AIM:The aim of this study is to evaluate the efficacy and safety of blood-activating and stasis-removing Chinese patent medicines (BASR-CPMs) during the perioperative period of percutaneous coronary intervention (PCI) for myocardial infarction (MI). METHODS:We searched eight databases (PubMed, Embase, the Cochrane Library, Web of Science, CNKI, WanFang Data, SinoMed, and VIP) from database inception to February 15, 2025, for randomized controlled trials (RCTs) comparing standard care plus BASR-CPMs versus standard care alone (or with other BASR-CPMs) in MI patients undergoing PCI. A Bayesian network meta-analysis was conducted to estimate relative effects. Primary outcomes included major adverse cardiovascular events (MACE) and major adverse cardiac and cerebrovascular events (MACCE), while key secondary outcomes included thrombolysis in MI (TIMI) grade 3 flow, angina, and bleeding events. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. The certainty of evidence was evaluated using the GRADE framework. A protocol of the systematic review and network meta-analysis was registered with PROSPERO (CRD420251048208). RESULTS:We included 160 RCTs (21,147 participants) evaluating 25 BASR-CPMs. Regarding hard clinical endpoints, no BASR-CPMs differed significantly from standard care for MACE or MACCE at any time point. For example, Tongxinluo capsule showed no significant reduction in MACE at 1 month (relative risk [RR] 0.62, 95% credible interval [CrI] 0.11 to 1.70; low certainty). Tongxinluo capsule may improve TIMI grade 3 flow immediately after PCI (RR = 1.12, 95% CrI: 1.04-1.26; low certainty) and at 3 months (RR = 1.47, 95% CrI: 1.10-1.98; moderate certainty). Danhong injection (RR = 1.15, 95% CrI: 1.02-1.31) and Shexiang Baoxin pill (RR = 1.15, 95% CrI: 1.02-1.30) may also improve TIMI grade 3 flow immediately after PCI (moderate certainty). For reducing angina incidence at 1 and 6 months, Tongxinluo, Danhong, Salvianolate injection, Shexiang Baoxin, Guanxin Shutong, and Shexiang Tongxin dripping pill showed potential benefits (low to high certainty). Most interventions did not increase bleeding risk, and Tongxinluo possibly reduced adverse effects (low certainty). CONCLUSIONS:Exploratory findings suggest that BASR-CPMs, notably Tongxinluo, Danhong, and Shexiang Baoxin, improve immediate reperfusion and reduce angina recurrence post-PCI in MI patients. These intermediate benefits do not translate into reductions in hard clinical outcomes. Further rigorous RCTs are needed to confirm their long-term impact on MACE and MACCE.

Background Lung cancer remains the world’s heaviest societal health burden.Objective To provide 2022 global lung cancer estimates and predict trends through Mid-century.Methods Based on GLOBOCAN 2022, the burden and epidemic trend of lung cancer in 2022 and number of new cases and deaths by 2050 were analyzed and predicted.Results In 2022, a total of 2,480,675 new cases of lung cancer and 1,817,469 related deaths were reported worldwide. Incidence rate of lung cancer was highest in East Asia (ASR = 39.7) and North America (ASR = 31.9). For mortality, East Asia had the highest lung cancer mortality (ASR = 26.7), Western Europe the second highest mortality (ASR = 22.1), and West Africa the lowest mortality rate (ASR = 2.0). Among entire sex group, the incidence and mortality of lung cancer were mainly concentrated in male. By 2050, it was expected that there will be an additional 2.14 million cases (42.2%) and 1.73 million deaths (50.3%) from lung cancer.Conclusions This study revealed the differences in incidence rate and mortality rate of lung cancer from the world in 2022. It is expected that the incidence and mortality of lung cancer will rise sharply in the next few decades, especially in socially and economically developed regions and countries.

