Pub Date : 2025-10-31DOI: 10.1007/s10654-025-01325-7
Tomoyuki Kawada
{"title":"Moderate alcohol drinking and incident dementia: a risk assessment","authors":"Tomoyuki Kawada","doi":"10.1007/s10654-025-01325-7","DOIUrl":"https://doi.org/10.1007/s10654-025-01325-7","url":null,"abstract":"","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"6 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145404267","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}
Tumors likely develop over years/decades, implying that assessing long-term exposure to risk factors is crucial in cancer epidemiology. An increasing trend of long-term risk factor exposures starting from early life since the mid-twentieth century appears to have contributed to the epidemics of early-onset cancer (EOC) worldwide. A rising incidence of EOC has been reported in various body sites such as the bone marrow, bile duct, breast, colorectum, esophagus, gallbladder, head and neck, kidney, liver, pancreas, stomach, and uterine corpus. To address an intractable gap between long-term exposure assessments and tumoral molecular/microenvironmental profiling in EOC research, here we describe a framework using the prospective cohort incident-tumor biobank method (PCIBM), which was recently conceptualized. The PCIBM enables prospective molecular pathological epidemiology research that can link long-term exposures with tumor pathogenic signatures. We illustrate this framework using the study of early-onset colorectal cancer (EOCRC). First, one recognizes overlaps of the characteristics of EOCRC and later-onset counterparts. Second, EOCRC tumoral, multi-omic, or microenvironmental features are discovered and replicated. Third, using the PCIBM, long-term exposure variables are examined in relation to the incidence of all-age colorectal cancer subtypes possessing EOCRC tumoral features. Fourth, identified putative risk factors are tested for EOCRC incidence. This framework, which has provided etiological insights and advanced our understanding of EOCRC pathogenesis, is widely applicable to EOC in various organs. In addition, this research modality with artificial intelligence-driven computational tools should be used in lifecourse and other prospective cohort studies to improve our knowledge of EOC pathogenesis.
{"title":"The early-onset cancer epidemics: evidence synthesis using the prospective cohort incident-tumor biobank method.","authors":"Shuji Ogino,Satoko Ugai,Tsuyoshi Hamada,Tomotaka Ugai","doi":"10.1007/s10654-025-01322-w","DOIUrl":"https://doi.org/10.1007/s10654-025-01322-w","url":null,"abstract":"Tumors likely develop over years/decades, implying that assessing long-term exposure to risk factors is crucial in cancer epidemiology. An increasing trend of long-term risk factor exposures starting from early life since the mid-twentieth century appears to have contributed to the epidemics of early-onset cancer (EOC) worldwide. A rising incidence of EOC has been reported in various body sites such as the bone marrow, bile duct, breast, colorectum, esophagus, gallbladder, head and neck, kidney, liver, pancreas, stomach, and uterine corpus. To address an intractable gap between long-term exposure assessments and tumoral molecular/microenvironmental profiling in EOC research, here we describe a framework using the prospective cohort incident-tumor biobank method (PCIBM), which was recently conceptualized. The PCIBM enables prospective molecular pathological epidemiology research that can link long-term exposures with tumor pathogenic signatures. We illustrate this framework using the study of early-onset colorectal cancer (EOCRC). First, one recognizes overlaps of the characteristics of EOCRC and later-onset counterparts. Second, EOCRC tumoral, multi-omic, or microenvironmental features are discovered and replicated. Third, using the PCIBM, long-term exposure variables are examined in relation to the incidence of all-age colorectal cancer subtypes possessing EOCRC tumoral features. Fourth, identified putative risk factors are tested for EOCRC incidence. This framework, which has provided etiological insights and advanced our understanding of EOCRC pathogenesis, is widely applicable to EOC in various organs. In addition, this research modality with artificial intelligence-driven computational tools should be used in lifecourse and other prospective cohort studies to improve our knowledge of EOC pathogenesis.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"59 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373698","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}
