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Confounder adjustment in observational studies investigating multiple risk factors: a methodological study.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-03-05 DOI: 10.1186/s12916-025-03957-8
Yinyan Gao, Linghui Xiang, Hang Yi, Jinlu Song, Dingkui Sun, Boya Xu, Guochao Zhang, Irene Xinyin Wu
{"title":"Confounder adjustment in observational studies investigating multiple risk factors: a methodological study.","authors":"Yinyan Gao, Linghui Xiang, Hang Yi, Jinlu Song, Dingkui Sun, Boya Xu, Guochao Zhang, Irene Xinyin Wu","doi":"10.1186/s12916-025-03957-8","DOIUrl":"10.1186/s12916-025-03957-8","url":null,"abstract":"<p><strong>Background: </strong>Confounder adjustment is critical for accurate causal inference in observational studies. However, the appropriateness of methods for confounder adjustment in studies investigating multiple risk factors, where the factors are not simply mutually confounded, is often overlooked. This study aims to summarise the methods for confounder adjustment and the related issues in studies investigating multiple risk factors.</p><p><strong>Methods: </strong>A methodological study was performed. We searched PubMed from January 2018 to March 2023 to identify cohort and case-control studies investigating multiple risk factors for three chronic diseases (cardiovascular disease, diabetes and dementia). Study selection and data extraction were conducted independently by two reviewers. The study objectives were grouped into two categories: widely exploring potential risk factors and examining specific risk factors. The methods for confounder adjustment were classified based on a summarisation of the included studies, identifying six categories: (1) each risk factor was adjusted for potential confounders separately (the recommended method); (2) all risk factors were mutually adjusted (i.e. including all factors in a multivariable model); (3) all risk factors were adjusted for the same confounders separately; (4) all risk factors were adjusted for the same confounders with some factors being mutually adjusted; (5) all risk factors were adjusted for the same confounders with mutual adjustment among them being unclear; and (6) unable to judge. All data were descriptively analysed.</p><p><strong>Results: </strong>A total of 162 studies were included, with 88 (54.3%) exploring potential risk factors and 74 (45.7%) examining specific risk factors. The current status of confounder adjustment was unsatisfactory: only ten studies (6.2%) used the recommended method, all of which aimed at examining several specific risk factors; in contrast, mutual adjustment was adopted in over 70% of the studies. The remaining studies either adjusted for the same confounders across all risk factors, or unable to judge.</p><p><strong>Conclusions: </strong>There is substantial variation in the methods for confounder adjustment among studies investigating multiple risk factors. Mutual adjustment was the most commonly adopted method, which might lead to overadjustment bias and misleading effect estimates. Future research should avoid indiscriminately including all risk factors in a multivariable model to prevent inappropriate adjustment.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"132"},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555770","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}
引用次数: 0
Cost-effectiveness of universal genetic screening for familial hypercholesterolemia in young adults aged 18-40 years in China. 在中国 18-40 岁青壮年中普及家族性高胆固醇血症基因筛查的成本效益。
IF 7 1区 医学
BMC Medicine Pub Date : 2025-03-05 DOI: 10.1186/s12916-025-03966-7
Rui Meng, Fenghao Shi, Baoming Zhang, Chao Li, Jinyan Wang, Lingqin Song, Lei Zhang, Mingwang Shen
{"title":"Cost-effectiveness of universal genetic screening for familial hypercholesterolemia in young adults aged 18-40 years in China.","authors":"Rui Meng, Fenghao Shi, Baoming Zhang, Chao Li, Jinyan Wang, Lingqin Song, Lei Zhang, Mingwang Shen","doi":"10.1186/s12916-025-03966-7","DOIUrl":"10.1186/s12916-025-03966-7","url":null,"abstract":"<p><strong>Background: </strong>Mortality from familial hypercholesterolemia (FH) remains high due to late diagnosis, and the rate of timely diagnosis remains low (< 10% globally and < 1% in China). Early screening and treatment could significantly reduce mortality risk, especially among young adults. This study aims to evaluate the cost-effectiveness of universal genetic screening of young adults aged 18-40 years compared to universal cholesterol screening or current passive screening strategies (opportunistic cholesterol screening and genetic cascade testing) for FH in China.