To systematically evaluate the effect of preoperative mechanical bowel preparation combined with oral antibiotics on surgical site infection after elective rectal resection. PubMed, Web of Science, Embase, Cochrane library, CNKI database, Wanfang database, Chinese Science and Technology Journal full text database, Chinese Biomedical Literature Database, In addition, the relevant studies on the effects of mechanical bowel preparation before rectal resection combined with oral antibiotics and surgical site infection were systematically searched in Chinese ClinicalTrial Registry and ClinicalTrials.gov until 2 October 2025. References were screened according to inclusion and exclusion criteria, literature quality assessment and data extraction were performed, and data analysis was performed using RevMan 5.3 software. 8 studies including 7516 patients with rectal tumours were included. The results of the meta-analysis showed that preoperative mechanical bowel preparation combined with oral antibiotics was associated with a lower risk of surgical site infection (RR = 0.46, 95

Metabolism-associated steatotic liver disease (MASLD) is one of the most prevalent chronic liver diseases worldwide. In recent years, although a network meta-analysis evaluated the efficacy of different drugs for patients with MASLD, it did not provide the specific dosage of the drugs and could not be accurately applied to the specific population for MASLD and fibrosis stages F1–F3, which greatly affected the extensibility and accuracy of the evidence. Therefore, this study aimed to evaluate the efficacy of various pharmacotherapies with different dosages in improving liver fibrosis among MASLD patients with fibrosis stages F1–F3 through a network meta-analysis. Randomized controlled trials involving adults with MASLD and fibrosis stages of F1–F3 who received pharmacological interventions for improving liver fibrosis from three databases were identified from inception to July 21, 2025. Thirteen RCTs involving 3,871 patients with 12 pharmacological interventions were involved. Compared with placebo in this network meta-analysis, 6 active pharmacological interventions, including resmetirom 80 mg/day (RR = 2.56, 95

BackgroundMyocardial infarction (MI) poses a formidable health challenge, frequently necessitating management through percutaneous coronary intervention (PCI). However, PCI comes with potential complications that can impact patient outcomes. Traditional Chinese medicine (TCM), particularly the utilization of Chinese patent medicines with blood-activating and stasis-resolving properties, offers another approach to enhance PCI efficacy and improve patient quality of life. The aim of this study is to assess the comparative efficacy and safety of blood activating and stasis removing Chinese patent medicines for the perioperative period of PCI for MI.MethodsThis systematic review and network meta-analysis will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy will be implemented across seven electronic databases to identify relevant studies. Eligible studies will be limited to randomized controlled trials that compare any Chinese patent medicine (added to standard care) with standard care or another treatment in patients in the perioperative period of PCI after MI. Two independent reviewers will screen all retrieved citations, extract pertinent data, and assess the risk of bias. We will conduct Bayesian random-effects network meta-analysis and network meta-regression. To elucidate whether the intervention has an important impact on certain outcomes within the perioperative period of PCI for MI, we will conduct a patient values and preferences survey to determine the minimum important difference for outcomes. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.DiscussionThis study will provide new insights into the efficacy and safety of blood activating and stasis removing Chinese patent medicines for the perioperative period of PCI for MI patients, providing help for future clinical practice and research.Ethics and disseminationEthical approval is not required for this review. The findings will be disseminated through publication in a peer-reviewed academic journal, presentations at scientific conferences, and outreach via various media platforms.

Pulpotomy is a commonly used approach for treating deep caries in primary teeth. In recent years, diode lasers have been explored the use in pulpotomy. This study systematically reviewed the clinical and radiographic efficacy of diode lasers in pulpotomy and evaluated their feasibility and safety as an alternative treatment modality. This systematic review searched PubMed, Embase and the Cochrane Library for all published articles in the English language from inception to August 31, 2025. The medical subject headings (MeSH) terms and free-text keywords were used. The Cochrane collaboration risk assessment tool was used to evaluate the quality of the literature. Meta-analysis was performed using RevMan 5.4. Heterogeneity was evaluated using Cochran’s Q test and the I2 statistic. The results of this study showed that comparing with other treatments, no significant differences in clinical or radiographic success rates at every follow-up period (P > 0.05). However, diode lasers significantly decreased the occurrence of pathologic widening of the periodontal space (P < 0.05). Laser wavelength did not significantly influence the outcome (P > 0.05). When using zinc oxide eugenol (ZOE) as the pulp capping material, diode lasers lowered the incidence of pathological widening of the periodontal ligament space (P < 0.05). Sensitivity analyses confirmed that most results were consistent, although some subgroup outcomes were affected when individual studies were excluded. Funnel plot examination indicated no evidence of publication bias. Compared with other methods, diode laser treatment demonstrated similar clinical and radiographic success rates and showed potential benefits in reducing the incidence of pathologic widening of periodontal space. Therefore, diode laser-assisted pulpotomy may be considered a viable alternative therapy. The study was submitted to the Open Science Framework platform [https://osf.io/rweuq/overview?view_only=fa297ad91199454581a03dedc1b3d4e0].