Pub Date : 2025-10-27DOI: 10.1007/s10654-025-01318-6
Michelle M Dunk,Huijie Huang,Jiao Wang,Abigail Dove,Sakura Sakakibara,Jie Guo,Adrián Carballo-Casla,David A Bennett,Weili Xu
Pro-inflammatory diets are associated with cognitive decline and dementia, but their impact on brain aging is unclear. We investigated the association between a pro-inflammatory diet and brain age, taking into account age, genetic risk for dementia, and systemic inflammation. UK Biobank participants (N = 21,473) aged 40-70 years and free of neurological disorders were included. The Dietary Inflammatory Index (DII) was calculated from participants' average intake of 31 nutrients, assessed up to five times via 24-h recalls. Participants were categorized into four DII groups (group 1, anti-inflammatory, DII < -2; group 2, DII -2 to < 0; group 3, DII 0 to < 2; group 4, DII ≥ 2), with group 4 reflecting the most pro-inflammatory diet. Brain age was estimated using a machine learning model based on 1079 structural and functional MRI measures, obtained approximately 9 years after baseline. We calculated brain age gap (BAG; brain age minus chronological age), where BAG > 0 reflects a biologically older brain than chronological age. An Alzheimer's disease polygenic risk score (PRSAD), APOE4 status, and a composite score of systemic inflammation (INFLA-score) were determined from baseline blood samples. More pro-inflammatory diets were associated with increasingly greater BAG, with advanced brain age by [Formula: see text]=0.50 [95% CI 0.20, 0.80] years among those in group 4. There were no interactions between DII and age, PRSAD, or APOE4 in relation to BAG, but associations were stronger among adults ≥ 60 years. INFLA-score mediated 8% of the DII-BAG association. These findings suggest that a pro-inflammatory diet may accelerate brain aging, especially in older adults.
促炎饮食与认知能力下降和痴呆有关，但它们对大脑衰老的影响尚不清楚。考虑到年龄、痴呆的遗传风险和全身性炎症，我们调查了促炎饮食与脑年龄之间的关系。纳入英国生物银行参与者（N = 21,473），年龄40-70岁，无神经系统疾病。饮食炎症指数（DII）根据参与者的31种营养素的平均摄入量计算，通过24小时回忆评估多达5次。参与者被分为四个DII组(1组，抗炎组，DII < -2组；2组，DII -2至0反映了生理上比实际年龄大的大脑。从基线血液样本中确定阿尔茨海默病多基因风险评分（PRSAD）、APOE4状态和全身炎症综合评分（infla评分）。在第4组中，更多的促炎饮食与越来越大的BAG相关，与脑年龄的延长相关[公式：见原文]=0.50 [95% CI 0.20, 0.80]年。DII与年龄、PRSAD或与BAG相关的APOE4之间没有相互作用，但在≥60岁的成年人中相关性更强。infla评分介导了8%的DII-BAG关联。这些发现表明，促炎饮食可能会加速大脑衰老，尤其是在老年人中。
{"title":"The association between a pro-inflammatory diet and brain age in middle-aged and older adults.","authors":"Michelle M Dunk,Huijie Huang,Jiao Wang,Abigail Dove,Sakura Sakakibara,Jie Guo,Adrián Carballo-Casla,David A Bennett,Weili Xu","doi":"10.1007/s10654-025-01318-6","DOIUrl":"https://doi.org/10.1007/s10654-025-01318-6","url":null,"abstract":"Pro-inflammatory diets are associated with cognitive decline and dementia, but their impact on brain aging is unclear. We investigated the association between a pro-inflammatory diet and brain age, taking into account age, genetic risk for dementia, and systemic inflammation. UK Biobank participants (N = 21,473) aged 40-70 years and free of neurological disorders were included. The Dietary Inflammatory Index (DII) was calculated from participants' average intake of 31 nutrients, assessed up to five times via 24-h recalls. Participants were categorized into four DII groups (group 1, anti-inflammatory, DII < -2; group 2, DII -2 to < 0; group 3, DII 0 to < 2; group 4, DII ≥ 2), with group 4 reflecting the most pro-inflammatory diet. Brain age was estimated using a machine learning model based on 1079 structural and functional MRI measures, obtained approximately 9 years after baseline. We calculated brain age gap (BAG; brain age minus chronological age), where BAG > 0 reflects a biologically older brain than chronological age. An Alzheimer's disease polygenic risk score (PRSAD), APOE4 status, and a composite score of systemic inflammation (INFLA-score) were determined from baseline blood samples. More pro-inflammatory diets were associated with increasingly greater BAG, with advanced brain age by [Formula: see text]=0.50 [95% CI 0.20, 0.80] years among those in group 4. There were no interactions between DII and age, PRSAD, or APOE4 in relation to BAG, but associations were stronger among adults ≥ 60 years. INFLA-score mediated 8% of the DII-BAG association. These findings suggest that a pro-inflammatory diet may accelerate brain aging, especially in older adults.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"106 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373700","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}
