estimators for τ2, including DerSimonian-Laird, restricted maximum-likelihood, Paule-Mandel, maximum-likelihood, Sidik-Jonkman, and Hunter-Schmidt. Then we depicted the relationships between τ ^ 2 and quantities in trial sequential analysis including diversity, adjustment factor, required information size (RIS), and α-spending boundaries.

We found that diversity increases logarithmically with τ ^ 2, and that the adjustment factor, RIS, and α-spending boundaries increase linearly with τ ^ 2. Also, the conclusions of trial sequential analysis can differ depending on the estimator used for between-study variance.

This study highlights the importance of τ ^ 2 in trial sequential analysis and underscores the need to align the meta-analysis and the trial sequential analysis by choosing estimators to avoid introducing biases and discrepancies in effect size estimates and uncertainty assessments.

Cardiovascular diseases remain the leading cause of mortality worldwide. Tirzepatide is approved for the treatment of type 2 diabetes mellitus and overweight and is increasingly used. The adverse effects with tirzepatide may not be disease-specific and have not been assessed previously.

We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S)) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in January 2025. Two review authors will independently extract data and perform risk of bias assessments. We will include randomised clinical trials comparing tirzepatide versus placebo or no intervention in all patient groups with an increased risk of cardiovascular events. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be myocardial infarction, stroke, all-cause hospitalisation and non-serious adverse events. Data will be synthesised by meta-analyses and Trial Sequential Analysis, risk of bias will be assessed with the Cochrane Risk of Bias tool-version 2. We will systematically assess if the thresholds for statistical and clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations.

This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.

CRD42024599035.

Middle meningeal artery embolization (MMAE) has gained attention as an innovative approach for chronic subdural hematoma (cSDH). It can be utilized either as a standalone treatment or as an adjunct to surgical evacuation, with the primary goal of reducing the risk of cSDH recurrence. Therefore, we aim to investigate the efficacy and safety of MMAE in cSDH patients. Databases were systematically searched for randomized controlled trials (RCTs) reporting the use of MMAE in cSDH patients. All statistical analyses were performed using Review Manager 5.4.1. We employed risk ratio (RR) and Mean Differences (MD) with 95% confidence intervals (CIs) as the measure of effect size using a random-effects model. We included seven RCTs (1,623 patients; mean age, 72.7 ± 10.9 [MMAE group] and 72.3 ± 11.0 [usual-care group] years; 74.9% [MMAE] and 77.3% [usual-care] were male). MMAE significantly reduced recurrence (RR 0.47, 95% CI: 0.34 to 0.65, p < 0.001). No statistically significant differences were observed in good (RR 1.01, 95% CI: 0.97 to 1.05, p = 0.77) and favorable functional outcome (RR 1.01, 95% CI: 0.96 to 1.07, p = 0.69). Hematoma volume was only significantly reduced in the adjunctive MMAE subgroup analysis (MD -6.49, 95% CI: -12.21 to -0.78, p = 0.03). No statistically significant differences were observed in adverse events (RR 0.97, 95% CI: 0.68 to 1.39, p = 0.885), serious adverse events (RR 0.78, 95% CI: 0.59 to 1.04, p = 0.09), and mortality (RR 0.98, 95% CI: 0.42 to 2.30, p = 0.97). MMAE significantly reduced recurrence risk compared to usual care, with benefits observed in adjunctive MMAE, including lower reoperation rates and reduced hematoma volume at 90 days. Functional outcomes at 90 days were not significantly different between groups. Similarly, adverse events and mortality rates were comparable between groups Clinical trial number: Not applicable.

Randomized controlled trials comparing transcatheter aortic valve implantation with surgical aortic valve replacement demonstrate conflicting evidence, particularly in low-risk patients. We aim to reevaluate the evidence using trial sequential analysis, balancing type I and II errors, and compare with conventional meta-analysis.

Databases were searched for randomized controlled trials, which were divided into higher-risk and lower-risk randomized controlled trials according to a pragmatic risk classification. Primary outcomes were death and a composite end point of death or disabling stroke assessed at 1 year and maximum follow-up. Conventional meta-analysis and trial sequential analysis were performed, and the required information size was calculated considering a type I error of 5% and a power of 90%.