</p><p><strong>Methods: </strong>A decision-analytic Markov model was constructed to simulate the lifetime (until 100 years old or 99% of patients died) coronary heart disease (CHD) events, discounted costs, gains in quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) of different screening strategies. The model targeted the general population aged 18-40 years (226,869,800 males and 209,030,180 females) from a healthcare provider's perspective. Model parameters were derived from published literatures and the largest nationwide screening program of FH in China. The willingness-to-pay threshold (US$38,042) was chosen as three times the Chinese per-capita gross domestic product (GDP) in 2023. Sensitivity analyses and threshold analyses were conducted to assess the robustness of the results.</p><p><strong>Results: </strong>Universal genetic screening of young adults aged 18-40 years is cost-effective when compared to both current passive screening strategies and universal cholesterol screening. Compared with current passive screening, universal genetic screening could prevent 172,956 CHD events (88,766 non-fatal, 84,191 fatal) with additional costs of US$40.45 billion and gaining additional 1.23 million QALYs, corresponding to an ICER of US$32,960/QALY gained. Implementing universal genetic screening at younger ages would reduce the ICER from US$36,901/QALY to US$28,910/QALY. The model was most sensitive to the cost and sensitivity of genetic testing. If the cost of genetic testing decreased from US$96.50 to US$38.83 or $2.76, universal genetic screening would become very cost-effective or even cost-saving.</p><p><strong>Conclusions: </strong>Universal FH genetic screening in young adults has the potential to be cost-effective in China, compared to current passive screening strategy and universal cholesterol screening strategy. Performing screening in younger age would result in better cost-effectiveness benefit.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"139"},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566186","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}
引用次数: 0
Spatiotemporal heterogeneity in malaria transmission across Indonesia: analysis of routine surveillance data 2010-2019.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-03-05 DOI: 10.1186/s12916-025-03902-9
Bimandra A Djaafara, Ellie Sherrard-Smith, Thomas S Churcher, Sri Budi Fajariyani, Hellen Dewi Prameswari, Herdiana Herdiana, Riskha Tiara Puspadewi, Karina D Lestari, Iqbal R F Elyazar, Patrick G T Walker
{"title":"Spatiotemporal heterogeneity in malaria transmission across Indonesia: analysis of routine surveillance data 2010-2019.","authors":"Bimandra A Djaafara, Ellie Sherrard-Smith, Thomas S Churcher, Sri Budi Fajariyani, Hellen Dewi Prameswari, Herdiana Herdiana, Riskha Tiara Puspadewi, Karina D Lestari, Iqbal R F Elyazar, Patrick G T Walker","doi":"10.1186/s12916-025-03902-9","DOIUrl":"10.1186/s12916-025-03902-9","url":null,"abstract":"<p><strong>Background: </strong>Indonesia faces challenges in achieving its goal of eliminating malaria by 2030, with cases stagnating between 2015 and 2019. This study analysed regional epidemiological trends and demographic changes in malaria cases from 2010 to 2019, considering differences in surveillance across the country.</p><p><strong>Methods: </strong>We analysed national and sub-national malaria routine surveillance data using generalised additive and generalised linear models to assess temporal trends in case reporting, test positivity, demographics, and parasite species distribution while accounting for surveillance variations.</p><p><strong>Results: </strong>After adjusting for increased testing from 2015 onwards, we estimated declining malaria incidence in six of seven Indonesian regions. These regions showed a demographic shift toward older, predominantly male cases, suggesting a transition from household to occupational transmission. In contrast, Papua maintained high transmission with cases concentrated in children. Despite comprising only 2% of Indonesia's population, Papua's contribution to national malaria cases rose from 40 to 90% (2010-2019).</p><p><strong>Conclusion: </strong>While most Indonesian regions progress toward elimination by addressing mobile and migrant populations and P. vivax transmission, Papua shows different patterns with persistently high transmission among children. Achieving nationwide elimination requires enhanced control measures, improved healthcare access, and strengthened multisectoral collaboration to address these region-specific challenges.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"136"},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555890","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}