Pub Date : 2025-10-27DOI: 10.1007/s10654-025-01321-x
Olof M Östergren,Emilie Counil,Arizo Karimi,Tove Fall,Jonas Björk,Karl Gauffin
In the early stages of the COVID-19 pandemic, PCR testing served different purposes for individuals and for policy makers. Policy makers relied on testing for representative case numbers to track and mitigate the spread of the disease whereas individuals needed tests to protect themselves and others, or to travel or go work. Systematic differences in testing across population groups can bias case numbers, making it more difficult for policy makers to implement effective non-pharmaceutical interventions. We link records of 494 699 PCR-tests taken between 2020-07-01 and 2020-12-31 to individual records in several administrative registers for 1 480 126 working age individuals in the counties of Stockholm and Scania in Sweden. We estimate the likelihood of getting tested, test positivity rate and hospitalization risk by sex, household size, migration background, education, income and medical risk factors in the individual or in the household using regression models with age, occupation and neighbourhood as fixed effects. We find that testing behaviour vary independently by several demographic, socioeconomic and medical factors. Several groups that were at an elevated risk of being hospitalized for COVID-19, including men, individuals born outside Europe and those with low education, had low testing rates and high positivity rates. Numbers of confirmed SARS-CoV-2 infections reflect both infection rates and the testing behaviour of the population. To improve the utility of testing in future pandemics, policy makers may collect data on negative tests and dedicate part of the testing capacity for representative screening.
{"title":"Who got tested and who got sick? Sociodemographic inequalities in COVID-19 testing and hospitalization among 1.48 million individuals in Sweden.","authors":"Olof M Östergren,Emilie Counil,Arizo Karimi,Tove Fall,Jonas Björk,Karl Gauffin","doi":"10.1007/s10654-025-01321-x","DOIUrl":"https://doi.org/10.1007/s10654-025-01321-x","url":null,"abstract":"In the early stages of the COVID-19 pandemic, PCR testing served different purposes for individuals and for policy makers. Policy makers relied on testing for representative case numbers to track and mitigate the spread of the disease whereas individuals needed tests to protect themselves and others, or to travel or go work. Systematic differences in testing across population groups can bias case numbers, making it more difficult for policy makers to implement effective non-pharmaceutical interventions. We link records of 494 699 PCR-tests taken between 2020-07-01 and 2020-12-31 to individual records in several administrative registers for 1 480 126 working age individuals in the counties of Stockholm and Scania in Sweden. We estimate the likelihood of getting tested, test positivity rate and hospitalization risk by sex, household size, migration background, education, income and medical risk factors in the individual or in the household using regression models with age, occupation and neighbourhood as fixed effects. We find that testing behaviour vary independently by several demographic, socioeconomic and medical factors. Several groups that were at an elevated risk of being hospitalized for COVID-19, including men, individuals born outside Europe and those with low education, had low testing rates and high positivity rates. Numbers of confirmed SARS-CoV-2 infections reflect both infection rates and the testing behaviour of the population. To improve the utility of testing in future pandemics, policy makers may collect data on negative tests and dedicate part of the testing capacity for representative screening.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"11 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373699","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}
Pub Date : 2025-10-25DOI: 10.1007/s10654-025-01308-8
Magnus Kaijser,Maria Feychting,Stefan Skare,Fang Fang
