BMC Medicine最新文献

{"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}

{"title":"Physical, cognitive, and mental health impacts of Omicron reinfection in patients with original SARS-CoV-2 infection: a community-based observational study.","authors":"Sizhen Su, Zhendong Jiang, Le Shi, Xiaoxing Liu, Zhibo Zhang, Huan Mei, Nan Gao, Shuilin Wu, Mingzhe Li, Xiong Zhang, Aijun Zhang, Chunlian Tang, Yongbo Zheng, Yimiao Zhao, Na Zeng, Shuyu Ni, Wei Yan, Kai Yuan, Yankun Sun, Yi Hong, Yu Lu, Jie Shi, Yanping Bao, Xiangyou Li, Lin Lu","doi":"10.1186/s12916-025-04322-5","DOIUrl":"10.1186/s12916-025-04322-5","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological and clinical evidence suggests that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reinfection is a complication in a proportion of patients reporting ongoing health issues. However, most studies in the field of SARS-CoV-2 reinfection have focused only on self-reported symptoms and lacked long-term objective measurements. This study aimed to estimate the pattern of chronic symptoms of Omicron reinfection in patients with original SARS-CoV-2 infection by comprehensively assessments 3 years after recovery.</p><p><strong>Methods: </strong>This community-based observational study was conducted in Wuhan, China, between January and April in 2023. All participants were recruited from community and invited to participate the interview and examination in a hospital. The subjective multi-system symptoms were self-reported. The objective radiological features and laboratory data were assessed by measuring blood inflammation and performing chest computed tomography (CT) and pulse oxygen saturation.</p><p><strong>Results: </strong>Among 1438 individuals who participated in the study, 144 were infected with the original variant only in 2020, 980 were Omicron-infected in 2023, 215 were reinfected both in 2020 and 2023, and 99 were never infected. Compared with the non-infection group, the reinfection (odds ratio (OR), 5.15 [95% confidence intervals (CIs), 2.96-8.96]) group was associated with the highest risk of any of chronic physical symptoms, followed by the Omicron infection (3.45 [2.19-5.44]) and original variant infection (2.90 [1.63-5.15]) groups. Compared with the non-infection group, the reinfection (4.05 [2.30-7.14]), Omicron infection (3.72 [2.26-6.11]), and original variant infection (2.71 [1.48-4.95]) groups were associated with an increased risk of any of chronic mental symptoms. Moreover, of all groups, the reinfection group reported the highest seropositivity rate for C-reactive protein, and the highest prevalence rates of ground glass opacities on chest CT and hypoxaemia.</p><p><strong>Conclusions: </strong>Our results suggest that reinfection may be a risk factor for long COVID conditions. These findings provide information for the clinical management and healthcare services of long COVID and SARS-CoV-2 reinfection and highlight the importance taking necessary action to prepare for a future pandemic. The long-term follow-up will be needed to verify the impact of different SARS-CoV-2 infection status on long COVID in the future.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"526"},"PeriodicalIF":8.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198398","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 smartphone dependence and depressive and anxiety symptoms among Chinese adolescents.","authors":"Yanzhi Li, Yi-Fan Lin, Herui Wu, Liwen Yang, Liwan Zhu, Xinchang Sun, Shuwen Dong, Wanxin Wang, Lei Yang, Bin Yan, Ciyong Lu","doi":"10.1186/s12916-025-04372-9","DOIUrl":"10.1186/s12916-025-04372-9","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have examined the associations of baseline smartphone dependence (SPD) with depressive symptoms and anxiety symptoms, ignoring changes in SPD over time. Especially, it is unclear whether individuals quitting SPD remain at high risk for depressive symptoms and anxiety symptoms. This study aimed to investigate the longitudinal associations of changes in SPD with depressive symptoms and anxiety symptoms among adolescents.