引用次数: 0
Impact of coronary artery calcium on progression of diastolic dysfunction: a cohort study.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-28 DOI: 10.1186/s12916-025-03956-9
Ki Hong Choi, Danbee Kang, Seung Hun Lee, Darae Kim, Sung Won Cho, Soo-Hee Choi, Taek Kyu Park, Joo Myung Lee, Young Bin Song, Joo-Yong Hahn, Seung-Hyuk Choi, Hyeon-Cheol Gwon, Soo Jin Cho, Jeong Hoon Yang
{"title":"Impact of coronary artery calcium on progression of diastolic dysfunction: a cohort study.","authors":"Ki Hong Choi, Danbee Kang, Seung Hun Lee, Darae Kim, Sung Won Cho, Soo-Hee Choi, Taek Kyu Park, Joo Myung Lee, Young Bin Song, Joo-Yong Hahn, Seung-Hyuk Choi, Hyeon-Cheol Gwon, Soo Jin Cho, Jeong Hoon Yang","doi":"10.1186/s12916-025-03956-9","DOIUrl":"10.1186/s12916-025-03956-9","url":null,"abstract":"<p><strong>Background: </strong>The relationship between coronary artery calcium (CAC) and progression of diastolic dysfunction (DD) during longitudinal follow-up is uncertain. This study aimed to investigate the prevalence and progression of DD according to severity of CAC and understand their synergistic effect on mortality.</p><p><strong>Methods: </strong>This was a population-based cohort study. All 15,193 adults who underwent a health screening exam with simultaneous echocardiography and CAC scan were enrolled. Definite DD (≥ 3/4 abnormal parameters for DD [e', E/e', tricuspid regurgitation velocity, and left atrial volume index]) and definite or probable DD (≥ 2/4) were defined. All-cause mortality was assessed based on the CAC and DD.</p><p><strong>Results: </strong>Among the population, 7995 participants (52.6%) had CAC = 0; 4661 (30.7%) had 0 < CAC < 100; and 2537 (16.7%) had CAC ≥ 100. The prevalence ratios for definite (adjusted ratio: 1.72, 95% CI: 1.23-2.22) and definite or probable DD (adjusted ratio: 1.83, 95% CI: 1.31-2.36) were significantly higher in individuals with CAC ≥ 100 than in those with CAC = 0. There was significant linear association of CAC with E/e' (adjusted p for linearity = 0.001). Compared with CAC < 100 without definite DD, the adjusted HRs with 95% CI for mortality of CAC ≥ 100 without definite DD, CAC < 100 with definite DD, and CAC ≥ 100 with definite DD were 2.56 (95% CI: 1.67-3.94), 3.08 (95% CI: 1.28-7.39), and 3.91 (95% CI: 1.68-9.10). Among participants without DD at CAC measurement who had at least two echocardiographic measurements, the presence of significant CAC (≥ 100) was significantly associated with accelerated progression in definite DD over time (adjusted HR: 1.46, 95% CI: 1.13-1.88), with more rapid elevation of E/e' during follow-up (difference: 0.06, 95% CI: 0.02-0.10, p = 0.003).</p><p><strong>Conclusions: </strong>In the general population, there was a significant relationship between CAC and prevalence of DD, and both subclinical parameters were associated with increased mortality. Moreover, CAC ≥ 100 significantly affects the progression of DD independently of other clinical factors.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"130"},"PeriodicalIF":7.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531103","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}
引用次数: 0
A systematic analysis of temporal trends, characteristics, and citations of retracted stem cell publications.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-28 DOI: 10.1186/s12916-025-03965-8
Fei Song, Binghuo Wu, Gang Wei, Songtao Cheng, Lichao Wei, Wei Xiong, De Luo