Background Intracerebral haemorrhage (ICH) is a critical condition that leads to significant mortality or profound disability. Surgery serves as an important intervention that can save lives; however, the surgical techniques employed globally exhibit considerable variability, and their efficacy remains ambiguous.Methods PubMed, Embase, Web of Science and CENTRAL were searched for randomised controlled trials (RCTs). Two independent reviewers extracted data, assessed bias (Cochrane Risk of Bias Tool, V.2) and evidence certainty (Confidence in Network Meta-Analysis). Frequentist network meta-analysis calculated relative risks (RRs) and 95% CIs.Results A total of 26 RCTs with 4892 patients with ICH were included. The very-low-certainty evidence network meta-analysis demonstrated that, compared with standard medical care, both endoscopic surgery (mortality: RR 0.66; 95% CI 0.50 to 0.87) and minimally invasive puncture surgery (mortality: RR 0.77; 95% CI 0.64 to 0.93) were associated with decreased mortality. Moreover, low-certainty evidence showed that endoscopic surgery (functional independence: RR 1.62; 95% CI 1.28 to 2.05) and minimally invasive puncture surgery (functional independence: RR 1.53; 95% CI 1.34 to 1.76) were associated with a higher likelihood of functional independence. In contrast, conventional craniotomy (mortality: RR 0.86; 95% CI 0.72 to 1.02; functional independence: RR 1.07; 95% CI 0.90 to 1.28) showed no statistically significant differences.Conclusions This systematic review and network meta-analysis found that endoscopic surgery and minimally invasive puncture surgery were associated with lower mortality and better functional outcomes compared with other interventions. However, the certainty of evidence was limited due to heterogeneity in patient populations and treatment protocols. More definitive conclusions will require future large-scale, rigorously designed RCTs that standardise protocols and minimise confounding factors.

Abstract Background and aims Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke (IS) and transient ischemic attack (TIA). Plaque characteristics can be assessed using vessel wall magnetic resonance imaging (vwMRI). We aimed to synthesize evidence on the associations between vwMRI plaque features and recurrent IS/TIA in medically treated symptomatic ICAS (sICAS). Methods We systematically searched the literature (past 20 years) for relevant studies. The primary outcome was recurrent IS/TIA in the same territory; the secondary outcome was any recurrent IS/TIA during follow-up. Effect estimates were pooled as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs) for each plaque feature using random-effects models. For the primary outcome, leave-one-out sensitivity analyses were conducted. Results Overall, 25 studies (n=3,760) were eligible for systematic review, among which 23 studies (n=3,333) were included in meta-analysis for 20 plaque metrics. Patients with a primary outcome had significantly larger plaque burden (n=1,101, MD=0.04, 95% CI 0.02-0.05) and higher enhancement ratio (n=478, MD=0.31, 0.10-0.51), and were more likely to have positive remodeling (n=775, RR=1.58, 1.09-2.29), irregular plaque surface (n=469, RR=1.72, 1.03-2.89), and significant plaque enhancement (n=738, RR=2.47, 1.71-3.56). Findings remained consistent in sensitivity analyses. Moreover, positive remodeling (n=460, RR=1.67, 1.15-2.43), any plaque enhancement (n=922, RR=2.53, 1.67-3.85), significant plaque enhancement (n=363, RR=1.78, 1.19-2.68), and intraplaque hemorrhage (n=784, RR=1.62, 1.01-2.61) were significantly associated with the secondary outcome. Conclusions Plaque features assessed on vwMRI were associated with same-territory and any IS/TIA recurrence in medically treated sICAS patients, which can facilitate stroke risk stratification. Conflict of interest Yue Gu, Chao Zhang, Xuan Tian, Yue Wang, Thomas W Leung, Binbin Sui, Xinyi Leng: nothing to disclose.