Eight randomized controlled trials (n = 5274 higher-risk and 3661 lower-risk patients) were included. Higher-risk trials showed no significant reduction in death at 1 year with transcatheter aortic valve implantation (relative risk, 0.93, 95% CI, 0.81-1.08, P = .345). Lower-risk trials suggested lower death risk on conventional meta-analysis (relative risk, 0.67, 95% CI, 0.47-0.96, P = .031), but trial sequential analysis indicated potential spurious evidence (P = .116), necessitating more data for conclusive benefit (required information size = 5944 [59.8%]). For death or disabling stroke at 1 year, higher-risk trials lacked evidence (relative risk, 0.90, 95% CI, 0.79-1.02, P = .108). In lower-risk trials, transcatheter aortic valve implantation indicated lower risk in conventional meta-analysis (relative risk, 0.68, 95% CI, 0.50-0.93, P = .014), but trial sequential analysis suggested potential spurious evidence (P = .053), necessitating more data for conclusive benefit (required information size = 5122 [69.4%]). Follow-up results provided inconclusive evidence for both primary outcomes across risk categories.

Conventional meta-analysis methods may have prematurely declared an early reduction of negative outcomes after transcatheter aortic valve implantation when compared with surgical aortic valve replacement.

Surgery is the first-line curative treatment for most solid-organ malignancies. During major surgeries, fluid under- or over administration can have a significant impact on recovery and postoperative outcomes. For patients undergoing oncologic surgery, delayed recovery or complications could additionally impact subsequent oncologic treatment planning. This systematic review and meta-analysis aims to evaluate the impact of goal-directed fluid therapy (GDFT) on perioperative outcomes after oncologic surgeries.

We systematically searched PubMed, EMBASE, CINAHL, and Web of Science citation index for clinical trials comparing the GDFT to routine clinical care. The primary outcomes of interest are the hospital length of stay and the total incidence of postoperative complications. Secondary outcomes include organ-specific complications and recovery of bowel function.

The literature search was last updated on February 17, 2024. We identified a total of 24 randomized controlled trials (RCTs) comparing GDFT to routine care with 1172 and 1186 patients, respectively. The GDFT arm had a significantly shorter length of hospital stay (mean difference [MD], 1.57 days, 95% confidence interval [CI], -2.29 to -0.85, P < .01), as well as lower incidence of complications (risk ratio, 0.74, 95% CI, 0.56-0.97, P = .03). The GDFT arm also had a shorter time to bowel function recovery (MD, 0.58 days, 95% CI, -1.02 to -0.14, P = .01). None of the included trials reported the longer-term oncologic outcomes. The overall certainty of evidence is low due to between-study variance and study risk of bias. Trial sequence analysis indicates that further studies are unlikely to alter the conclusion regarding postoperative length of stay but may provide further information on the postoperative complications.

Our systematic review and meta-analysis suggests that in oncologic surgery, intraoperative GDFT significantly reduces the length of hospital stay, lowers the risk of complications, and facilitates bowel function recovery. Further studies are required to evaluate whether the improvement in early postoperative outcomes leads to better long-term oncologic outcomes.

The decision to continue aspirin before elective coronary artery bypass graft surgery remains contentious because of competing thrombotic and bleeding risks. We performed a contemporary systematic review and meta-analysis to compare outcomes between patients undergoing coronary artery bypass grafting who stopped and continued aspirin before surgery.

PubMed, MEDLINE, and CENTRAL databases were searched from inception to 4 October 2023 for randomized controlled trials comparing patients undergoing coronary artery bypass grafting who continued preoperative aspirin with those who discontinued before surgery. Studies with cointervention arms and multivariable-adjusted or propensity matched observational studies were excluded. Summary odds ratios were calculated using a random effects model for dichotomous and continuous variables. Subgroup and sensitivity analyses were conducted in order to explore sources of heterogeneity.

Fifteen eligible randomized controlled trials were included with a total of 6,188 patients. Patients who continued aspirin demonstrated no significant difference in all-cause mortality (odds ratio, 1.37; confidence interval, 0.81-2.33), perioperative myocardial infarction (odds ratio, 0.81; confidence interval, 0.55-1.18), and postoperative blood loss (mean difference, 66.12 mL; confidence interval, -1.45 to 133.69). No significant difference was observed between low-dose and greater doses of aspirin. There was minimal heterogeneity amongst included studies (I2 = 0%, P = .97, I2 = 33%, P = .13, and I2= 76, P = .06, respectively). Studies were of low methodologic quality according to Cochrane Risk of Bias for Randomized Trials.

