European Journal of Epidemiology最新文献

{"title":"Machine-learning approaches to predict individualized treatment effect using a randomized controlled trial","authors":"Rikuta Hamaya, Konan Hara, JoAnn E. Manson, Eric B. Rimm, Frank M. Sacks, Qiaochu Xue, Lu Qi, Nancy R. Cook","doi":"10.1007/s10654-024-01185-7","DOIUrl":"https://doi.org/10.1007/s10654-024-01185-7","url":null,"abstract":"<p>Recent advancements in machine learning (ML) for analyzing heterogeneous treatment effects (HTE) are gaining prominence within the medical and epidemiological communities, offering potential breakthroughs in the realm of precision medicine by enabling the prediction of individual responses to treatments. This paper introduces the methodological frameworks used to study HTEs, particularly based on a single randomized controlled trial (RCT). We focus on methods to estimate conditional average treatment effect (CATE) for multiple covariates, aiming to predict individualized treatment effects. We explore a range of methodologies from basic frameworks like the T-learner, S-learner, and Causal Forest, to more advanced ones such as the DR-learner and R-learner, as well as cross-validation for CATE estimation to enhance statistical efficiency by estimating CATE for all RCT participants. We also provide a practical application of these approaches using the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, which compared the effects of high versus low-fat diet interventions on 2-year weight changes. We compared different sets of covariates for CATE estimation, showing that the DR- and R-learners are useful for the estimation of CATE in high-dimensional settings. This paper aims to explain the theoretical underpinnings and methodological nuances of ML-based HTE analysis without relying on technical jargon, making these concepts more accessible to the clinical and epidemiological research communities.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"8 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 1001 nights-cohort – paving the way for future research on working hours, night work, circadian disruption, sleep, and health","authors":"Kirsten Nabe-Nielsen, Anne Emily Saunte Fiehn Arup, Mette Sallerup, Rikke Harmsen, Anna Sofie Ginty, Marie Tolver Nielsen, Anne-Sofie Rosenfeldt Jensen, Anders Aagaard, Vivi Schlünssen, Ann Dyreborg Larsen, Anne Helene Garde","doi":"10.1007/s10654-025-01201-4","DOIUrl":"https://doi.org/10.1007/s10654-025-01201-4","url":null,"abstract":"<p>Night work and circadian disruption are linked to major public health challenges, e.g. cancer, cardiometabolic disease, and accidents. We established the <i>1001 nights-cohort</i> to explore mechanisms underlying health effects of night work and circadian disruption. 1075 female hospital employees participated from September 2022 to April 2024. The data collection included a questionnaire, a blood sample, anthropometric measures, and sleep actigraphy and sleep diaries across 14 days. In subsamples, light exposure, physical activity, skin temperature, and blood glucose were measured continuously for 7 days, and saliva samples were collected five times across one day. The cohort consists of 2- and 3-shift workers with night work (66%), permanent night workers (7%), permanent evening workers or 2-shift workers without night work (9%), and permanent day workers (18%). Data comprise 4553 day shifts, 997 evening shifts, 1963 night shifts, and 6458 days without work. The poorest health was observed among permanent night workers and the group of shift workers <i>without</i> night work. The 1001 nights-cohort is the most comprehensive data within night work and working hour research due to the combination of questionnaires, biomarkers, technical measurements, and possibilities for linkage to historical and future register-based information about working hours from the Danish Working Hour Database (DAD) and diagnoses. With its repeated measurements within the same individual, the cohort will advance research on physiological and behavioral mechanisms underlying health effects of working hours, night work, and circadian disruption and deliver important scientific input for updating guidelines on healthy scheduling of working hours.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"26 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cohort profile: The BiCoVac cohort - a nationwide Danish cohort to assess short and long-term symptoms following COVID-19 vaccination","authors":"Christina Bisgaard Jensen, Kristoffer Torp Hansen, Casper Mailund Nielsen, Stefan Nygaard Hansen, Henrik Nielsen, Charlotte Ulrikka Rask, Per Fink, Thomas Meinertz Dantoft, Torben Jørgensen, Bodil Hammer Bech, Sanne Møller Thysen, Dorte Rytter","doi":"10.1007/s10654-025-01204-1","DOIUrl":"https://doi.org/10.1007/s10654-025-01204-1","url":null,"abstract":"<p>BiCoVac is a population-based Danish cohort aiming to examine whether Coronavirus disease 2019 (COVID-19) vaccines are associated with non-specific symptoms beyond the specific protection of COVID-19. Data were collected by four questionnaire surveys between May 2021 and July 2022 and the questionnaire distribution was aligned with the Danish COVID-19 vaccination program. All surveys collected self-reported information on symptoms (e.g., headache, nausea, and fatigue). The baseline survey additionally gathered information on lifestyle and health. Survey data were combined with data from the Danish registers including information on COVID-19 vaccination and COVID-19 test results. A total of 911,613 (25% of all Danish citizens aged 16 to 65) were randomly sampled for the cohort and 252,401 initiated the baseline questionnaire. Of these, 59% (<i>n</i> = 149,070) participated in the 1st follow-up, 43% (<i>n</i> = 107,655) in the 2nd follow-up, and 25% (<i>n</i> = 63,737) in the 3rd follow-up. Women and individuals above 40 years of age were more likely to participate. Among vaccinated respondents, 25–38% reported moderate to severe immediate symptoms following COVID-19 vaccination, varying by vaccine doses. Females, younger individuals, and those with prior COVID-19 reported more immediate symptoms. Results of potential non-specific symptoms following COVID-19 vaccination did not reveal higher risk of involuntary movements among vaccinated individuals compared to unvaccinated individuals. Currently (December 2024), we are further investigating the effects of COVID-19 vaccines on other non-specific symptoms and exploring whether specific characteristics render some individuals more susceptible to report non-specific symptoms. In addition, long-term symptoms following COVID-19 are being investigated.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"17 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of mortality tables by level of deprivation in the study of social inequalities in cancer survival","authors":"Sarah Wilson, Ophelie Merville, Olivier Dejardin, Josephine Gardy, Quentin Rollet, Valerie Jooste, Francim Network, Florence Molinie, Laure Tron, Guy Launoy","doi":"10.1007/s10654-024-01199-1","DOIUrl":"https://doi.org/10.1007/s10654-024-01199-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Previous studies have reported lower net survival probabilities for socioeconomically deprived patients, using non-deprivation specific lifetables. Not accounting for the social gradient in background mortality could potentially overestimate the effect of deprivation on net survival. The aim of this study was to estimate the impact of taking into account the social gradient of expected mortality in the general population on the study of the social gradient of survival of people with cancer.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>French cancer registry data was analyzed, with 190,902 incident cases of nineteen cancer sites between 2013 and 2015. Deprivation was measured using the European deprivation index (EDI). Net survival was estimated thanks to additive models with French lifetables stratified on deprivation level with the EDI, using the non-parametric Pohar-perme method and flexible excess hazard modelling with multidimensional penalized splines, firstly with non-specific lifetables then with the deprivation specific-lifetables.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A significant effect of EDI on excess mortality hazard (EMH) remained when using the deprivation-specific lifetables for colorectal, lung cancer and melanoma in both sexes, and esophagus, bladder, head and neck and liver cancer for men, and breast, cervix and uterine cancer for women. The only site where the effect of EDI on EMH was no longer significant when using deprivation-specific lifetables was prostate cancer.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The use of deprivation-specific lifetables confirms the existence of a social gradient in cancer survival, indicating that these inequalities do not result from inequalities in background mortality. Development of such deprivation-specific lifetables for future years is crucial to understand mechanisms of social inequalities and work towards reducing the social burden.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"26 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risks and rates, and the mathematical link between them","authors":"James A. Hanley","doi":"10.1007/s10654-024-01191-9","DOIUrl":"https://doi.org/10.1007/s10654-024-01191-9","url":null,"abstract":"<p>The risk over a given time span can be calculated as one minus the exponentiated value of the negative of the integral of the incidence density function (or hazard rate function) over that time span. This relationship is widely used but, in the few instances where textbooks have presented it, the derivations of it tend to be purely mathematical. I first review the historical contexts, definitions, distinctions and links. I then offer a more intuitive heuristic approach that draws on the conceptualization of a person-year in Edmonds’ 1832 definition of the force of mortality, and on the number of replacements in a dynamic population. Similarly I show how the Nelson-Aalen risk estimator can be seen in the context of this historical conceptualization of a person-year, scaled to the experience of a dynamic population of (constant) size 1.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"15 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cohort profile: the provincial opioid agonist treatment cohort in Ontario, Canada","authors":"Kristen A. Morin, Mark R. Tatangelo, Shreedhar Acharya, David C. Marsh","doi":"10.1007/s10654-025-01202-3","DOIUrl":"https://doi.org/10.1007/s10654-025-01202-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Opioid Agonist Treatment (OAT) is the most effective intervention for opioid use disorder (OUD), but retention has decreased due to increasingly potent drugs like fentanyl. This cohort can be used retrospectively to observe trends in service utilization, healthcare integration, healthcare costs and patient outcomes. It also facilitates the design of observational studies to mimic a prospective design.