</p><p><strong>Methods: </strong>From September to December 2021 (wave 1), we recruited adolescents in grades 4 and 7 in five public primary schools and nine public junior high schools in Shenzhen, China, and collected information on SPD using the Smartphone Addiction Scale-Short Version. The cut-off values of ≥ 31 and ≥ 33 were used in boys and girls, respectively, to identify adolescents with SPD. From September to December 2022 (wave 2), in addition to SPD, we collected the information on depressive symptoms and anxiety symptoms using the 9-item version of Patient Health Questionnaire and the 7-item version of General Anxiety Disorder Scale, respectively. The cut-off values for clinically significant symptoms were both ≥ 10. Four patterns of changes in SPD during waves 1-2 were defined: none, quitting, new-onset, and persistent. From September to December 2023 (wave 3), we assessed depressive symptoms and anxiety symptoms again.</p><p><strong>Results: </strong>Of the 3088 adolescents included, the mean age was 12.5 (standard deviation [SD], 1.4) years and 54.3% were boys. Compared with adolescents without SPD, those with new-onset SPD (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.06 to 2.31) or persistent SPD (OR, 2.37; 95% CI, 1.56 to 3.61) showed a higher risk of depressive symptoms, but those quitting SPD did not (OR, 1.33; 95% CI, 0.83 to 2.12). We have observed a similar association between changes in SPD and anxiety symptoms. Several sensitivity analyses confirmed the robustness of the results.</p><p><strong>Conclusions: </strong>Our findings suggest that adolescents with SPD might be a high-risk group for depressive symptoms and anxiety symptoms, and quitting SPD might help prevent them from developing depressive symptoms and anxiety symptoms.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"523"},"PeriodicalIF":8.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198426","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":"Immediate and delayed switches to tenofovir DF-containing, ainuovirine-based antiretroviral regimen: the SPRINT extensional study.","authors":"Fujie Zhang, Weiping Cai, Hao Wu, Ping Ma, Qingxia Zhao, Hongxia Wei, Hongzhou Lu, Hui Wang, Shenghua He, Zhu Chen, Yaokai Chen, Min Wang, Xinming Yun, Ziyue Zhou, Heliang Fu, Hong Qin","doi":"10.1186/s12916-025-04376-5","DOIUrl":"10.1186/s12916-025-04376-5","url":null,"abstract":"<p><strong>Background: </strong>Ainuovirine (ANV) is a new-generation nonnucleoside reverse transcriptase inhibitor with potent antiviral activity and favorable neuropsychiatric and cardiometabolic safety. The SPRINT study showed that switching to fixed-dose ANV combined with lamivudine and tenofovir DF (ANV/3TC/TDF) provided non-inferior virologic efficacy and improved cardiometabolic conditions in virologically suppressed people living with HIV (PLWH) compared to that to cobicistat-boosted elvitegravir plus emtricitabine and tenofovir alafenamide (E/C/F/TAF) at 48 weeks.</p><p><strong>Methods: </strong>In the base study (weeks 0-48), eligible virologically suppressed PLWH (n = 762) were randomized to receive ANV/3TC/TDF or E/C/F/TAF in a double-blind manner. In the extensional study (weeks 48-96), eligible participants on ANV/3TC/TDF continued the assigned regimen (immediate switch group, ISG), while those on E/C/F/TAF re-switched to ANV/3TC/TDF (delayed switch group, DSG). The original E/C/F/TAF group (weeks 0-48) was used as comparator for efficacy analysis. The primary efficacy endpoint was the proportion of PLWH with HIV RNA titer ≥ 50 copies/mL at week 96. Safety outcomes of primary interest included Changes in body weight and fasting serum lipids from weeks 48 to 96.</p><p><strong>Results: </strong>The primary efficacy endpoints were both 3.4% with ISG and DSG at week 96, non-inferior to 1.6% for comparator at week 48. Estimated treatment differences were 1.8% (95% confidence interval [CI] - 0.5 to 4.3%) with ISG versus comparator and 1.9% (95%CI - 0.4 to 4.4%) with DSG versus comparator, respectively. Non-inferiority was established for both ISG and DSG as the upper limits of 95%CI were both below the prespecified margin of 5%. The treatment-emergent adverse events were generally similar between the two switch groups. DSG showed modest reduction in body weight (mean, - 0.59 kg), in contrast to ISG with a minimal weight loss (- 0.03 kg; DSG versus ISG, - 0.56 kg, [- 1.07 to - 0.05]). Fasting serum low-density lipoprotein cholesterol remained generally unchanged in ISG (0.01 mmol/L) but improved greatly in DSG at week 96 from week 48 (- 0.30 mmol/L; - 0.31 mmol/L [- 0.47 to - 0.16]).