PURPOSETo assess the validity of information on the date of diagnosis of intracranial tumors in the Swedish National Cancer Register.MATERIALS AND METHODSThe study was conducted in Region Stockholm, covering approximately 2.4 million inhabitants. Data from the Image and Function Service (BFT) archive, which contains a population-based database of all diagnostic radiology in the Stockholm Region, was used. The study included all primary cases of intracranial tumors (ICD10 codes C70 and C71) reported from Stockholm to the National Cancer Register from 2010 to 2020. Radiology reports from CT and MRI exams performed from 2000 to 2020 were reviewed. Reports from exams conducted more than one month before the Swedish Cancer Register diagnosis were manually examined to validate the date of diagnosis.RESULTSFor 98.8% of the brain tumor patients and 96.2% of the meningioma patients, the date of first radiological diagnosis was one month or less prior to date of diagnosis in the Swedish Cancer Register. Of the patients with radiological diagnoses more than one month prior to cancer register diagnosis, 30 patients (1.0%) had tumors reported to the register one month to one year after radiological diagnosis, and 36 patients (1.2%) had tumors reported more than one year later.CONCLUSIONThe study found that for patients from the Stockholm Region with intracranial tumors reported to the Swedish Cancer Register during the period 2010 through 2020, date of diagnosis is highly accurate.
{"title":"The validity of the information on date of diagnosis of intracranial tumors in the Swedish cancer register.","authors":"Magnus Kaijser,Maria Feychting,Stefan Skare,Fang Fang","doi":"10.1007/s10654-025-01308-8","DOIUrl":"https://doi.org/10.1007/s10654-025-01308-8","url":null,"abstract":"PURPOSETo assess the validity of information on the date of diagnosis of intracranial tumors in the Swedish National Cancer Register.MATERIALS AND METHODSThe study was conducted in Region Stockholm, covering approximately 2.4 million inhabitants. Data from the Image and Function Service (BFT) archive, which contains a population-based database of all diagnostic radiology in the Stockholm Region, was used. The study included all primary cases of intracranial tumors (ICD10 codes C70 and C71) reported from Stockholm to the National Cancer Register from 2010 to 2020. Radiology reports from CT and MRI exams performed from 2000 to 2020 were reviewed. Reports from exams conducted more than one month before the Swedish Cancer Register diagnosis were manually examined to validate the date of diagnosis.RESULTSFor 98.8% of the brain tumor patients and 96.2% of the meningioma patients, the date of first radiological diagnosis was one month or less prior to date of diagnosis in the Swedish Cancer Register. Of the patients with radiological diagnoses more than one month prior to cancer register diagnosis, 30 patients (1.0%) had tumors reported to the register one month to one year after radiological diagnosis, and 36 patients (1.2%) had tumors reported more than one year later.CONCLUSIONThe study found that for patients from the Stockholm Region with intracranial tumors reported to the Swedish Cancer Register during the period 2010 through 2020, date of diagnosis is highly accurate.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"106 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357851","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}
Since 2019, death data published by the Institute of Statistics and Economic Studies (INSEE) are available, raising questions regarding methodology and potential biases in overall survival analyses. We conducted a simulation study to quantify biases and formulate recommendations for using these data for research. We compared several approaches for estimating overall survival by (i) including only hospital data (EMR), (ii) adding deaths known to the INSEE (EMR_INSEE), or (iii) considering patients without reported death as "alive" (EMR_INSEE_IMP). We conducted simulation studies by varying the mortality risk of the disease studied, rate of loss to follow-up, and death capture rate from INSEE. With the EMR_INSEE approach, the risk of bias appeared to be significant in all clinical scenarios, with a large underestimation of overall survival. On comparing two survival curves, the hazard ratio estimate was highly biased, and type-I and II errors were inflated. With the EMR_INSEE_IMP approach, the risk of bias seemed low and acceptable for clinical situations involving low mortality, especially if loss to follow-up was low. However, some clinical situations seemed to require greater vigilance because of risk of bias when mortality was intermediate or high, especially when the risk of loss to follow-up was high. To our knowledge, this is the first study to assess the impact of using INSEE data in addition to hospital data on vital status. Various simulated scenarios enabled us to quantify the biases involved and thus make recommendations on the various possible strategies for using these data.