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study used linked administrative data from ICES to create a cohort of 137,035 individuals who received at least one prescription of methadone or buprenorphine/naloxone between 2014 and 2022. Data were linked using de-identified personal health numbers. Variables included age, sex, rurality, income, homelessness, and mental health conditions. Regional differences in OAT use, retention, and mortality were analyzed.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Of the cohort, 56.1% began OAT after 2014. Southern Ontario participants more often started on methadone (53.2%), while Northern Ontario patients favored buprenorphine/naloxone (62.7%). Northern patients were younger, more likely to be female, live in rural areas, and face homelessness. The death rate was higher in Southern Ontario (22.1%) than in Northern Ontario (13.2%). Retention declined over time, with 73.4% of patients remaining in treatment at the study's end.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The findings highlight regional disparities in OAT delivery and emphasize the need for region-specific strategies, particularly in rural areas, to improve retention and reduce mortality.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"20 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Global Burden of Diseases study-derived dietary scores with mortality and chronic disease risk: a comprehensive analysis from the prospective NutriNet-Santé study","authors":"Emmanuelle Kesse-Guyot, Julia Baudry, Justine Berlivet, Elie Perraud, Benjamin Allès, Chantal Julia, Léopold K. Fezeu, Serge Hercberg, François Mariotti, Mathilde Touvier, Hélène Fouillet","doi":"10.1007/s10654-024-01196-4","DOIUrl":"https://doi.org/10.1007/s10654-024-01196-4","url":null,"abstract":"<p>The Global Burden of Diseases (GBD) network has proposed theoretical minimum risk exposure level (TMREL) for leading risk factors associated with diet that minimize the risk of morbimortality from chronic diseases. TMREL can be applied to develop follow-up or evaluation indicators in individual studies. The validity of these scores can be tested by assessing associations with health outcomes in prospective cohorts. In this study conducted within the NutriNet-Santé cohort, four dietary scores (TMREL-Risk Score, TMREL-Probability of adequacy, TMREL-standardized distance, and TMREL dietary score) using different scoring methods were developed, with higher scores reflecting less healthy diets. Associations of these scores with the risk of type 2 diabetes, cancer, cardiovascular diseases (CVD) and mortality were estimated using multivariable Cox proportional hazards models, adjusted for a wide range of covariates. Counterfactual and marginal structural models were used to infer causality. Analyses were conducted in a sample of up to103,324 participants ((78.3% women, mean age of 43.6 years old (y) (SD = 14.6)), followed for a median of 8.47 (IQR = 14.7) years (2009–2024). The association with dietary scores (for 1SD-increase) varied in magnitude for each health outcome. For mortality, HR varied from 1.12 (95%CI = 1.07–1.18, ) to 1.18 (95%CI = 1.12–1.24) for TMREL-Stdis and TMREL-DI, for overall cancer from 1.07 (95%CI = 1.03–1.12) to 1.09 (1.04–1.13) for TMREL-RS and TMREL-PA, for CVD from 1.07 (95%CI = 1.00-1.16) to 1.12 (95%CI = 1.04–1.20) for TMREL-PA and TMREL-RS, and for type 2 diabetes from 1.33 (95%CI = 1.23–1.43) to 1.47 (95%CI = 1.36–1.59) for TMREL-DI and TMREL-PA. Marginal structural Cox models strengthened all associations compared to classical analyses. Standardized survival curves showed clear associations, especially for the risk of cancer and type 2 diabetes. Dietary scores based on GBD TMREL can serve as key indicators for characterizing diet quality in relation to long-term health, and using different scoring systems helped evaluate the robustness of these associations.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"9 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The associations of long-term physical activity in adulthood with later biological ageing and all-cause mortality – a prospective twin study","authors":"Anna Kankaanpää, Asko Tolvanen, Laura Joensuu, Katja Waller, Aino Heikkinen, Jaakko Kaprio, Miina Ollikainen, Elina Sillanpää","doi":"10.1007/s10654-024-01200-x","DOIUrl":"https://doi.org/10.1007/s10654-024-01200-x","url":null,"abstract":"<p>Objectives: The association between leisure-time physical activity (LTPA) and a lower risk of mortality is susceptible to bias from multiple sources. We investigated the potential of biological ageing to mediate the association between long-term LTPA and mortality and whether the methods used to account for reverse causality affect the interpretation of this association. Methods: Study participants were twins from the older Finnish Twin Cohort (<i>n</i> = 22,750; 18–50 years at baseline). LTPA was assessed using questionnaires in 1975, 1981 and 1990. The mortality follow-up lasted until 2020 and biological ageing was assessed using epigenetic clocks in a subsample (<i>n</i> = 1,153) with blood samples taken during the follow-up. Using latent profile analysis, we identified classes with distinct longitudinal LTPA patterns and studied differences in biological ageing between these classes. We employed survival models to examine differences in total, short-term and long-term all-cause mortality, and multilevel models for twin data to control for familial factors. Results: We identified four classes of long-term LTPA: sedentary, moderately active, active and highly active. Although biological ageing was accelerated in sedentary and highly active classes, after adjusting for other lifestyle-related factors, the associations mainly attenuated. Physically active classes had a maximum 7% lower risk of total mortality over the sedentary class, but this association was consistent only in the short term. After accounting for familial factors and excluding participants reporting prevalent cardiovascular diseases, LTPA exhibited less favourable associations with mortality. Conclusion: The association between LTPA and lower all-cause mortality may be largely due to genetic confounding and reverse causality.