</p><p><strong>Conclusions: </strong>Both ISG and DSG maintained high viral Suppression in PLWH through 96 weeks. DSG could offset weight gain and dyslipidemia associated with previous exposure to E/C/F/TAF.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Register number, ChiCTR2100051605.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"524"},"PeriodicalIF":8.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198409","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":"Gaps in the global health research landscape for mpox: an analysis of research activities and existing evidence.","authors":"Rodrigo Furst, Emilia Antonio, Marieke de Swart, Isabel Foster, Johannes Paolo Cerrado, Zaharat Kadri-Alabi, Susan Khader Ibrahim, Lauren Ashley, Duduzile Ndwandwe, Louise Sigfrid, Alice Norton","doi":"10.1186/s12916-025-04350-1","DOIUrl":"10.1186/s12916-025-04350-1","url":null,"abstract":"<p><strong>Background: </strong>Since December 2022, human cases of mpox in the Democratic Republic of the Congo (DRC) have risen at unprecedented rates. We identified a need for systematic mapping of the active research landscape and evidence, assessing their alignment with both local and global research priorities, to inform urgently needed research investments to support response efforts.</p><p><strong>Methods: </strong>We conducted a mapping review of global research funding and international clinical trial registries and established a systematic rapid research needs appraisals platform to identify existing evidence gaps on mpox research. We analysed the alignment of these to established research categories and both local and globally identified mpox-specific research priorities.</p><p><strong>Results: </strong>We identified 124 ongoing mpox research grants, 79 registered trials and 415 published studies. Most grants (85.0%, n = 105/124), clinical trials (49.3%, n = 39/79) and primary studies (57.7%, n = 205/355) were conducted in high-income countries, with most evidence published in response to the 2022 clade II global mpox outbreaks. Research funding has been focussed on vaccine and therapeutic pre-clinical development. Key gaps remain in both ongoing research and evidence relating to clinical characterisation among populations at risk, clinical trials on effective medical countermeasures specific to clade I, social sciences, health systems research, and healthcare and community protection.</p><p><strong>Conclusions: </strong>Our findings highlight persistent research gaps related to mpox clade Ib, particularly the limited knowledge on its characteristics and a lack of ongoing efforts to develop effective medical countermeasures, posing a risk to control efforts. Aligning research and investments to locally and globally identified research priorities and evidence gaps will help support national, regional and international responses to prevent transmission and improve outcomes.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"522"},"PeriodicalIF":8.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191244","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":"Multidisciplinary team for antithrombotics management and clinical outcomes in older adults with atrial fibrillation: a target trial emulation.","authors":"Maïwenn Prunel, Alexis Cochard, Leila Abbas, Elodie Baudry, Eric Pautas, Nicolas Legris, Patrick Assayag, Corinne Frere, Marc Verny, Noémie Simon-Tillaux, Lorene Zerah","doi":"10.1186/s12916-025-04291-9","DOIUrl":"10.1186/s12916-025-04291-9","url":null,"abstract":"<p><strong>Background: </strong>Recent international guidelines emphasize a multidisciplinary, patient-centered approach to managing atrial fibrillation (AF), particularly regarding antithrombotic (antiplatelet and anticoagulant) management. These guidelines advocate establishing multidisciplinary AF teams, but the clinical benefits of this approach for high-risk, clinically complex subgroups-particularly among very old and frail patients-remain uncertain. Our objective was to evaluate the impact of a hospital multidisciplinary team meeting dedicated to antithrombotics management on a composite measure of all-cause death, major thromboembolic events, or major or clinically relevant bleeding within 6 months in older adults with AF.