{"title":"A systematic analysis of temporal trends, characteristics, and citations of retracted stem cell publications.","authors":"Fei Song, Binghuo Wu, Gang Wei, Songtao Cheng, Lichao Wei, Wei Xiong, De Luo","doi":"10.1186/s12916-025-03965-8","DOIUrl":"10.1186/s12916-025-03965-8","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of retracted publications in stem cell research presents significant challenges to scientific integrity. Although retraction notices are issued, retracted studies continue to be cited, facilitating the dissemination of unreliable findings. This study aimed to systematically explore the characteristics of retracted stem cell publications and evaluate the impact of retractions on subsequent citations.</p><p><strong>Methods: </strong>This study was conducted following the PRISMA guidelines. A comprehensive search of Web of Science, Retraction Watch Database, and PubMed was conducted from their inception through July 25, 2024, to identify retracted stem cell publications. Characteristics including publication details, retraction reasons, and citation counts were extracted. To assess the impact of retraction on subsequent citations, we compared citation patterns between a random sample of retracted papers and matched non-retracted controls from identical journals and issues. Further analysis was conducted to determine whether papers citing retracted articles had an elevated risk of subsequent retraction. Descriptive statistics, chi-squared tests, t-tests, and Mann-Kendall tests were used for data analysis.</p><p><strong>Results: </strong>The systematic search identified 1421 records, with 517 publications meeting inclusion criteria. Temporal analysis revealed two significant trends: an increasing retraction rate that peaked at 0.84% in 2023 and a declining time-to-retraction (median: 30 months, interquartile range: 13-60; Mann-Kendall, tau = - 0.29; P < 0.001). Hospital-affiliated researchers from China contributed to 244 (47.2%) of retractions. Data and image flaws were identified in 360 (69.6%) of retractions. Among 472 Web of Science-indexed retracted publications, 366 (77.5%) accumulated 4884 post-retraction citations, with 114 (24.2%) receiving more citations post-retraction than pre-retraction. Analysis of a random subset of retracted articles (n = 53) demonstrated that only 14 (4.2%) out of 334 post-retraction citations referenced the retraction notice. Compared with 639 non-retracted control publications, retracted articles showed significantly lower post-retraction citation rates (mean rank: 291.32 vs. 351.08; P = 0.01). Moreover, papers citing retracted articles exhibited an 11-fold higher risk of subsequent retraction (odds ratio (OR): 11.09; 95% confidence interval (CI): 7.06-17.43).</p><p><strong>Conclusions: </strong>This analysis reveals substantial research integrity challenges within stem cell research. These findings suggest the necessity for enhanced surveillance mechanisms and standardized protocols to identify and curtail the dissemination of flawed research.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"131"},"PeriodicalIF":7.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531078","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}
引用次数: 0
Global and regional incidence of intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis. 妊娠期肝内胆汁淤积症的全球和地区发病率:系统回顾和荟萃分析。
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-28 DOI: 10.1186/s12916-025-03935-0
Ali Jamshidi Kerachi, Mohammad Amin Shahlaee, Pardis Habibi, Niloofar Dehdari Ebrahimi, Moein Ala, Alireza Sadeghi
{"title":"Global and regional incidence of intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis.","authors":"Ali Jamshidi Kerachi, Mohammad Amin Shahlaee, Pardis Habibi, Niloofar Dehdari Ebrahimi, Moein Ala, Alireza Sadeghi","doi":"10.1186/s12916-025-03935-0","DOIUrl":"10.1186/s12916-025-03935-0","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic cholestasis of pregnancy (ICP) can be a source of significant distress for both pregnant women and the fetus, impairing the quality of life and well-being of pregnant women, leading to psychological disorders among pregnant women with severe or recurrent ICP, and causing life-threatening complications among fetuses. Regrettably, our current understanding of ICP globally is limited, lacking a comprehensive estimation of its incidence. Therefore, in this systematic review and meta-analysis, we aimed to investigate the global and regional incidence of ICP and identify factors that account for its variety across studies.</p><p><strong>Methods: </strong>A comprehensive search strategy was implemented across PubMed, Scopus, and Web of Science databases. To stabilize the variance, the Freeman-Tukey double arcsine transformation was employed. Subgroup analyses were conducted based on continent, publication type, study design and timing, regional classifications, developmental status, and World Bank income grouping. A multivariate meta-regression analysis was performed to estimate the effects of the continuous moderators on the effect size.