BMC Medicine最新文献

{"title":"Healthcare access among sub-Saharan migrants and refugees in Tunisia: an interpretative qualitative study.","authors":"Taha Maatoug, Anissa Ouahchi, Farah Seedat, Anna Deal, Abdedayem Khelifi, Mohamed Douagi, Wejdene Mansour, Ali Mtiraoui, Bouchra Assarag, Ana Requena-Méndez, Dominik Zenner, Stella Evangelidou","doi":"10.1186/s12916-025-04383-6","DOIUrl":"10.1186/s12916-025-04383-6","url":null,"abstract":"<p><strong>Background: </strong>Tunisia, situated at the crossroads of North Africa and Europe, has increasingly become an important origin, destination, and transit point for sub-Saharan migrants and refugees in recent decades. Despite growing migration flows, there remains a paucity of research on how these populations navigate healthcare access in Tunisia. This study addresses this gap by exploring migrants' experiences with and perceptions of Tunisia's healthcare system, with a focus on barriers to and facilitators of healthcare.</p><p><strong>Methods: </strong>A qualitative study was conducted in four urban areas (Tunis, Medenine, Sousse, and Sfax) with concentrated migrant populations between May and December 2023. A purposive sample of migrants, migrant community leaders, and nongovernmental organization (NGO) staff were engaged through semi-structured interviews and focus-group discussions. Data were analysed via thematic analysis, combining inductive and deductive coding via NVivo 14 software, guided by an adaptation of Levesque's conceptual framework.</p><p><strong>Results: </strong>In total, 120 migrants and 43 NGO staff members participated in the study. The participants identified structural barriers such as legal status limitations, language barriers, and financial constraints, as well as social and cultural issues such as stigma and distrust of health system. While informal networks provide critical health information, they often lead to fragmented care. The private sector was perceived as better quality but unaffordable for the majority of migrants. Key facilitators included NGO support for referrals and coordination, particularly for undocumented migrants. Access was further hindered by communication gaps and limited awareness of the healthcare process.</p><p><strong>Conclusions: </strong>Our study underscores the complex interplay of structural and individual barriers to accessing healthcare for migrants in Tunisia. Addressing these challenges requires culturally sensitive policies, multilingual resources, simplified administrative processes, and expanded health insurance coverage. Strengthening collaboration between NGOs, healthcare providers, and policymakers is essential to ensure equitable healthcare access for migrants.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"547"},"PeriodicalIF":8.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated VAMP8 expression promotes cervical cancer progression by enhancing autophagy via HIF-1 pathway.","authors":"Yue Wang, Dan Wu, Jinxia Gai, Yiying Cai, Keqin Hua, Zhiling Zhu, Weijuan Xin","doi":"10.1186/s12916-025-04378-3","DOIUrl":"10.1186/s12916-025-04378-3","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer, prevalent in low- and middle-income countries, is primarily caused by high-risk HPV16. Vesicle-Associated Membrane Protein 8 (VAMP8), involved in vesicle trafficking and autophagy, may influence HPV16-related cervical cancer progression.</p><p><strong>Methods: </strong>VAMP8 expression was evaluated in cervical tissue specimens from patients with HPV16-positive lesions (including low- and high-grade squamous intraepithelial lesions and cancer) and HPV-negative normal controls using proteomics, qPCR, and immunohistochemistry. A Cox proportional hazards model for prognosis was developed using immunohistochemical data from a cohort of cervical cancer patients. The clinical significance of VAMP8 was further assessed using RNA-seq and clinical data from The Cancer Genome Atlas-Cervical Cancer (TCGA-CESC) cohort. The effects of VAMP8 on autophagy and tumor progression were examined in HPV16 E6/E7-immortalized cervical epithelial cells (Ect1/E6E7) and cervical cancer cell lines (SiHa, HeLa, C-33A) in vitro, and in a SiHa xenograft model in vivo. Transcriptomic analysis of Ect1/E6E7 and SiHa cells identified VAMP8-regulated pathways. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays in SiHa cells were used to confirm the regulation of the HIF-1 pathway.