</p><p><strong>Methods: </strong>A prospective multicenter cohort study was conducted in five acute geriatric departments in the Paris area between May 2021 and January 2024. Using a target trial emulation approach (cloning, censoring, weighting strategies), outcomes were analyzed in patients aged ≥ 75 years with AF or atrial flutter, followed in the geriatric departments (via outpatient consultation or hospitalization; > 98% were hospitalized). Participants were followed for 6 months or until death. The primary exposure was a hospital multidisciplinary team meeting within 45 days of inclusion, involving geriatricians, cardiologists, neurovascular specialists, and hemostasis experts. Cumulative incidences were estimated using the reverse Kaplan-Meier method.  RESULTS: The study included 818 patients, 138 (16.9%) in the hospital multidisciplinary-team meeting arm (median age 89 (Q1Q3 84-93), 57% female). The 6-month cumulative incidence of the primary composite outcome was 35.3% (95% CI, 29.6 to 41.8) in the multidisciplinary-team meeting arm and 36.2% (95% CI, 32.2 to 40.1) in the control arm (risk difference - 0.9 (95% CI, - 7.5 to 6.0); p = .79). The 2 arms did not differ in individual events within the composite measure.</p><p><strong>Conclusions: </strong>A hospital multidisciplinary team meeting dedicated to antithrombotics management in older adults with AF was not associated with a reduction in all-cause death, major thromboembolic events, or major or clinically relevant bleeding within 6 months. These findings should be interpreted with caution due to the observational design and potential for residual confounding.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov registration: NCT04932603.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"521"},"PeriodicalIF":8.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191246","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":"The brief resilience scale: a genome-wide association study in the UK Biobank.","authors":"Marilyn C Cornelis, John A Caldwell, Thanh Huyen T Vu, Stephen R Hennigar, Claire E Berryman, Harris R Lieberman","doi":"10.1186/s12916-025-04368-5","DOIUrl":"10.1186/s12916-025-04368-5","url":null,"abstract":"<p><strong>Background: </strong>Some individuals exposed to traumatic stressors develop psychiatric disorders while others remain resilient. The Brief Resilience Scale (BRS) assesses the ability to \"bounce back\" from stress and is a widely used measure of trait resilience. We performed the first genome-wide association study of BRS in the UK Biobank (UKB).</p><p><strong>Methods: </strong>Beginning 2022, a subset of UKB participants completed an on-line mental-health questionnaire that included the six-item BRS. BRS data and genome-wide typing and imputation were available for 124,774 participants of European ancestry. Genome-wide linear tests of BRS were performed, followed by SNP-based heritability and cross-trait genetic correlation analyses. Nominally significant loci (P < 5 × 10^-6) were followed up for candidate gene mapping.</p><p><strong>Results: </strong>SNP-based heritability of BRS was 7.3% and strong genetic correlations (r_g) were observed with neuroticism (r_g, - 0.70 to - 0.44), depression (r_g, - 0.63 to - 0.37) and anxiety (r_g, - 0.81 to - 0.46). Three loci met genome-wide significance (P < 5 × 10^-8, near VRK2, TNKS/MSRA and RAB36) and 29 loci met nominal significance (P < 5 × 10^-6). None of these were replicated in prior GWAS using different measures of resilience. The strongest candidate genes prioritized on the basis of both functional and biological evidence include VRK2 (2p16.1) (previously associated with neuropsychiatric disorders) and MSRA (8p23.1) (reduces methionine sulfoxide to methionine). Others at nominally significant loci include SLC6A9 (1p34.1) (encodes a glycine transporter), NPY (7p15.2) (involved in stress response), CADPS2 (7q31.32) (involved in synaptic vesicle exocytosis), and PCDH9 (13q21.32) (involved in neural tissue cell adhesion).  