This largest to-date systematic review and meta-analysis found no significant difference for risk of all-cause mortality, perioperative myocardial infarction, and postoperative bleeding between patients continuing and stopping aspirin before coronary artery bypass grafting.

We aimed to reevaluate randomized controlled trial data on outcomes of cerebral embolic protection device use during transcatheter aortic valve implantation. A conventional meta-analysis followed by trial sequential analysis was conducted to evaluate the strength of the current evidence.

Databases were searched for randomized controlled trials. Primary outcomes included all stroke, disabling stroke, and all-cause mortality. Conventional study-level meta-analysis was performed using random-effects modeling. Trial sequential analysis was conducted to generate adjusted significance boundaries, futility boundaries, and the required information size considering a type I error of 5% and a power of 90%. Seven trials were included with a total of 4031 patients, of whom 2171 were treated with a device and 1860 were not. Conventional meta-analysis showed no significant difference in all stroke (relative risk [RR], 0.85 [95% CI, 0.61-1.18]; P=0.339) and disabling stroke (RR, 0.59 [95% CI, 0.30-1.13]; P=0.113) with device use. The trial sequential analysis determined an absence of evidence for all stroke (required information size of 71 650 [5.6%]) and disabling stroke (required information size of 337 256 [1.2%]). Conventional meta-analysis determined no significant difference in all-cause mortality (RR, 1.03 [95% CI, 0.49-2.17]; P=0.928) with device use. The trial sequential analysis determined that the futility boundary was reached (required information size of 5772 [69.3%]).

There are insufficient randomized controlled trial data on cerebral embolic protection device use to provide conclusive meta-analytic findings for stroke outcomes.

Tenofovir alafenamide (TAF) is widely used for chronic hepatitis B (CHB) treatment due to its improved renal and bone safety compared to tenofovir disoproxil fumarate (TDF). However, emerging evidence suggests that TAF may adversely affect lipid metabolism, raising concerns about potential cardiovascular risks. A systematic review and meta-analysis following PRISMA guidelines was conducted. Studies comparing lipid profile changes in CHB patients receiving TAF, TDF, or entecavir (ETV) were retrieved from PubMed, Cochrane, and Embase. Primary outcomes included changes in total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Sensitivity analyses were performed to assess potential confounders, including lipid-lowering therapy. Trial sequential analysis (TSA) was used to evaluate the sufficiency of evidence. A total of 23 studies (5 RCTs, 18 observational) were included. Observational data showed significant increases in TC (MD = 10.74 mg/dL), TG (MD = 11.56 mg/dL), LDL (MD = 3.08 mg/dL), and HDL (MD = 7.51 mg/dL) with TAF versus TDF. Meta-analysis of RCTs confirmed these findings, showing TC (MD = 18.28 mg/dL), LDL (MD = 13.09 mg/dL), and HDL (MD = 4.95 mg/dL) elevations. TAF is associated with increased lipid levels, likely due to the loss of TDF's lipid-lowering effect. While its cardiovascular risk remains uncertain, clinicians should monitor lipid profiles in CHB patients on TAF, particularly those at high cardiovascular risk.

Postoperative pain remains a major problem across a wide range of surgical procedures. The efficacy and clinical utility of the Erector Spinae Plane Block (ESPB) in reducing postoperative pain remains uncertain.

To evaluate the efficacy and safety of the ESPB compared with placebo or sham block in perioperative pain management.

We searched PubMed, Embase, Web of Science, Scopus, and Cochrane CENTRAL for randomized controlled trials (RCTs) comparing ESPB to placebo or sham block in surgical patients. Primary outcomes included postoperative pain at 2 h, 6 h, 24 h, and 48 h, intraoperative and cumulative postoperative opioid consumption (24 h), and postoperative nausea and vomiting, pruritus, and block-related adverse events. Subgroup and sensitivity analyses, as well as meta-regressions, were performed to explore sources of heterogeneity. Trial sequential analysis (TSA) was used to assess the quantitative robustness of the available data. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42024583633.