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"74 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between preconception and early pregnancy exposure to fine particulate matter and nervous system anomalies: a nested case-control study","authors":"Bao-Ru Chuang, Chung-Chin Lee, Yu-Ting Lin, Chau-Ren Jung, Mei-Ling Chen, Bing-Fang Hwang","doi":"10.1007/s10654-024-01198-2","DOIUrl":"https://doi.org/10.1007/s10654-024-01198-2","url":null,"abstract":"<p>Although several environmental factors may increase the risk of nervous system anomalies, the association between exposure to particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM_2.5) and nervous system anomalies is not completely understood. This study aimed to examine the association between expoure to PM_2.5 and nervous system anomalies, including specific phenotypes during preconception and early pregnancy and determine the crucial time windows. We conducted a nested case-control study from the Taiwan Maternal and Child Health Database between 2004 and 2017. We applied satellite-based models with a 1 km resolution to estimate the weekly average PM_2.5 from 13 weeks before conception to the first 8 weeks of pregnancy. We used conditional logistic regression with distributed lag nonlinear models (DLNMs) to assess the effects of weekly average PM_2.5 on the risk of nervous system anomalies and exposure-response relationships. We identified 12,383 incident nervous system anomalies cases in 2,571,300 participants. A 10 µg/m³ increase in PM_2.5 concentrations from a reference value of 25 µg/m³ was associated with higher risk of nervous system anomalies (adjusted odds ratio [aOR]: 1.21; 95% confidence incidence [CI]: 1.18, 1.25) and encephalocele (aOR: 1.56; 95% CI: 1.33, 1.84) from 13 weeks before conception to the first 8 weeks of gestation. Anencephaly showed a significant association with PM_2.5 exposure during the 13 weeks before conception (aOR: 1.48; 95% CI: 1.02, 2.51). In DLNMs, the risk of nervous system anomalies was elevated each week from 8 to 11 weeks before conception to 1–8 weeks of gestation. Our findings suggest that exposure to PM_2.5 during preconception and early pregnancy may increase the risk of nervous system anomalies in offspring, particularly neural tube defects such as anencephaly and encephalocele.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"40 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dutch Early-Stage Melanoma (D-ESMEL) study: a discovery set and validation cohort to predict the absolute risk of distant metastases in stage I/II cutaneous melanoma","authors":"Catherine Zhou, Antien L. Mooyaart, Thamila Kerkour, Marieke W. J. Louwman, Marlies Wakkee, Yunlei Li, Quirinus J. M. Voorham, Annette Bruggink, Tamar E. C. Nijsten, Loes M. Hollestein","doi":"10.1007/s10654-024-01188-4","DOIUrl":"https://doi.org/10.1007/s10654-024-01188-4","url":null,"abstract":"<p>Early-stage cutaneous melanoma patients generally have a favorable prognosis, yet a significant proportion of metastatic melanoma cases arise from this group, highlighting the need for improved risk stratification using novel prognostic biomarkers. The Dutch Early-Stage Melanoma (D-ESMEL) study introduces a robust, population-based methodology to develop an absolute risk prediction model for stage I/II melanoma, incorporating clinical, imaging, and multi-omics data to identify patients at increased risk for distant metastases. Utilizing the Netherlands Cancer Registry and Dutch Nationwide Pathology Databank, we collected primary tumor samples from early-stage melanoma patients, with and without distant metastases during follow-up. Our study design includes a discovery set of metastatic cases and matched controls to identify novel prognostic factors, followed by a validation cohort using a nested case–control design to validate these factors and to build a risk prediction model. Tissue sections underwent Hematoxylin &amp; Eosin (H&amp;E) staining, RNA sequencing (RNAseq), DNA sequencing (DNAseq), immunohistochemistry (IHC), and multiplex immunofluorescence (MxIF).The discovery set included 442 primary melanoma samples (221 case–control sets), with 46% stage I and 54% stage II melanomas. The median time to distant metastasis was 3.4 years, while controls had a median follow-up time of 9.8 years. The validation cohort included 154 cases and 154 controls from a random population-based selection of 5,815 patients. Our approach enabled the collection of a large number of early-stage melanoma samples from population-based databases with extensive follow-up and a sufficient number of metastatic events. This methodology in prognostic cancer research holds the potential to impact clinical decision-making through absolute risk prediction.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"25 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}