{"title":"Estimating overall survival by combining administrative and hospital death data: a methodological challenge.","authors":"Pierre-Yves Cren,Clémence Leguillette,Franck Craynest,Ali Hammoudi,Maël Barthoulot,Matthieu Carton,Thomas Filleron,Sylvie Chabaud,Youenn Drouet,Marie-Cécile Le Deley","doi":"10.1007/s10654-025-01278-x","DOIUrl":"https://doi.org/10.1007/s10654-025-01278-x","url":null,"abstract":"Since 2019, death data published by the Institute of Statistics and Economic Studies (INSEE) are available, raising questions regarding methodology and potential biases in overall survival analyses. We conducted a simulation study to quantify biases and formulate recommendations for using these data for research. We compared several approaches for estimating overall survival by (i) including only hospital data (EMR), (ii) adding deaths known to the INSEE (EMR_INSEE), or (iii) considering patients without reported death as \"alive\" (EMR_INSEE_IMP). We conducted simulation studies by varying the mortality risk of the disease studied, rate of loss to follow-up, and death capture rate from INSEE. With the EMR_INSEE approach, the risk of bias appeared to be significant in all clinical scenarios, with a large underestimation of overall survival. On comparing two survival curves, the hazard ratio estimate was highly biased, and type-I and II errors were inflated. With the EMR_INSEE_IMP approach, the risk of bias seemed low and acceptable for clinical situations involving low mortality, especially if loss to follow-up was low. However, some clinical situations seemed to require greater vigilance because of risk of bias when mortality was intermediate or high, especially when the risk of loss to follow-up was high. To our knowledge, this is the first study to assess the impact of using INSEE data in addition to hospital data on vital status. Various simulated scenarios enabled us to quantify the biases involved and thus make recommendations on the various possible strategies for using these data.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"2 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331809","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}
Pub Date : 2025-10-14DOI: 10.1007/s10654-025-01313-x
Yu Du,Zi-Jian Kang,Qiang Tong,Han-Lei Jiang,Ran Cui,Shiow-Ing Wang,James Cheng-Chung Wei,Sheng-Ming Dai
The co-occurrence of Hashimoto's thyroiditis (HT) and Sjogren's syndrome (SS), two seemingly unrelated diseases that both affect huge amounts of people worldwide, has been indicated previously in several case reports. However, there is a lack of higher-level evidences proving their comorbidity, and the underlying mechanisms remain unelucidated. This in-depth study aims to provide evidences for the comorbidity between HT and SS and explore the genetic and immunological mechanisms that may underlie their occurrence. Leveraging large retrospective cohorts from the collaborative electronic health record database, matched by propensity scores, we evaluated the risk of developing SS in 190,653 patients with HT and the risk of developing HT in 73,306 patients with SS. A Mendelian randomization (MR) approach was applied to investigate the causal relationship between the two conditions. Transcriptomic analysis of GEO datasets further explored common immunological markers. Our large-scale propensity score-matched analysis revealed a significantly higher risk of SS in HT patients compared to controls, with a hazard ratio (HR) of 3.227 and a confidence interval (CI) of 2.987-3.486, over a 20-year follow-up period. Similarly, a reciprocal risk was observed, with SS patients at a higher risk of developing HT (HR, 2.780; CI, 2.568-3.009) compared to controls. In Mendelian randomization study, random-effects IVW method showed a potential causal effect of HT on SS (IVW OR = 1.871, 95% CI = 1.265-2.768; P = 0.002). Furthermore, transcriptomic analysis showed there were 127 common up-regulated differential expressed genes (DEGs) between HT and SS, accounting for 29.4% of upregulated DEGs in HT and 14.5% of upregulated DEGs. Common hub genes in HT and SS were also determined, including CD4, IFNG, CCR7, and ITGAM, suggesting a shared immunopathogenesis and highlighting potential therapeutic targets. Our findings revealed a strong correlation between HT and SS, supported by evidences from clinical cohorts, the genetical causal effect, and shared immunopathogenesis, offering new insights into the cooccurrence of the two diseases.