</p><p><strong>Results: </strong>VAMP8 was upregulated in HPV16-positive samples, particularly in low-grade squamous intraepithelial lesions (LSIL). Elevated VAMP8 correlated with poor survival outcomes and advanced tumor stages. VAMP8 enhanced autophagy and reduced proliferation and invasiveness in HPV16-positive cervical cells but increased in established cancer cell lines. In vivo, VAMP8 overexpression promoted tumor growth and autophagy. The HIF-1 pathway emerged as a key regulatory axis of VAMP8, enhancing hypoxic responses and angiogenesis.</p><p><strong>Conclusion: </strong>Elevated VAMP8 in HPV16-associated cervical cancer promotes tumor progression by enhancing autophagy via the HIF-1 pathway, suggesting its potential as a diagnostic and prognostic biomarker.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"544"},"PeriodicalIF":8.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-assisted endoscopic diagnosis system for diagnosing Helicobacter pylori infection: a multicenter study.","authors":"Yue Hu, Jianwei Xu, Liang Huang, Zhilin Zheng, Jin Zhao, Tanzhou Chen, Jiang Liu, Fangfang Zhang, Xiaoyun Ding, Jie Pan, Xiaoteng Wang, Shan Liu, Ling Zhang, Bin Lv","doi":"10.1186/s12916-025-04379-2","DOIUrl":"10.1186/s12916-025-04379-2","url":null,"abstract":"<p><strong>Background: </strong>Deep learning algorithm-based artificial intelligence (AI) has significantly advanced the domain of endoscopic diagnosis; however, its utilization for detecting Helicobacter pylori (H. pylori) infections remains constrained. We aimed to develop and validate the AI diagnostic system (HOPE AI) for diagnosing H. pylori infection by analyzing extensive imaging data obtained from clinical endoscopies.</p><p><strong>Methods: </strong>This multicenter diagnostic study was carried out across seven hospitals in China. Eligible patients were individuals aged 18 years or older who underwent upper gastrointestinal gastroendoscopy. The endoscopic images were randomly allocated (7:3) to the training and internal validation datasets for the development of HOPE AI, utilizing a multi-instance learning (MIL) framework and long short-term memory (LSTM) architectures, and the prospective external validation dataset for assessing its diagnostic efficacy. The performance of HOPE AI was also benchmarked against endoscopists. The diagnostic accuracy, sensitivity, specificity, and area under the curve of HOPE AI were assessed to detect H. pylori infection.</p><p><strong>Results: </strong>A total of 308,887 endoscopic images and 197 videos from 6207 patients were utilized to develop and evaluate HOPE AI. Our AI system demonstrated outstanding performance, achieving an AUC of 0.932 (95% confidence interval (CI) 0.906-0.956) in the internal validation set, 0.903 (0.883-0.922) in the external temporal validation set, 0.923 (0.875-0.961) in the external temporal validation video set, and ranging from 0.855 (0.813-0.894) to 0.971 (0.955-0.985) across seven external geographical validation sets. The diagnostic sensitivity of HOPE AI (85.7%) significantly surpassed that of senior endoscopists (68.0%).</p><p><strong>Conclusions: </strong>HOPE AI exhibited robust diagnostic efficacy and interpretability in H. pylori detection, thereby enhancing the efficiency of diagnosis in routine screening contexts.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry: ChiCTR 2400091317, 2,400,091,720.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"540"},"PeriodicalIF":8.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in frailty, intensive blood pressure treatment, and risks of adverse clinical outcomes: a post hoc analysis of the SPRINT trial.","authors":"Xiaoyun Zhang, Xi Meng, Siyu Wang, Qing Lin, Yueyue Wang, Yu Xiang, Kan Wang, Xuan Zhao, Mian Li, Tiange Wang, Zhiyun Zhao, Jieli Lu, Min Xu, Jie Zheng, Yufang Bi, Yu Xu","doi":"10.1186/s12916-025-04382-7","DOIUrl":"10.1186/s12916-025-04382-7","url":null,"abstract":"<p><strong>Background: </strong>Frailty is becoming a common health issue and its status changes overtime. However, the impact of the frailty status changes on clinical outcomes is unknown. We aimed to evaluate the association between changes in frailty status and adverse clinical outcomes, and to determine whether the changes modify the effects of intensive blood pressure (BP) treatment.</p><p><strong>Methods: </strong>Using frailty index (FI) defined by the Systolic Blood Pressure Intervention Trial (SPRINT), participants were categorized as frail (FI > 0.21) or robust (FI ≤ 0.21). Changes in frailty were evaluated by frailty status at baseline and at 12 months. Participants were categorized as stable-robust, robust-to-frail, frail-to-robust, and stable-frail. Outcomes included incident cardiovascular disease (CVD), all-cause mortality, and serious adverse events (SAEs). Cox proportional hazard models were used to evaluate the association between frailty changes and outcomes, and potential modifications of the changes on intensive BP-lowering treatment.