</p><p><strong>Results: </strong>A total of 42,972,872 pregnant women were analyzed from 302 studies. The overall pooled incidence [95% confidence interval] of ICP was 2.9% [2.5, 3.3]. Studies with larger sample sizes tended to provide significantly lower estimates of ICP incidence: 1.6% [1.3, 2] vs 4.7% [3.9, 5.5]. Asia had the highest incidence of ICP among the continents, whereas Oceania had the lowest. Countries that were classified as developed and with higher income had a lower incidence of ICP than those classified as developing and low and middle income.</p><p><strong>Conclusions: </strong>The findings of this study will provide valuable insights into the current knowledge regarding the association of the quality of public health and socioeconomic variations with the incidence of ICP on a global scale.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"129"},"PeriodicalIF":7.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531100","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}
引用次数: 0
Non-invasive diagnosis of vulvar dysplasia using cervical methylation markers-a case control study.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-28 DOI: 10.1186/s12916-025-03954-x
Sabeth Becker, Lena Dübbel, Dana Behrens, Kristin Knoll, Juliane Hippe, Karin Loser, Eduard Malik, Meike Schild-Suhren
{"title":"Non-invasive diagnosis of vulvar dysplasia using cervical methylation markers-a case control study.","authors":"Sabeth Becker, Lena Dübbel, Dana Behrens, Kristin Knoll, Juliane Hippe, Karin Loser, Eduard Malik, Meike Schild-Suhren","doi":"10.1186/s12916-025-03954-x","DOIUrl":"10.1186/s12916-025-03954-x","url":null,"abstract":"<p><strong>Background: </strong>Diagnostic screenings for vulvar squamous intraepithelial lesions (VSIL) are limited and without information on disease trends. A panel of six methylation markers (ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671; GynTect® assay) has shown promise in diagnosing cervical intraepithelial neoplasia (CIN). Given the similarities between the carcinogenesis of cervix and vulva, this study aimed to investigate the suitability of these markers for diagnosing vulvar lesions.</p><p><strong>Methods: </strong>One hundred twenty-one vulvar FFPE samples and 237 vulvar cell smears with different VSIL grades, HPV status, and with or without lichen sclerosus and planus were tested. Additionally, dysplasia-free vulvar cell smears from patients with cervical dysplasia were analyzed. The expression of DNA methyltransferases (DNMTs) in the FFPE samples was measured.</p><p><strong>Results: </strong>The markers demonstrated high specificity in vulvar smears, with sole 5.45% of dysplasia-free smears testing positive. Yet, 75.00% of vulvar carcinoma smears appear positive in the methylation kit, similar to VHSIL (VIN III) smears with 77.78%. In FFPE samples, dysplasia-free samples from the tumor microenvironment of high-grade vulvar neoplasia showed 43.75% positivity. The positivity rates for VSIL and carcinoma samples were 76.92%, 64.71%, 64.71%, and 80.49%, respectively. DNMT3a expression was the highest in VLSIL (VIN I) samples, while DNMT1 was only expressed in VHSIL (VIN III) and carcinoma samples. Lichen sclerosis and planus showed a high false positive rate of 45.45% for dysplasia-free and 54.54% for smears with dVIN. Cervical HSIL was associated with a significantly higher number of positive results in the kit than in patients without cervical dysplasia.</p><p><strong>Conclusions: </strong>The findings suggest that the methylation markers comprising GynTect® may be suitable for detecting vulvar neoplasia, as they exhibit high sensitivity. Nonetheless, adjustments are needed for comparable specificity. Lichen should be considered in result interpretation, and the kit should be used with caution for patients with lichen. Moreover, we observed methylation changes as an early event with the highest positivity of VLSIL. Surprisingly, changes in methylation pattern are not as local as presumed. Cervical SIL led to changed methylation in the vulva. Patients with positive kit results should be monitored regularly for all genital dysplasia. This sheds new light on the epigenetics in cancer.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"128"},"PeriodicalIF":7.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531184","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}
引用次数: 0
Accelerometer-measured physical activity, frailty, and all-cause mortality and life expectancy among middle-aged and older adults: a UK Biobank longitudinal study.