INTRODUCTION:Gestational trophoblastic neoplasia (GTN) is highly chemosensitive, but resistance to initial chemotherapy remains clinically important despite International Federation of Gynecology and Obstetrics (FIGO) score-guided management. Evidence on pretreatment predictors of chemoresistance and comparative chemoresistance across chemotherapy regimens remains limited. This study aimed to estimate the burden of chemoresistance, identify pretreatment risk factors, and compare chemotherapy regimens using pairwise and network meta-analysis to inform risk stratification and future treatment optimization. MATERIAL AND METHODS:Eight databases (PubMed, Embase, Cochrane Library, Web of Science, CBM, CNKI, VIP, and Wanfang) were searched from inception to August 26, 2025. Two reviewers independently screened records, extracted data, and assessed risk of bias using the RTI Item Bank. Pairwise meta-analyses were used to pool the chemoresistance rate and evaluate associations between pretreatment factors and chemoresistance. A frequentist random-effects network meta-analysis was performed to compare chemoresistance risks across chemotherapy regimens, with ranking probabilities summarized using the surface under the cumulative ranking curve (SUCRA). RESULTS:Fifty-three studies involving 7585 patients and 1997 resistant cases yielded a pooled chemoresistance rate of 23.8% (95% CI: 20.7%-27.1%; p < 0.001). Higher chemoresistance was associated with choriocarcinoma, antecedent full-term pregnancy, a high FIGO score, higher pretreatment β-hCG, especially > 105 IU/L, longer intervals from antecedent pregnancy (7-12 and > 12 months), greater tumor burden (tumor diameter ≥5 cm, presence of metastasis, and ≥ 5 metastatic lesions), FIGO stage II or IV disease, and first-line single-agent chemotherapy. In exploratory ranking analyses, methotrexate (MTX) and fluorouracil (FU) tended to rank higher for predicted chemoresistance, whereas etoposide (ETP) and FU + actinomycin D + etoposide + vincristine (FAEV) tended to rank lower. CONCLUSIONS:Approximately one quarter of patients with GTN develop chemoresistance. Pretreatment factors, including clinicopathologic type when available, tumor burden, FIGO score and stage, antecedent pregnancy characteristics, and pretreatment β-hCG level, may help identify patients at higher risk of chemoresistance. Exploratory regimen-ranking analyses suggested lower predicted chemoresistance for etoposide-containing regimens, particularly FAEV; however, these findings require prospective validation before they can inform treatment selection.

Aims:Osteoporosis poses a substantial public health burden. The conicity index (C-index), which integrates waist circumference, weight, and height, is a validated measure of abdominal obesity. However, its association with osteoporosis and femoral bone mineral density (BMD) remains unclear. Methods:This study analyzed data from 16,218 USA adults (aged ≥ 20 years) in the 2005 to 2020 National Health and Nutrition Examination Survey (NHANES). Associations between C-index and osteoporosis were assessed by weighted multivariable logistic regression, while associations between C-index and femoral BMD (total femur, neck, trochanter, intertrochanter) were evaluated by weighted multivariable linear regression. Potential non-linearity was explored via generalized additive models with smooth curve fitting. Threshold effect and dose-response analyses were performed, and robustness was tested by subgroup analyses. Results:After full adjustment for confounders, participants in the highest C-index quartile (Q4) had significantly higher odds of osteoporosis than those in the lowest quartile (Q1) (OR 1.67 (95% CI 1.23 to 2.27); p = 0.001). Each one-unit increase in C-index was associated with statistically significant decreases in BMD, as follows: total femur (-0.17 g/cm2), femoral neck (-0.18 g/cm2), trochanter (-0.17 g/cm2), and intertrochanter (-0.18 g/cm2). These associations persisted in subgroup analyses. A non-linear relationship was identified between C-index and femoral BMD. Conclusion:Elevated C-index independently predicts osteoporosis risk and femoral BMD reduction in USA adults, with critical thresholds indicating accelerated bone loss. It thus serves as a clinically actionable metric for osteoporosis risk stratification in abdominal obesity management.