</p><p><strong>Results: </strong>Overall, 7924 eligible SPRINT participants were included. Compared with stable-robust participants, robust-to-frail participants had 70%, 103%, and 47% increased risks of CVD (hazard ratio [HR] = 1.70, 95% confidence interval [CI] 1.20-2.41), all-cause mortality (HR = 2.03, 95% CI 1.22-3.37), and SAEs (HR = 1.47, 95% CI 1.17-1.84), respectively. Compared with stable-frail participants, a 52% decreased risk of all-cause mortality (HR = 0.48, 95% CI 0.24-0.95) was observed in frail-to-robust participants. Changes in frailty did not modify the effects of intensive BP-lowering treatment on CVD, mortality, and SAEs (all P values for interaction > 0.05). In stable-robust participants, intensive BP-lowering treatment was associated with a reduced risk of major CVD events by 41% (HR = 0.59, 95% CI 0.42-0.83), a reduced risk of all-cause mortality by 46% (HR = 0.54, 95% CI 0.31-0.95), and an increased risk of SAEs by 22% (HR = 1.22, 95% CI 1.00-1.48) compared with standard BP-lowering treatment. Similar effects of intensive vs. standard BP-lowering treatment were found in participants with robust-to-frail, frail-to-robust, and stable-frail status.</p><p><strong>Conclusions: </strong>Changes in frailty were associated with changed risks of clinical outcomes. Intensive BP-lowering treatment reduced CVD and mortality regardless of frailty status changes.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"536"},"PeriodicalIF":8.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy, safety, and exploratory biomarker analysis of envafolimab plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer: a prospective, single-arm, phase II trial.","authors":"Xiao Zhao, Jing Zhang, Lupeng Qiu, Quanli Han, Xiang Yan, Yanyun Zhu, Jinliang Wang, Xiaoling Zhang, Shunchang Jiao, Shengjie Sun","doi":"10.1186/s12916-025-04385-4","DOIUrl":"10.1186/s12916-025-04385-4","url":null,"abstract":"<p><strong>Background: </strong>Extensive-stage small cell lung cancer (ES-SCLC) is characterized by a high risk of malignancy and a poor prognosis. This trial aimed to evaluate the efficacy and safety of envafolimab plus chemotherapy as a first-line treatment for ES-SCLC.</p><p><strong>Methods: </strong>This prospective, single-arm, phase II trial was conducted at the Fifth Medical Center of Chinese PLA General Hospital. Eligible patients with histologically or cytologically confirmed ES-SCLC were consecutively enrolled. Patients were given four cycles of carboplatin (area under the curve of 5-6 mg/mL/min, day 1 of each cycle) and etoposide (80-100 mg/m² of body-surface area, on day 1-3 of each cycle) with envafolimab (300 mg, Q3W, day 3 post-chemotherapy of each cycle), followed by envafolimab maintenance until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS).</p><p><strong>Results: </strong>Between October 2021 and November 2022, a total of 32 patients were enrolled in this trial. A total of 32 patients were included in the safety analysis, and 31 patients were included in the efficacy analysis. As of the data cutoff (September 15, 2024), the median follow-up was 27.7 months (IQR, 22.6-NA). The objective response rate (ORR) was 87.1% (95% CI, 70.2-96.4%), and the disease control rate (DCR)was 100% (95% CI, 88.8-100%). The median duration of response (DoR) was 5.47 months (95% CI, 3.43-10 months). The median progression-free survival (PFS) was 6.43 months (95% CI, 4.83-7.67 months), and median overall survival (OS) was 20 months (95% CI, 14.7-NA). Treatment-related adverse events (TRAEs) of any grade were reported in 59.4% of patients, with grade ≥ 3 TRAEs reported in 15.6% of patients. No treatment-related deaths occurred. Additionally, findings from serum proteomic profiling demonstrated that specific immune-related proteins, including CCL3, CXCL10, HGF, and CXCL8, might be correlated with shorter survival and worse clinical outcomes.</p><p><strong>Conclusions: </strong>Envafolimab combined with chemotherapy as a first-line treatment for ES-SCLC yielded favorable clinical efficacy with a manageable safety profile, indicating that it may be a promising treatment modality.</p><p><strong>Trial registration: </strong>This trial was registered at chictr.org.cn (ChiCTR2100044981).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"535"},"PeriodicalIF":8.