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-27 DOI: 10.1186/s12916-025-03960-z
Yang Yang, Liangkai Chen, Filippos T Filippidis
{"title":"Accelerometer-measured physical activity, frailty, and all-cause mortality and life expectancy among middle-aged and older adults: a UK Biobank longitudinal study.","authors":"Yang Yang, Liangkai Chen, Filippos T Filippidis","doi":"10.1186/s12916-025-03960-z","DOIUrl":"10.1186/s12916-025-03960-z","url":null,"abstract":"<p><strong>Background: </strong>Physical activity (PA) is associated with reduced frailty and lower mortality rates among middle-aged and older adults. However, the extent to which total PA volume and specific PA intensities are associated with mortality risk across frailty status remains unclear. We aimed to investigate the interactive effects of accelerometer-measured PA with frailty on all-cause mortality and life expectancy.</p><p><strong>Methods: </strong>A total of 78,508 participants were sourced from the UK Biobank for analysis. Frailty index (FI) was used to assess frailty status. Physical activity and sedentary behavior were quantified through accelerometer measurements, capturing the total volume of physical activity (TVPA), moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), and sedentary time (ST). Cox proportional hazard models were applied to calculate adjusted hazard ratios (HRs) and predict life expectancy.</p><p><strong>Results: </strong>During a median follow-up of 6.9 years, 2618 deaths (2.9%) were identified. Compared with robust and physically active counterparts, individuals characterized by frailty, combined with the lowest levels of TVPA (HR 3.05, 95% CI: 2.50-3.71), MVPA (HR 2.65, 95% CI: 2.19-3.21), LPA (HR 2.26; 95% CI: 1.81-2.83), or the highest level of ST (HR 2.08, 95% CI: 1.66-2.61), were found to have the greatest risk of all-cause mortality after comprehensive adjustment. The dose-response relationship, assessed using restricted cubic splines, consistently demonstrated that regardless of frailty categories, higher levels of TVPA, MVPA, and LPA were associated with lower mortality risks, while higher ST level was associated with increased risk. Notably, across the frailty spectrum, individuals in the low tertile of TVPA, MVPA, and LPA, or the top tertile of ST, were associated with reduced life expectancy, with this pattern being more pronounced among frail men compared to frail women.</p><p><strong>Conclusions: </strong>Our findings highlighted the importance of increasing total PA volume, emphasizing MVPA and LPA, and reducing ST across the frailty spectrum to improve life expectancy.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"125"},"PeriodicalIF":7.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522270","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}
引用次数: 0
Development of an artificial intelligence-based multimodal diagnostic system for early detection of biliary atresia. 开发基于人工智能的多模式诊断系统,用于早期检测胆道闭锁。
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-27 DOI: 10.1186/s12916-025-03962-x
Ya Ma, Yuancheng Yang, Yuxin Du, Luyang Jin, Baoyu Liang, Yuqi Zhang, Yedi Wang, Luyu Liu, Zijian Zhang, Zelong Jin, Zhimin Qiu, Mao Ye, Zhengrong Wang, Chao Tong
{"title":"Development of an artificial intelligence-based multimodal diagnostic system for early detection of biliary atresia.","authors":"Ya Ma, Yuancheng Yang, Yuxin Du, Luyang Jin, Baoyu Liang, Yuqi Zhang, Yedi Wang, Luyu Liu, Zijian Zhang, Zelong Jin, Zhimin Qiu, Mao Ye, Zhengrong Wang, Chao Tong","doi":"10.1186/s12916-025-03962-x","DOIUrl":"10.1186/s12916-025-03962-x","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis of biliary atresia (BA) is crucial for improving patient outcomes, yet remains a significant global challenge. This challenge may be ameliorated through the application of artificial intelligence (AI). Despite the promise of AI in medical diagnostics, its application to multimodal BA data has not yet achieved substantial breakthroughs. This study aims to leverage diverse data sources and formats to develop an intelligent diagnostic system for BA.