Global burden of opioid use disorders (OUD) has risen substantially, posing major socioeconomic challenges. Cross-spatiotemporal disease burden comparison using data sourced from Global Burden of Disease 2021. We comprehensively assessed OUD’s epidemiological burden using multiple metrics and the socio-demographic index (SDI), estimated annual percentage changes (EAPCs), and integrated estimates through Bayesian meta-regression. Disability-adjusted life years (DALYs) of OUD demonstrated a significant upward trend. Specifically, DALYs of OUD increased from 5,415,249 (95%UI: 4,242,001 to 6,437,812) in 1990 to 11,218,519 (95%UI: 9,188,658 to 13,159,551) in 2021. Over these three decades, burden of OUD shifted considerably across regions with different SDI, with the highest burden transitioning from high-middle SDI regions to high SDI regions, where age-standardized DALY rate in 2021 was 587.41 (95%UI: 484.84 to 680.69). While males had a higher overall burden, females bore a disproportionate burden at older ages, and their deaths rose sharply over 30 years, narrowing the gap with males. Global burden of OUD is rising, especially in high-income countries. Despite higher prevalence in males, female mortality has increased over the past three decades. This study provides crucial evidences for policy and resource allocation in high-burden areas and calls for multinational collaboration.

Diabetes and metabolic syndrome are major public health challenges closely linked to oxidative stress, inflammation, and impaired insulin signaling. Selenium, an essential trace element with antioxidant and immunomodulatory roles, has been proposed as an adjunctive strategy for metabolic regulation; however, evidence from randomized trials remains inconsistent. We evaluated the effects of selenium supplementation on glycemic indices, oxidative-stress-related biomarkers, lipid metabolism, and related metabolic indicators in adults, and explored potential effect modifiers. We searched PubMed, Embase, Cochrane CENTRAL, Web of Science, CINAHL, CNKI, WanFang, VIP, and SinoMed through 12 August 2025 for randomized controlled trials of oral selenium supplementation in adults, including pregnant women with gestational diabetes mellitus (GDM). Outcomes included fasting plasma glucose, glycated hemoglobin, fasting insulin, indices of insulin resistance and β-cell function, oxidative-stress-related and inflammatory biomarkers, lipid parameters, and anthropometric and hemodynamic indicators. Random-effects meta-analyses estimated weighted mean differences with 95

BACKGROUND:Distal medium vessel occlusions (MeVOs) account for an estimated 25% to 40% of all acute ischemic strokes. Emerging evidence from non-randomized trials suggest that endovascular thrombectomy (EVT) can achieve high rates of successful reperfusion in MeVO strokes, with a safety profile comparable to EVT for proximal arterial occlusions. These findings underscore the need for a prospective randomized clinical trial to evaluate the safety and efficacy of EVT for MeVO stroke. OBJECTIVE:This trial aims to evaluate the safety and efficacy of EVT for MeVO stroke. METHODS AND DESIGN:Endovascular treatment in acute intracranial distal medium vessel occlusion stroke (ORIENTAL-MeVO) is an investigator-initiated, multicenter, prospective, randomized clinical trial with open-label treatment and blinded endpoint assessment (PROBE). Up to 564 eligible patients will be consecutively randomized in a 1:1 ratio to receive either EVT or standard of care over a period of 2 years in over 50 comprehensive stroke centers in China. OUTCOMES:The primary outcome is a shift in the distribution of the modified Rankin Scale (mRS) at day 90s with levels 5-6 combined (mRS = 0, 1, 2, 3, 4, 5-6). Primary safety endpoints include symptomatic intracerebral hemorrhage at 24 h and mortality at 90 days. TRIAL REGISTRATION:ClinicalTrials.gov NCT06146790.