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in accelerated aging and risk of cardiovascular disease and mortality: three cohort studies.","authors":"Ji-Juan Zhang, Han-Cheng Yu, Ting-Ting Geng, Shuo-Hua Chen, Yu-Xiang Wang, Huan Guo, Xiao-Min Zhang, Mei-An He, Jing-Li Gao, Gang Liu, Yun-Fei Liao, Shou-Ling Wu, An Pan","doi":"10.1186/s12916-025-04365-8","DOIUrl":"10.1186/s12916-025-04365-8","url":null,"abstract":"<p><strong>Background: </strong>Accelerated aging is a dynamic process, yet few studies examined the association of changes in accelerated aging with cardiovascular disease (CVD) and mortality. This study aims to evaluate this association in three prospective cohorts from China and the UK.</p><p><strong>Methods: </strong>Data were drawn from the Kailuan cohort (n = 107,830), the Dongfeng-Tongji (DFTJ) cohort (n = 14,032), and the UK Biobank (n = 316,087). Accelerated aging was assessed by PhenoAge and Klemera-Doubal method (KDM) age, measured at baseline (Kailuan cohort: 2006-2009; DFTJ cohort: 2008-2010; UK Biobank: 2006-2010) and the first follow-up (Kailuan cohort: 2010-2013; DFTJ cohort: 2013; UK Biobank: 2012-2013). Changes in accelerated aging were classified as persistent accelerated aging, recovery from accelerated aging, delayed accelerated aging, and stable non-accelerated aging. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Meta-analysis was performed to summarize estimates across three cohorts.</p><p><strong>Results: </strong>Median follow-up periods were 10.3-15.9 years across three cohorts. When defining accelerated aging by PhenoAge, baseline accelerated aging was significantly associated with increased risks of CVD (pooled HR: 1.41, 95% CI: 1.25, 1.60) and mortality (pooled HR: 1.47, 95% CI: 1.33, 1.63). Compared to participants with persistent accelerated aging, participants recovering from accelerated aging (pooled HR of CVD: 0.76, 95% CI: 0.72, 0.81; pooled HR of mortality: 0.84, 95% CI: 0.78, 0.89), delaying accelerated aging (pooled HR of CVD: 0.75, 95% CI: 0.70, 0.79; pooled HR of mortality: 0.77, 95% CI: 0.72, 0.83) or maintaining non-accelerated aging (pooled HR of CVD: 0.59, 95% CI: 0.48, 0.71; pooled HR of mortality: 0.58, 95% CI: 0.55, 0.62) exhibited decreased risks of both CVD and mortality. When defining accelerated aging by KDM age, the results remained consistent with those of PhenoAge.</p><p><strong>Conclusions: </strong>Accelerated aging is a significant risk factor for CVD and mortality. Recovering from or delaying accelerated aging, or maintaining non-accelerated aging, was associated with reduced risks of CVD and mortality.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"533"},"PeriodicalIF":8.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the causal and independent impact of parity-related reproductive factors on risk of breast cancer subtypes.","authors":"Claire Prince, Laura D Howe, Eleanor Sanderson, Gemma C Sharp, Abigail Fraser, Bethan Lloyd-Lewis, Rebecca C Richmond","doi":"10.1186/s12916-025-04375-6","DOIUrl":"10.1186/s12916-025-04375-6","url":null,"abstract":"<p><strong>Background: </strong>Observational evidence proposes a protective effect of having children and an early first pregnancy on breast cancer development; however, the causality of this association remains uncertain. Here, we assess whether parity-related reproductive factors impact breast cancer risk independently of each other and other causally related or genetically correlated factors: adiposity, age at menarche, and age at menopause.</p><p><strong>Methods: </strong>We used genetic data from UK Biobank for reproductive factors and adiposity, and the Breast Cancer Association Consortium for risk of overall, estrogen receptor (ER) positive and negative breast cancer, and breast cancer subtypes. We applied univariable and multivariable Mendelian randomization (MR) to estimate genetically predicted direct effects of ever parous status, ages at first birth and last birth, and number of births on breast cancer risk.</p><p><strong>Results: </strong>We found limited evidence for a genetically predicted protective effect of an earlier age at first birth on breast cancer risk. While the univariable analysis revealed later age at first birth decreased ER-negative breast cancer risk (odds ratio (OR): 0.76; 95% confidence interval: 0.61, 0.95 per standard deviation (SD) increase in age at first birth), this effect attenuated with separate adjustment for age at menarche (potential confounder) (OR: 0.83; 0.62, 1.06) and age at menopause (genetically correlated factor) (OR: 0.80; 0.66, 1.01). Furthermore, we found evidence that a later age at first birth decreased HER2-enriched breast cancer risk but only after adjusting for number of births (potential mediator) (OR: 0.28; 0.11, 0.57 per SD increase in age at first birth). In the multivariable analysis, we found little evidence for genetically predicted effects of ever-parous status, age at last birth, or number of births on breast cancer risk; however, analyses of ever-parous status and age at last birth were limited by weak instruments.