</p><p><strong>Methods: </strong>We constructed the largest known multimodal BA dataset, comprising ultrasound images, clinical data, and laboratory results. Using this dataset, we developed a novel deep learning model and simplified it using easily obtainable data, eliminating the need for blood samples. The models were externally validated in a prospective study. We compared the performance of our model with human experts of varying expertise levels and evaluated the AI system's potential to enhance its diagnostic accuracy.</p><p><strong>Results: </strong>The retrospective study included 1579 participants. The multimodal model achieved an AUC of 0.9870 on the internal test set, outperforming human experts. The simplified model yielded an AUC of 0.9799. In the prospective study's external test set of 171 cases, the multimodal model achieved an AUC of 0.9740, comparable to that of a radiologist with over 10 years of experience (AUC = 0.9766). For less experienced radiologists, the AI-assisted diagnostic AUC improved from 0.6667 to 0.9006.</p><p><strong>Conclusions: </strong>This AI-based screening application effectively facilitates early diagnosis of BA and serves as a valuable reference for addressing common challenges in rare diseases. The model's high accuracy and its ability to enhance the diagnostic performance of human experts underscore its potential for significant clinical impact.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"127"},"PeriodicalIF":7.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522297","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}
引用次数: 0
Induction chemotherapy plus camrelizumab combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma in non-endemic areas: a phase 2 clinical trial in North China. 非流行区局部晚期鼻咽癌诱导化疗+坎瑞珠单抗联合同期放化疗:华北地区2期临床试验。
IF 7 1区 医学
BMC Medicine Pub Date : 2025-02-27 DOI: 10.1186/s12916-025-03964-9
Zhongqiu Wang, Yao Sun, Qingxin Wang, Yanlan Chai, Jian Sun, Ximei Zhang, Qi Wang, Wei Wang, Peiguo Wang
{"title":"Induction chemotherapy plus camrelizumab combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma in non-endemic areas: a phase 2 clinical trial in North China.","authors":"Zhongqiu Wang, Yao Sun, Qingxin Wang, Yanlan Chai, Jian Sun, Ximei Zhang, Qi Wang, Wei Wang, Peiguo Wang","doi":"10.1186/s12916-025-03964-9","DOIUrl":"10.1186/s12916-025-03964-9","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has been confirmed efficient in recurrent or metastatic nasopharyngeal carcinoma (NPC), but its role in the locoregionally advanced setting is undetermined. Previous evidence in non-endemic areas of NPC is also lacking. This study evaluated the efficacy and safety of induction chemotherapy plus camrelizumab followed by concurrent chemoradiotherapy (CCRT) for patients with locoregionally advanced NPC in non-endemic areas.</p><p><strong>Methods: </strong>In this phase 2 trial, patients born and living in North China with untreated stage III to IVa NPC were enrolled. All patients received two 21-day cycles of camrelizumab (200 mg) plus docetaxel (75 mg/m<sup>2</sup>) and cisplatin (75 mg/m<sup>2</sup>), followed by intensity modulated radiotherapy and concurrent cisplatin (80 mg/m<sup>2</sup> for two 21-day cycles). After CCRT, patients received camrelizumab maintenance for 12 cycles. The primary endpoint was 3-year disease-free survival (DFS) rate.</p><p><strong>Results: </strong>From February 2021 to September 2023, a total of 57 patients were included for analysis. The objective response rate was 92.8% after induction therapy and 100% after CCRT. With a median follow-up time of 21 months, the 3-year DFS rate was 84%. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 95.8%, 90.9%, and 89.5%, respectively. The most common grade 3 or 4 treatment-related adverse events were leukopenia and neutropenia during induction therapy, and weight loss and lymphopenia during CCRT.</p><p><strong>Conclusions: </strong>Induction immunochemotherapy combined with CCRT shows promising antitumor activity with a manageable safety profile in patients with locoregionally advanced NPC from non-endemic areas, which deserves further validation.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04782765.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"126"},"PeriodicalIF":7.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522301","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}
引用次数: 0
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