桥本甲状腺炎（HT）和干燥综合征（SS）这两种看似不相关的疾病在世界范围内都影响着大量的人，在以前的一些病例报告中已经指出了这两种疾病的共同发生。然而，缺乏更高水平的证据证明它们的共病性，潜在的机制仍然不清楚。本研究旨在为HT和SS的共病提供证据，并探讨其发生的遗传和免疫学机制。利用来自协作电子健康记录数据库的大型回顾性队列，通过倾向评分进行匹配，我们评估了190,653名HT患者发生SS的风险和73,306名SS患者发生HT的风险。采用孟德尔随机化（MR）方法研究了两种情况之间的因果关系。GEO数据集的转录组学分析进一步探索了常见的免疫标志物。我们的大规模倾向评分匹配分析显示，在20年的随访期间，HT患者发生SS的风险明显高于对照组，风险比（HR）为3.227，置信区间（CI）为2.987-3.486。同样，观察到相互风险，与对照组相比，SS患者发生HT的风险更高（HR, 2.780； CI, 2.568-3.009）。在孟德尔随机化研究中，随机效应IVW方法显示HT对SS有潜在的因果影响（IVW OR = 1.871, 95% CI = 1.265 ~ 2.768; P = 0.002）。此外，转录组学分析显示，HT和SS共有127个差异表达基因（deg）上调，分别占HT中上调deg的29.4%和上调deg的14.5%。HT和SS的共同枢纽基因包括CD4、IFNG、CCR7和ITGAM，这表明它们具有共同的免疫发病机制，并突出了潜在的治疗靶点。我们的研究结果揭示了HT和SS之间的强相关性，得到了临床队列证据、遗传因果效应和共同的免疫发病机制的支持，为两种疾病的共发提供了新的见解。
{"title":"An in-depth study of the correlation between Hashimoto's thyroiditis and Sjogren's syndrome: multiple evidences from large cohorts, Mendelian randomization, and transcriptomic analysis.","authors":"Yu Du,Zi-Jian Kang,Qiang Tong,Han-Lei Jiang,Ran Cui,Shiow-Ing Wang,James Cheng-Chung Wei,Sheng-Ming Dai","doi":"10.1007/s10654-025-01313-x","DOIUrl":"https://doi.org/10.1007/s10654-025-01313-x","url":null,"abstract":"The co-occurrence of Hashimoto's thyroiditis (HT) and Sjogren's syndrome (SS), two seemingly unrelated diseases that both affect huge amounts of people worldwide, has been indicated previously in several case reports. However, there is a lack of higher-level evidences proving their comorbidity, and the underlying mechanisms remain unelucidated. This in-depth study aims to provide evidences for the comorbidity between HT and SS and explore the genetic and immunological mechanisms that may underlie their occurrence. Leveraging large retrospective cohorts from the collaborative electronic health record database, matched by propensity scores, we evaluated the risk of developing SS in 190,653 patients with HT and the risk of developing HT in 73,306 patients with SS. A Mendelian randomization (MR) approach was applied to investigate the causal relationship between the two conditions. Transcriptomic analysis of GEO datasets further explored common immunological markers. Our large-scale propensity score-matched analysis revealed a significantly higher risk of SS in HT patients compared to controls, with a hazard ratio (HR) of 3.227 and a confidence interval (CI) of 2.987-3.486, over a 20-year follow-up period. Similarly, a reciprocal risk was observed, with SS patients at a higher risk of developing HT (HR, 2.780; CI, 2.568-3.009) compared to controls. In Mendelian randomization study, random-effects IVW method showed a potential causal effect of HT on SS (IVW OR = 1.871, 95% CI = 1.265-2.768; P = 0.002). Furthermore, transcriptomic analysis showed there were 127 common up-regulated differential expressed genes (DEGs) between HT and SS, accounting for 29.4% of upregulated DEGs in HT and 14.5% of upregulated DEGs. Common hub genes in HT and SS were also determined, including CD4, IFNG, CCR7, and ITGAM, suggesting a shared immunopathogenesis and highlighting potential therapeutic targets. Our findings revealed a strong correlation between HT and SS, supported by evidences from clinical cohorts, the genetical causal effect, and shared immunopathogenesis, offering new insights into the cooccurrence of the two diseases.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"28 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283952","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}