</p><p><strong>Conclusions: </strong>This study found minimal evidence of a genetically predicted protective effect of earlier age at first birth on breast cancer risk, while identifying some evidence for a genetically predicted adverse effect on ER-negative breast cancer risk. However, weak instruments limited the multivariable analysis of ever parous status and age at last birth, which may be improved with larger sample sizes.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"530"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical guidance for conducting high-quality and rapid interim analyses in adaptive clinical trials.","authors":"Helen Mossop, Zoë Walmsley, Nina Wilson, Opeyemi Agbeleye, Michelle Bardgett, Alex Bevin-Nicholls, Matthew Breckons, Michael Cole, Dawn Craig, Munyaradzi Dimairo, Helen Hancock, Martin Law, Andre Lopes, Nurulamin M Noor, Chizoba Oparah, Philip Pallmann, Julia Phillipson, David S Robertson, M Dawn Teare, Katie H Thomson, Christina Yap, James M S Wason","doi":"10.1186/s12916-025-04362-x","DOIUrl":"10.1186/s12916-025-04362-x","url":null,"abstract":"<p><strong>Background: </strong>Adaptive designs are increasingly being used in clinical trials within diverse clinical areas. They can offer advantages over traditional non-adaptive approaches, including improved efficiency and patient benefit. The level of improvement observed in practice depends to a large degree on conducting interim analyses (at which adaptations can be made to the trial based on collected data) rapidly and to a high standard.</p><p><strong>Methods: </strong>The ROBust INterims for adaptive designs (ROBIN) project aimed to identify best practice for conducting high-quality and rapid interim analyses. This was done through evidence synthesis of published work, qualitative research with trial stakeholders working at public sector clinical trials units, engagement with patients and the public, and a meeting of trial stakeholders to discuss findings and agree recommendations.</p><p><strong>Results: </strong>This paper provides recommendations for teams that conduct adaptive trials about how to ensure interim analyses are done rapidly and to a high standard. We break down recommendations by stage of the trial. We also identify a lack of methodology on how best to involve patients in adaptive trials and related decision-making. A limitation of our recommendations is that the research was mostly focused on UK academic settings, although we believe much of the recommendations are relevant in other countries and to industry-sponsored trials.</p><p><strong>Conclusions: </strong>When following the recommendations outlined in this paper, the process of planning and executing interim analyses will be smoother; in turn, this will lead to more benefits from using adaptive designs.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"528"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMI differences on anticoagulation with bivalirudin vs. heparin during primary PCI: a BRIGHT-4 subanalysis.","authors":"Dali Zhang, Yi Li, Miaohan Qiu, Zhenyang Liang, Kai Xu, Yang Li, Guanshan Zhang, Wen Xie, Hesong Zeng, Yucai Cheng, Jidong Liu, Xiang Cheng, Qiutang Zeng, Ke Zhu, Junxing Hu, Kang Cheng, Jingping Wang, Renli Cheng, Yinpin Zhou, Benyun Wang, Guiqiu Cao, Yaling Han, Gregg W Stone","doi":"10.1186/s12916-025-04374-7","DOIUrl":"10.1186/s12916-025-04374-7","url":null,"abstract":"<p><strong>Background: </strong>Body mass index (BMI) is associated with ischemic and bleeding events in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Procedural anticoagulation with bivalirudin followed by a prolonged high-dose post-PCI infusion was shown in the BRIGHT-4 trial to reduce mortality and major bleeding compared with heparin monotherapy. We aimed to assess the outcomes of bivalirudin compared with heparin in relation to BMI in STEMI patients undergoing primary PCI.</p><p><strong>Methods: </strong>This prespecified subgroup analysis from the BRIGHT-4 trial evaluated the treatment effects of bivalirudin with a high-dose infusion for 2-4 h after primary PCI compared with heparin monotherapy in 6,016 randomized STEMI patients undergoing primary PCI predominantly via radial artery access stratified according to baseline BMI. A total of 3284 (54.6%) patients had a BMI < 25 kg/m², the pre-specified stratification threshold.