Forty-three RCTs were included, with 1361 patients randomized to the Erector Spinae Plane Block group. ESPB reduced postoperative pain at 2 h (MD -1.46;95 % CI -1.98 to -0.94;p < 0.001;I2 = 91 %), 6 h (MD -1.23;95 % CI -1.64 to -0.83;p < 0.001;I2 = 89 %), 24 h (MD -0.47;95 % CI -0.67 to -0.28;p < 0.001;I2 = 78 %), and 48 h (MD -0.24;95 % CI -0.39 to -0.09;p = 0.002;I2 = 10 %). Also, intraoperative opioid consumption (MD -137.43 μg;95 % CI -208.73 to -66.13;p < 0.001;I2 = 100 %), 24 h cumulative opioid consumption (MD -25.62 mg;95 % CI -31.31 to -19.93;p < 0.001;I2 = 99 %), and incidence of postoperative nausea and vomiting (RR 0.56;95 % CI 0.44 to 0.72;p < 0.001;I2 = 16 %) were significantly lower in patients submitted to ESPB. No significant differences were found in postoperative pruritus (RR 0.62;95 % CI 0.35 to 1.10;p = 0.105;I2 = 27 %). Notably, no block-related adverse events were reported in any study. Certainty of evidence was rated as low to moderate for most outcomes. TSA suggested that no further trials are needed to assess ESPB efficacy in the analyzed outcomes, except for postoperative pruritus.

ESPB is a safe and effective regional anesthesia technique that significantly reduces postoperative pain and opioid consumption across various surgical procedures.

This study aims to conduct a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of auricular acupoint therapy (AAT) for functional gastrointestinal disorders (FGIDs).

We conducted a thorough search across eight databases, including PubMed, EMBASE, Web of Science, the Cochrane Library, CNKI, Wanfang, VIP, and CBM. The search covered the period from the inception of each database up to June 30, 2024. The authors independently reviewed all the references, evaluated the risk of bias, and extracted the data. GRADEpro software was utilized to calculate overall strength of evidence. A random effects or fixed effects model was selected on the basis of the p-value and I2 . RevMan 5.3, Stata/MP 18.0, R 4.3.1 and R Studio 2023.09.0 were used for data processing. TSA 0.9.5.10 beta software was used to evaluate data stability.

The review included 19 randomized controlled trials with a total of 1,681 patients (895 in the treatment group and 886 in the control group). The treatment duration ranged from 2-12 weeks. The meta-analysis revealed that, compared with the control, AAT was significantly more effective at treating FGIDs (RR: 1.35; 95% CI: 1.21-1.51; p < 0.001), reducing the symptom score (MD: -1.94; 95% CI: -3.06 to -0.85; p < 0.001; five trials), improving the SAS score (MD: -12.47; 95% CI: -13.92 to -11.01; p < 0.001; five trials), and improving the SDS score (MD: -4.97; 95% CI: -9.23 to -0.72; p = 0.02; six trials). A total of two articles mentioned relatively significant adverse reactions (MD: 2.98; 95% CI: 0.51-17.26; p = 0.009). Sensitivity and trial sequential analyses confirmed the stability of these results.

While our meta-analysis suggests that AAT may offer benefits for FGIDs, these results must be interpreted with caution due to methodological limitations in the included trials. Further investigations in high-quality trials are warranted.

https://clinicaltrials.gov/, identifier CRD42024558786.

Systematic reviews and meta-analyses are essential tools for synthesizing evidence from multiple studies. Recently, trial sequential analyses (TSAs) have gained popularity as a component of meta-analyses, helping researchers dynamically monitor evidence as new studies are incorporated. This article introduces a meta-epidemiological study aimed at evaluating the reproducibility of TSAs within systematic reviews published in 2023. Two independent investigators assessed and reproduced the main TSA for each included systematic review. Our search in PubMed yielded a convenience sample of 98 systematic reviews. Only 28% (27/98) of the included TSAs provided sufficient data to calculate the required information size, an essential element for assessing statistical power and conducting TSAs. Among these, 81% (22/27) provided the necessary data to determine decision boundaries and Z-curves in TSAs. Overall, full reproducibility was achieved for only 13% (13/98) of TSAs. Specifically, for binary outcomes, 65% (47/72) of TSAs failed to report event rates in control groups, and 44% (32/72) did not report relative risk reductions. For continuous outcomes, 53% (17/32) failed to report minimally relevant differences, and 72% (23/32) did not report variances. These elements are crucial for TSA reproducibility. Moreover, the reproducibility of TSAs was associated with journal impact factors and adherence to the PRISMA guidelines. A collective effort is needed from systematic review authors, peer reviewers, and journal editors to improve the reproducibility of TSAs.