Post-traumatic stress disorder (PTSD) is strongly associated with sleep disorders, and current clinical guidelines for PTSD differ in recommending treatment for patients with PTSD associated with sleep disorders. This meta-analysis evaluates the acceptability and efficacy of psychotherapy, pharmacotherapy, and other complementary/alternative therapies, to help clinicians make decisions about treatment regimens for individuals with PTSD and sleep disorders. We systematically searched PubMed, EMBASE, the Cochrane Library, and American Psychological Association PsyNet for randomized controlled trials (RCTs) related to placebo-controlled and active intervention trials for PTSD with sleep disorders up to February 2, 2023. Active intervention significantly improved PTSD (standardized mean difference (SMD) = 0.86, 95

BACKGROUND:Intracerebral hemorrhage represents a critical subtype of stroke, imposing substantial social and economic challenges. Considering the considerable impact of intracerebral hemorrhage in Asia and the absence of studies detailing its epidemiological features, the aim of this study was to elucidate the temporal trends and distribution characteristics of intracerebral hemorrhage in Asia from 1990 to 2021, as well as to forecast the future burden. METHODS:The data derived from Global Disease Burden Study 2021 were used to investigate the age-standardized rates and absolute numbers of incident intracerebral hemorrhage cases and related deaths in Asia across genders, age groups, and geographical locations. An estimated annual percentage change was estimated to represent temporal trends, and an autoregressive integrated moving average model was used to forecast the future burden. RESULTS:In Asia, the age-standardized incidence and mortality rates of intracerebral hemorrhage per 100,000 population have declined from 1990 to 2021, despite a continuous increase in the absolute numbers, which exhibit significant heterogeneity across different geographical locations. In terms of gender, males experience a greater burden of intracerebral hemorrhage compared to females, and the impact of risk factors on disability-adjusted life years of intracerebral hemorrhage varies. In comparison to the figures observed in 2021, our forecasts indicate a rise in the burden of intracerebral hemorrhage in Asia. CONCLUSIONS:The study offers an extensive depiction of the epidemiological features of intracerebral hemorrhage in Asia spanning from 1990 to 2021 while also outlining the diverse trajectories of the impending burden of this condition in the region. Comprehending the expected increase in disease burden can aid in formulating tailored strategies to tackle upcoming challenges.

Evidence is a core element of evidence-based medicine, with diverse classifications and extensive sources. Most of it is based on journals and is commonly found in databases or websites such as PubMed, Web of Science, and CNKI. The number of literatures is countless, which also puts enormous pressure on researchers to consult and read literature. The field of urology is no exception. This article started with analyzing the characteristics of common clinical questions in the field, introduced the four criteria for their screening and two types of structured templates, clarified the definition, categories, identification, and three requirements for the application of the four evidence classification methods, and explained the selection of retrieval resources, construction of retrieval strategies, specific operational steps, and precautions for the retrieval process to develop and use evidence. In addition, combined with artificial intelligence technology, the future development trend of evidence classification and retrieval in the field of evidence-based urology has been clarified, which provided reference for further promoting the development of evidence-based urology.