</p><p><strong>Results: </strong>The primary endpoint of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding events at 30 days in all enrolled patients occurred less often in patients with BMI ≥ 25 kg/m² compared with those with BMI < 25 kg/m² [2.9% vs. 4.4%; unadjusted hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.50-0.87; P = 0.003], which was no longer significant after adjusting for confounders (adjusted HR 0.99, 95% CI 0.74-1.31; P = 0.92). Bivalirudin reduced the rate of the primary endpoint compared with heparin in patients with BMI < 25 kg/m² (3.2% vs. 5.7%; adjusted HR 0.56, 95% CI 0.40-0.79) but not in those with BMI ≥ 25 kg/m² (2.9% vs. 2.9%; adjusted HR 0.97, 95% CI 0.62-1.52; P_interaction = 0.04). A similar pattern was observed for the individual components of the primary endpoint, as well as for the composite of all-cause death or BARC types 2-5 bleeding.</p><p><strong>Conclusions: </strong>Anticoagulation with bivalirudin followed by a prolonged high-dose infusion reduced the composite endpoint of all-cause death or BARC types 3-5 bleeding in STEMI patients undergoing primary PCI with lower BMI but not in those with higher BMI compared with heparin monotherapy.</p><p><strong>Trial registration: </strong>The BRIGHT-4 trial is registered with ClinicalTrials.gov (NCT03822975).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"525"},"PeriodicalIF":8.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning-aided optical biopsy achieves whole-chain diagnosis of Correa cascade of gastric cancer: a prospective study.","authors":"Guanqun Liu, Guangchao Li, Zhen Li, Xuejun Shao, Rui Ji, Tian Ma, Yan Zhang, Jingran Su, Qingqing Qi, Jing Guo, Yishan He, Xiaoxiao Yang, Yanqing Li, Xiuli Zuo","doi":"10.1186/s12916-025-04310-9","DOIUrl":"10.1186/s12916-025-04310-9","url":null,"abstract":"<p><strong>Background: </strong>Biopsies are essential in differentiating benign from malignant lesions in routine gastroscopy. Nevertheless, redundant biopsies increase patients' expenses and pathologists' workload. Probe-based confocal laser endomicroscopy (pCLE) enables real-time in vivo histological evaluation for gastric neoplasms and precancerous conditions. However, endoscopists vary widely in skill, and the use of pCLE requires histopathology expertise, which limits its application in nonacademic settings. This study aimed to develop a pCLE computer-aided diagnosis system (CCADS) for real-time whole-chain diagnosis of Correa cascade of gastric cancer and evaluate it in a real clinical setting.</p><p><strong>Methods: </strong>Gastric pCLE images and videos from 5771 examinations were retrospectively collected. CCADS was constructed using deep learning networks. It was developed using 47,462 pCLE images and 461 video segments and evaluated via multistep validation. A total of 11,439 images and 667 videos were identified for offline validation. Consecutive patients from October 2019 to September 2021 were enrolled in a prospective diagnostic study for real-time validation, which included 951 patients in the statistics. Blinded expert endoscopists and CCADS independently performed real-time pCLE diagnosis of gastric mucosal lesions in routine examinations, with double-read histopathology as the gold standard. The real-time diagnostic performance of CCADS was evaluated and compared with that of experts.</p><p><strong>Results: </strong>CCADS achieved high diagnostic performance in image test, video test, and a prospective diagnostic study with a large sample size. Overall, 1254 lesions from 951 patients were included in the prospective test. The real-time diagnostic accuracies of CCADS for inflammation, atrophy, gastric intestinal metaplasia (GIM), low-grade intraepithelial neoplasia (LGIN), and high-grade intraepithelial neoplasia and gastric cancer (HGIN/CA) were 91.71%-97.13%. CCADS achieved high sensitivity (98.44%) and specificity (97.06%) for HGIN/CA. Compared with experts, CCADS achieved similar accuracies in diagnosing atrophy, GIM, and LGIN and similar sensitivities in all five categories. Further, CCADS showed a significantly higher sensitivity (96.70% vs. 89.01%, p = 0.044) for gastric neoplasms (LGIN + HGIN/CA) and reduced the misdiagnosis of neoplasms.</p><p><strong>Conclusions: </strong>CCADS achieved expert-level whole-chain diagnosis of Correa cascade. It could assist endoscopists in improved surveillance of gastric neoplasms and precancerous conditions, promote the application of pCLE, and reduce biopsies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03784209.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"527"},"PeriodicalIF":8.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}