A meta-analysis is a quantitative, formal study design in epidemiology and clinical medicine that systematically integrates and quantitatively synthesizes findings from multiple independent studies. This approach not only enhances statistical power but also enables the exploration of effects across diverse populations and helps resolve controversies arising from conflicting studies.

This study aims to develop and implement a user-friendly tool for conducting meta-analyses, addressing the need for an accessible platform that simplifies the complex statistical procedures required for evidence synthesis while maintaining methodological rigor.

The platform available at MetaAnalysisOnline.com enables comprehensive meta-analyses through an intuitive web interface, requiring no programming expertise or command-line operations. The system accommodates diverse data types including binary (total and event numbers), continuous (mean and SD), and time-to-event data (hazard rates with CIs), while implementing both fixed-effect and random-effect models using established statistical approaches such as DerSimonian-Laird, Mantel-Haenszel, and inverse variance methods for effect size estimation and heterogeneity assessment.

In addition to statistical tests, graphical representations including the forest plot, the funnel plot, and the z score plot can be drawn. A forest plot is highly effective in illustrating heterogeneity and pooled results. The risk of publication bias can be revealed by a funnel plot. A z score plot provides a visual assessment of whether more research is needed to establish a reliable conclusion. All the discussed models and visualization options are integrated into the registration-free web-based portal. Leveraging MetaAnalysisOnline.com's capabilities, we examined treatment-related adverse events in patients with cancer receiving perioperative anti-PD-1 immunotherapy through a systematic review encompassing 10 studies with 8099 total participants. Meta-analysis revealed that anti-PD-1 therapy doubled the risk of adverse events (risk ratio 2.15, 95% CI 1.39-3.32), with significant between-study heterogeneity (I2=95%) and publication bias detected through the Egger test (P=.02). While these findings suggest increased toxicity associated with anti-PD-1 treatment, the z score analysis indicated that additional studies are needed for definitive conclusions.

In summary, the web-based tool aims to bridge the void for clinical and life science researchers by offering a user-friendly alternative for the swift and reproducible meta-analysis of clinical and epidemiological trials.

Trial sequential analysis (TSA) is an increasingly used tool in systematic reviews to monitor synthesized evidence. However, the current practice of TSAs often overlooks the order of same-year studies, which are typically ordered alphabetically based on the last names of the studies' authors by default in the widely used TSA software application. This practice is inappropriate and contrary to the TSA's definition. This issue is particularly concerning in systematic reviews on time-sensitive topics, such as COVID-19, where reviews include many studies within a short period. In this article, we use a case study to illustrate the impact of the order of same-year studies on TSA conclusions. It shows dramatically different patterns of evidence accumulation when same-year studies are ordered alphabetically vs in their actual temporal order. This article offers suggestions for authors to pay attention to study ordering in future TSAs.

Schizophrenia and bipolar disorder are understood to have neuroinflammatory/neuro-immunological basis in their etiopathogenesis. There are few studies synthesizing the association of schizophrenia and bipolar disorder in type 1 diabetes mellitus (T1DM), a common immunological disorder.

We performed meta-analyses of studies assessing the prevalence and risk of schizophrenia and related disorders and bipolar disorder in individuals with T1DM. Fifteen studies consisting of a total sample of 9,768,028 (T1DM: 435,553; non-T1DM controls: 9,332,475) were included. Random-effects meta-analyses using the restricted maximum likelihood method for pooling logit transformed prevalence values and the Mantel-Haenszel test for pooling risk ratios were used. I 2 statistic and the rank correlation test for Funnel plots' asymmetry were used to assess heterogeneity and publication bias, respectively.