OBJECTIVE:This study aimed to identify the optimal strategy for patients with autoimmune diseases by comparing the immunoreaction and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines between healthy individuals and patients. METHODS:The PubMed, Embase, and Cochrane Library were searched for eligible studies on effectiveness and immunoreaction to SARS-CoV-2 vaccines in patients with autoimmune diseases published until October 07, 2022. The quality of each included study was evaluated by independent reviewers using National Institutes of Health study quality assessment tool, and the STATA 15.0 software was used for all statistical analyses. RESULTS:A total of 84 publications were included and analyzed in this meta-analysis, favoring healthy controls regarding serological response (risk ratio, RR=0.88, 95% CI (confidence interval): 0.86-0.91), antibody response (RR=0.90, 95%CI: 0.87-0.94), and incidence of seropositive immunoglobulin G (IgG) (RR=0.74, 95%CI: 0.69-0.80) than patients post-vaccination. Patients with autoimmune diseases developed lower IgG (standard mean difference, SMD=-0.64 95%CI: -0.84 to -0.43) and antibody titer level (SMD=-1.39, 95%CI: -2.30 to -0.49) than healthy individuals in AU/ml. Stratified analyses were conducted further according to various potential factors in full-text studies. CONCLUSION:Patients who are immunocompromised and received more vaccines demonstrated poorer humoral responses and seropositive incidence after SARS-CoV-2 vaccination than healthy individuals. Despite the lack of observable favor for patients with autoimmune diseases, the trend of effectiveness of SARS-CoV-2 vaccines is close to that for healthy populations. Patients who are immunocompromised should be provided a better SARS-CoV-2 vaccination schedule, considering various vaccine subtypes, dose(s), variants of concern, and immunoassays.

Objective To investigate the impact of retracted trials on the production and use of healthcare evidence in the evidence ecosystem. Design Retrospective cohort study based on forward citation searching. Data sources Retraction Watch up to 5 November 2024. Study selection Randomised controlled trials in humans that were retracted for any reason. Methods Forward citation searching via Google Scholar and Scopus was used to identify evidence synthesis research (21 November 2024) that quantitatively incorporated retracted trials. Data were independently extracted by two groups of researchers. The results of meta-analyses were updated after exclusion of the retracted trials. The proportions of meta-analyses that changed direction of the pooled effect and/or the significance of the P value were estimated. A generalised linear mixed model was used to investigate the association between the number of included studies and the impact, measured by odds ratio and 95% confidence interval (CI). The impact of distorted evidence on clinical practice guidelines was also investigated on the basis of citation searching. Results The searches identified 1330 retracted trials and 847 systematic reviews that quantitatively synthesised retracted trials, with a total of 3902 meta-analyses that could be replicated. After the potential clustering effects were accounted for, the exclusion of the retracted trials led to a change in the direction of the pooled effect in 8.4% (95% CI 6.8% to 10.1%), in its statistical significance in 16.0% (14.2% to 17.9%), and in both direction and significance in 3.9% (2.5% to 5.2%) and a >50% change in the magnitude of the effect in 15.7% (13.5% to 17.9%). An obvious non-linear association existed between the number of included studies and the impact on the results, with a lower number of studies having higher impact (eg, for 10 studies versus ≥20 studies, change of direction: odds ratio 2.63, 95% CI 1.29 to 5.38; P<0.001). Evidence from 68 systematic reviews with conclusions distorted by retracted trials was used in 157 guideline documents. Conclusion Retracted trials have a substantial impact on the evidence ecosystem, including evidence synthesis, clinical practice guidelines, and evidence based clinical practice. Evidence generators, synthesisers, and users must pay attention to this problem, and feasible approaches that assist with easier identification and correction of such potential contamination are needed. Study registration Open Science Framework ( https://osf.io/7eazq/ ).

The global ageing trend is accelerating, leading to an increase in chronic diseases and posing a significant health challenge. Stroke, characterised by high rates of disability and mortality, is emerging as one of the most critical public health issues. The aim of this study was to examine current trends in global ageing and, under this condition, to assess the burden of stroke, with a focus on the elderly population at high risk of stroke. The data utilised in this study was obtained from the Global Burden of Diseases Study 2021, which estimated the burden of stroke and its subtypes, including ischaemic stroke, intracerebral hemorrhage, and subarachnoid haemorrhage focusing on incidence, mortality, and disability-adjusted life year (DALY) rates. To investigate the correlation between ageing and stroke burden as well as its temporal trends, Pearson correlation analysis, decomposition analysis, and estimated annual percentage change were conducted. Globally, the proportion of countries entering ageing society has almost doubled, rising from 30.4% in 1990 to 52.5% in 2021. The Pearson correlation coefficient showed a significant positive association between stroke burden and the degree of ageing, particularly for incidence rate (R=0.64, P<2.2e-16) and mortality rate (R=0.44, P=5.3e-16). In addition, the global increase in stroke DALYs from 1990 to 2021 was largely attributable to population ageing, which accounted for 99.9% of this increase. In more than half of the countries, the burden of stroke was mainly concentrated in the elderly population aged 65 years and above, especially for ischaemic stroke, while the younger population predominantly borne the burden of haemorrhagic stroke. Despite the observed reductions in the incidence, mortality and DALY rates of stroke and its subtypes, the overall absolute numbers were still on an upward trajectory. Significantly, the majority of the burden of stroke was borne by the elderly. Therefore, the promotion of healthy ageing worldwide is critical and requires the rapid and effective development and implementation of appropriate public health policies and preventive management strategies to reduce the expected increase in the burden of stroke in the near future, particularly in the face of the challenges of global ageing wave.