CONCLUSIONS: Our findings provide further support for a genetic basis to trait resilience and one shared with psychiatric disorders and personality traits including depression, anxiety, and neuroticism. Our promising loci warrant replication but offer new biological insight to resilience.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"520"},"PeriodicalIF":8.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173853","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":"Long-term psychological effects of COVID-19-related quarantine: an observational study of three cohorts in Norway and Iceland.","authors":"Li Lu, Yue Wang, Omid V Ebrahimi, Qing Shen, Anna Bára Unnarsdóttir, Arna Hauksdóttir, Asle Hoffart, Edda Bjork Thordardottir, Ingibjörg Magnúsdóttir, Jóhanna Jakobsdóttir, Lill Trogstad, Thor Aspelund, Fang Fang, Ragnhild E Brandlistuen, Sverre Urnes Johnson, Unnur Anna Valdimarsdóttir, Ole A Andreassen, Helga Ask","doi":"10.1186/s12916-025-04349-8","DOIUrl":"10.1186/s12916-025-04349-8","url":null,"abstract":"<p><strong>Background: </strong>Longitudinal assessments of psychological effects related to length and recency of quarantine experience in general populations are of importance. We aim to investigate if recency and duration of quarantine exposures during the COVID-19 pandemic were associated with mental health, across subgroups.</p><p><strong>Methods: </strong>We included three prospective cohorts from Iceland and Norway with data on quarantine and symptoms of depression and anxiety from March 2020 to March 2022. We calculated prevalence ratios (PR) of probable depression and anxiety in relation to quarantine exposure, and performed longitudinal analyses in a subpopulation with repeated assessments to test the potential change in mental health burden due to quarantine over time while controlling for current quarantine status and other covariates.</p><p><strong>Results: </strong>In total, 105,344 and 94,435 individuals were included in the analysis of probable depression and anxiety, respectively, with 18.2% and 40.0% reporting quarantine exposure before the most recent assessment of corresponding mental health symptoms. Overall, quarantine exposure was associated with probable depression (PR 1.19 [95% CI: 0.99-1.42]) and anxiety (PR 1.21 [1.08-1.36]). Compared to individuals without quarantine, being exposed to quarantine for 0-2, 2-4, or > 4 weeks was associated with incrementally higher prevalence of probable depression (PR 1.15 [0.93-1.43]; 1.34 [1.06-1.68]; 1.72 [1.35-2.18], respectively) and probable anxiety (PR 1.12 [1.01-1.23]; 1.28 [1.14-1.45]; 1.76 [1.56-1.98]) in a step-wise manner; those who were quarantined within the last 2 weeks, last 2-4 weeks, or earlier showed a higher prevalence of probable depression in a dose-response manner (PR 1.62 [1.32-1.99], 1.32 [1.07-1.63], and 1.23 [1.06-1.43], respectively). The prevalence of probable anxiety did not appear to differ by the recency of quarantine. The longitudinal analyses (mean follow-up: 20.5 months) confirmed significantly higher prevalence of probable depression but only among those who were quarantined for > 4 weeks (PR 1.61 [1.30-2.00]), and of probable anxiety among those quarantined 2-4 weeks (PR 1.29 [1.14-1.45]) and > 4 weeks (PR 1.56 [1.34-1.82]).</p><p><strong>Conclusions: </strong>This study underscores the importance of monitoring mental well-being of populations recently quarantined, particularly those quarantined for prolonged periods. Greater emphasis should be placed on the detrimental psychological effects in the risk-cost-benefit analysis of quarantine as a mitigation strategy in future pandemics.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"519"},"PeriodicalIF":8.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147818","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}