Pooled (transformed-back-transformed) prevalence for schizophrenia and related psychotic disorders was 0.37% (95%CI: 0.19-0.73), and for bipolar disorder it was 0.39% (95%CI: 0.05-2.99) (together: 0.38% (95%CI: 0.2-0.71)] in T1DM. The prevalence models showed significant heterogeneity but were statistically significant, had low publication bias, and survived sensitivity analysis. The pooled risk ratio for schizophrenia and related disorders together with bipolar disorder was 1.80 (95%CI: 0.64-5.03), and for schizophrenia and related disorders alone it was 1.19 (95%CI: 0.46-3.11), indicating higher rates of these disorders in T1DM. The pooled risk ratios were not statistically significant and did not survive sensitivity analysis. Trial sequential analysis suggested the need for more studies to confirm increased risk.

With available studies, we could not provide convincing evidence for the hypothesis that the prevalence and risk of schizophrenia and related disorders and bipolar disorder are significantly greater in individuals with T1DM.

The impact of prophylactic antibiotics on postoperative infection following laparoscopic cholecystectomy remains controversial. This meta-analysis and trial sequential analysis aims to assess the efficacy of prophylactic antibiotics in reducing the risk of postoperative infection following laparoscopic cholecystectomy.

Multiple databases including PubMed, Cochrane Library, EMBASE, and Web of Science were systematically searched to identify relevant randomized controlled trials (RCTs) published from inception to January 23, 2024. This study analyzed endpoints such as infection complications (IC) and surgical site infections (SSI). RCTs comparing prophylactic antibiotics versus placebo or no treatment in patients undergoing laparoscopic cholecystectomy were included. Data extraction and meta-analysis were performed. Additionally, trial sequential analysis was conducted to assess the robustness of evidence in meta-analysis.

Thirty-six RCTs with 9386 patients were included. The IC and SSI in prophylactic antibiotics group were significantly lower [pooled log risk-ratio (log RR): 0.37, 95 % confidence interval (CI):(-0.60, -0.14), p = 0.0017; pooled log RR: 0.30, 95 % CI (-0.51, -0.09), p = 0.01]. Trial sequential analysis revealed relative risk reductions of 33.09 % for IC and 27.96 % for SSI. Trial sequential analysis suggesting that the current evidence is robust. Studies involving low-risk patients and those with acute cholecystitis inclusion did not demonstrate a clear advantage in SSI reduction with prophylactic antibiotics.

Prophylactic antibiotics significantly reduces the risk of postoperative infection in patients undergoing laparoscopic cholecystectomy. Moreover, the lack of research on the impact of prophylactic antibiotics on postoperative infections in patients with acute cholecystitis undergoing laparoscopic cholecystectomy underscores the importance of further investigation.

To compare the refractive and visual outcomes of femtosecond laser-assisted astigmatic keratotomy (FSAK) and toric intraocular lens (IOL) implantation for correcting astigmatism in cataract patients.

Studies were retrieved from the Ovid-Medline, EMBASE, Cochrane Central Register of Controlled Trials and Scopus which compared FSAK and toric IOL for astigmatism correction in cataract patients. Outcome measures included postoperative refractive cylinder, correction index, uncorrected distance visual acuity (UDVA), the proportion of patients achieving a residual refractive cylinder of 1.00 dioptre or less, target-induced astigmatism (TIA) and surgically induced astigmatism (SIA). The trial sequential analysis (TSA) was used to collect firm evidence supporting our conclusion.

9 studies encompassing 590 participants were analysed. The meta-analysis revealed that toric IOLs could result in less postoperative refractive cylinder and provide better UDVA compared with FSAK. The TSA disclosed strong evidence of lower postoperative refractive cylinder in the toric IOL group compared with that of the FSAK group. FSAK showed a smaller correction index and lower mean TIA and SIA compared with toric IOLs.

For cataract patients, both FSAK and toric IOLs are effective methods for correcting astigmatism. However, toric IOLs offer less postoperative astigmatism and result in better postoperative UDVA compared with FSAK. In vector analysis of astigmatism, toric IOLs can also produce higher TIA and SIA. Additionally, neither method is associated with severe untreatable complications. Therefore, the conclusion is that toric IOLs are the preferred choice for astigmatism correction in cataract patients and FSAK serves as a viable alternative when toric IOLs are contraindicated.