Objective:To evaluated the effectiveness and safety of single anti-seizure medication (ASM) when used as adjunctive therapy for drug-resistant focal epilepsy. Methods:We conducted a comprehensive search of PubMed, EMbase, and the Cochrane Library from their inception until 12 February, 2025, to identify randomized controlled trials (RCTs) meeting our criteria. The trials were analyzed for their use of ASMs in treating drug-resistant focal epilepsy. Inclusion criteria comprised: 1) Participants aged 12 years or older with drug-resistant focal epilepsy; 2) Incorporation of an additional single ASM as an adjunct to the existing antiepileptic treatment regimen; 3) Comparison with placebo or continuation of the original antiepileptic regimen without a new ASM; 4) Primary outcome as a 50% response rate, with safety as a secondary outcome, encompassing dizziness, somnolence, headache, ataxia, diplopia, fatigue, and nausea; and 5) Study design limited to RCTs. The surface under the cumulative ranking curve (SUCRA) was employed to rank the effectiveness and safety of the ASMs. Results:A total of 53 RCTs involving 17 ASMs as adjunctive therapy and placebo were analyzed. Compared to placebo, the following ASMs demonstrated statistically significant effectiveness in achieving a 50% response rate: brivaracetam (RR = 2.07, 95% CI: 1.53-2.81), cenobamate (RR = 2.12, 95% CI: 1.56-2.88), eslicarbazepine acetate (RR = 1.95, 95% CI: 1.41-2.70), gabapentin (RR = 2.30, 95% CI: 1.76-3.02), lacosamide (RR = 2.22, 95% CI: 1.47-3.35), lamotrigine (RR = 1.55, 95% CI: 1.00-2.40), levetiracetam (RR = 2.43, 95% CI: 1.88-3.15), oxcarbazepine (RR = 3.03, 95% CI: 2.08-4.40), perampanel (RR = 1.72, 95% CI: 1.21-2.44), pregabalin (RR = 2.06, 95% CI: 1.70-2.50), rufinamide (RR = 2.28, 95% CI: 1.20-4.31), tiagabine (RR = 4.07, 95% CI: 2.03-8.18), topiramate (RR = 3.10, 95% CI: 2.44-3.95), vigabatrin (RR = 2.34, 95% CI: 1.58-3.46), and zonisamide (RR = 2.40, 95% CI: 1.76-3.27). Based on SUCRA rankings, tiagabine (92.7%) exhibited the most favorable therapeutic outcome, followed by topiramate (87.3%), oxcarbazepine (83%), and levetiracetam (62.8%). The ASMs with the least favorable therapeutic effects were placebo (1.1%), lamotrigine (17.8%), and perampanel (24.7%). Conclusion:The network meta-analysis revealed topiramate, tiagabine, oxcarbazepine, and levetiracetam as the four most effective adjuvant ASM treatments for drug-resistant focal epilepsy. However, it is noteworthy that topiramate and oxcarbazepine were associated with a higher incidence of somnolence. Additionally, comprehensive safety data for tiagabine and levetiracetam are lacking, necessitating further research. Larger studies are required to solidify these findings and better understand the safety profiles of all involved ASMs.