To assess the beneficial and harmful effects of duloxetine versus 'active placebo', placebo or no intervention for adults with major depressive disorder.

Systematic review with meta-analysis and trial sequential analysis of randomised trials.

Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO and other relevant databases up until January 2023. We requested clinical study reports from 36 competent authorities.

All randomised clinical trials comparing duloxetine versus placebo, 'active placebo' or no intervention, irrespective of publication type, publication status, publication year and language for treatment of major depressive disorder in adults.

Five authors in pairs extracted data using a standardised data extraction sheet. A third review author was consulted for disagreements. Intervention effects were assessed by both random-effects and fixed-effect model meta-analyses, risk of bias assessments were performed by two independent review authors using Cochrane's risk of bias tool V.2 and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation.

We included 28 trials randomising a total of 7872 participants. All results were at high risk of bias. The trials' assessment time points were between 6 and 16 weeks after randomisation. Meta-analyses showed evidence of a beneficial effect of duloxetine on depressive symptoms (mean difference -1.81, Hamilton Depression Rating Scale (HDRS-17) points; 95% CI -2.34 to -1.28; heterogeneity I2=0.0%; 12 trials) and quality of life (mean difference -3.79 points, 95% CI -5.11 to -2.46; I2=0.0%; three trials), but the effect sizes were below our predefined minimal clinically important differences. Trial sequential analysis showed that we did not have enough information to assess the effects of duloxetine on serious adverse events (SAEs) (OR 0.67, 95% CI 0.44 to 1.02; I2=0.0%; 19 trials) or suicide or suicide attempts (OR 1.08, 95% CI 0.37 to 3.16; six trials). Duloxetine increased the risk of non-SAEs (risk ratio 1.27, 95% CI 1.22 to 1.32; I2=73.0%; 24 trials). The adverse events with the lowest number needed to harm (NNH) were nausea (NNH 6), dry mouth (NNH 13), somnolence (NNH 17), withdrawal syndrome (NNH 19), sweating (NNH 20), dizziness (NNH 21) and constipation (NNH 21).

Duloxetine appears to reduce depressive symptom scores and improve quality of life scores in the short term, but the effect sizes are minimal and of questionable patient importance. The short- and long-term effects of duloxetine on risks of SAEs and suicidality are uncertain. Duloxetine increases the risks of several short-term adverse events. Systematic assessments of benefits and harms over longer periods are required.

PROSPERO 2016 CRD42016053931.

Despite complete resection, the recurrence rate of biliary tract cancer (BTC) remains high, leading to poor prognosis. Postoperative adjuvant chemotherapy (ACT) following radical resection may substantially reduce the recurrence risk by eradicating micrometastatic lesions. However, the benefits of postoperative ACT and the optimal ACT strategy are still unclear for BTC. The objectives of this study are to evaluate the prognostic value of ACT and compare the effectiveness of different ACTs among BTC patients after curative resection.

A comprehensive literature search was conducted across PubMed, Cochrane Library, Web of Science, and EMBASE databases to identify randomized controlled trials (RCTs) comparing the benefits of ACT versus no intervention or other ACTs in BTC patients after curative resection. A random-effects network meta-analysis was performed to compare overall survival (OS) and relapse-free survival (RFS). The quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation framework.

Eight RCTs comprising 1803 patients were included in the meta-analysis. ACT was associated with significant improvements in 5-year all-cause mortality [four RCTs, hazard rate (HR) 0.93; 95% confidence interval (CI), 0.87-1.00, marginally significant; low-certainty evidence], RFS (five RCTs, HR 0.87; 95% CI, 0.78-0.98; moderate-certainty evidence), and OS (7 studies, HR 0.85; 95% CI, 0.75-0.96; low-certainty evidence) compared with observation. ACT had significantly better survival benefits on patients with negative margins (R0), lymph node-positive (N+), and tumor node metastasis classification (TNM) stage I/II ( P < 0.05). Further network meta-analysis demonstrated that fluorouracil-based ACT was significantly inferior to gemcitabine-based ACT (HR 1.20; 95% CI, 1.10-1.25) in improving RFS. However, both were superior to observation ( P < 0.05). No statistical difference in OS was observed between gemcitabine-based and fluorouracil-based chemotherapy (HR 1.00; 95% CI, 0.86-1.20). In subgroup analysis, fluorouracil-based ACT but not gemcitabine-based ACT achieved significantly better OS benefits on patients with N+ (HR 0.67; 95% CI, 0.52-0.86) and R0 (HR 0.69; 95% CI, 0.54-0.88).

Compared with observation, ACT should be routinely recommended to improve survival outcomes in BTC patients after curative resection, especially for those with R0, N+, and TNM stage I/II. Gemcitabine-based ACT performed better than other chemotherapies in improving RFS. This network meta-analysis provides precise information for determining the best adjuvant treatment for resected BTC. Further thorough and high-quality RCTs are needed.

The beneficial effects of using antidepressants in improving functional dyspepsia (FD) symptoms have been reported in previous meta-analyses; however, the results have not been conclusive. The aim was to perform an updated meta-analysis coupled with trial sequential analysis (TSA) to assess the efficacy of the use of any antidepressants in the treatment of FD in adults.

Electronic databases were searched up to March 2024 for randomized controlled trials (RCTs) recruiting adults with FD. Data of overall symptoms improved between the antidepressants and placebo groups was pooled to obtain risk ratio (RR) employing the random-effects model. The effect of random errors was evaluated with TSA. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. Analyses were performed using STATA version 16.0.

Nine RCTs with 924 patients met the eligible criteria. The RRs of FD symptoms improving with any antidepressants, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors were (n = 9, RR = 1.30 [95% CI, 1.02-1.67]), (n = 5, RR = 1.41 [95% CI, 1.07-1.85]) and (n = 2, RR = 0.97 [95% CI, 0.72-1.29]), respectively. TSA demonstrated conclusive evidence for the beneficial effect of TCAs. The number needed to treat (NNT) with any depressants and TCAs were 11 (95% CI, 7-36) and 6 (95% CI, 4-15), respectively. The certainty of the evidence for an effect of TCAs was that of moderate GRADE quality. The benefit, however, was limited to the western population (n = 3, RR = 1.43 [95% CI, 1.04-1.96]) and did not extend to the Asian population (n = 2, RR = 1.32 [95% CI, 0.75-2.32]). Conversely, antidepressant-using patients experienced adverse events more frequently. However, no statistically significant association was found between TCAs and any adverse events (n = 3; RR = 1.36 [95% CI, 0.91-2.04]).

Evidence was obtained suggesting TCAs can be an effective alternative in the treatment of FD, but more evidence from high-quality large trials is required to support their use, especially in the Asian population.

Migraine is a highly prevalent and incapacitating neurological disorder mostly characterised by recurring attacks of moderate to severe throbbing and pulsating pain on one side of the head. The role of estrogen in migraine has been well documented. Although genetic variations in the ESR1 gene have been associated with an increased risk of developing migraine, the findings are inconsistent. We performed a meta-analysis of previously published articles considering four important single nucleotide polymorphisms in the ESR1 gene (rs1801132, rs2228480, rs2234693, and rs9340799) to explore their possible association with the development of migraine and its clinical phenotypes.

We thoroughly searched literature databases, including PubMed, Science Direct, and Scopus until March 14, 2024, to identify the relevant reports. We utilized GPower software v.3 to assess the power of each report included in the meta-analysis and Comprehensive Meta-analysis v4 for all meta-analysis-related analyses. We employed funnel plots and Egger's regression test to identify publication biases within each genetic comparison model. We used Cochrane Q statistics, probability value, and I2 to assess heterogeneity.

After applying predefined criteria, a meta-analysis was conducted with 11 relevant studies comprising 3835 cases of migraine and 3655 healthy individuals. The analysis indicated a strong correlation between ESR1 polymorphisms (rs2228480 and rs9340799) and the likelihood of developing migraine. Furthermore, the subgroup analysis showed that rs2228480 is associated with susceptibility to migraine in both Caucasians and Asians. Additionally, rs2234693 variants were found to be linked with the development of migraine with aura. However, the trial sequential analysis suggested that more case-control studies are necessary to establish the definitive role of ESR1 variants in migraine.

ESR1 variants (rs2228480, rs2234693, and rs9340799) are associated with an increased risk of migraine and related phenotypes. However, further studies are needed to establish a definitive conclusion.