Severe chronic disease (SCD) in childhood may hinder not only physical health but also academic performance. In this population-based cohort study, we investigated educational outcomes among 20,979 Danish children with SCD (54.7% male) and 423,814 without SCD (51.1% male). We assessed completion of lower secondary school and grade point averages (GPAs). Completion and GPAs with 95% confidence intervals (95% CI) were estimated using logistic and linear regression models adjusted for sex, country of origin, and maternal education. Children with SCD had lower probability of completing 9th grade (male: 0.53 [95% CI 0.52-0.54], female: 0.63 [0.62-0.64]) than their peers without SCD (male: 0.70 [0.70-0.70], female: 0.82 [0.81-0.82]). Similarly, GPA was lower for children with SCD (male: 6.61 [6.55-6.66], female: 7.51 [7.45-7.56]) compared to those without (male: 6.86 [6.85-6.87], female: 7.90 [7.89-7.91]). The sex disparity persisted across all groups. Children of mothers with lower education experienced larger performance gaps. Neurological and perinatal conditions showed the poorest outcomes. Our findings demonstrate persistent educational inequalities among children with SCD, even in settings with universal healthcare and education, underscoring the need for targeted, cross-sectoral support.
儿童时期严重的慢性疾病（SCD）不仅会影响身体健康，还会影响学习成绩。在这项基于人群的队列研究中，我们调查了20,979名丹麦SCD儿童（54.7%为男性）和423,814名非SCD儿童（51.1%为男性）的教育结果。我们评估了初中学业完成情况和平均绩点（gpa）。使用经性别、原籍国和母亲教育程度调整的逻辑回归和线性回归模型估计毕业率和gpa的95%置信区间（95% CI）。SCD患儿完成9年级学业的概率（男性：0.53 [95% CI 0.52-0.54]，女性：0.63[0.62-0.64]）低于无SCD患儿（男性：0.70[0.70-0.70]，女性：0.82[0.81-0.82]）。同样，患有SCD的儿童的GPA（男性：6.61[6.55-6.66]，女性：7.51[7.45-7.56]）低于没有SCD的儿童（男性：6.86[6.85-6.87]，女性：7.90[7.89-7.91]）。性别差异在所有群体中都存在。母亲受教育程度较低的孩子表现差距更大。神经系统和围产期状况显示最差的结果。我们的研究结果表明，即使在全民医疗和教育的环境中，SCD儿童仍然存在教育不平等，这强调了有针对性的跨部门支持的必要性。
{"title":"Association between chronic diseases in childhood and subsequent educational achievement: a Danish register-based cohort study.","authors":"Ann-Sophie Buchardt,Andreas Jensen,Helene Kildegaard,Lone Graff Stensballe","doi":"10.1007/s10654-025-01315-9","DOIUrl":"https://doi.org/10.1007/s10654-025-01315-9","url":null,"abstract":"Severe chronic disease (SCD) in childhood may hinder not only physical health but also academic performance. In this population-based cohort study, we investigated educational outcomes among 20,979 Danish children with SCD (54.7% male) and 423,814 without SCD (51.1% male). We assessed completion of lower secondary school and grade point averages (GPAs). Completion and GPAs with 95% confidence intervals (95% CI) were estimated using logistic and linear regression models adjusted for sex, country of origin, and maternal education. Children with SCD had lower probability of completing 9th grade (male: 0.53 [95% CI 0.52-0.54], female: 0.63 [0.62-0.64]) than their peers without SCD (male: 0.70 [0.70-0.70], female: 0.82 [0.81-0.82]). Similarly, GPA was lower for children with SCD (male: 6.61 [6.55-6.66], female: 7.51 [7.45-7.56]) compared to those without (male: 6.86 [6.85-6.87], female: 7.90 [7.89-7.91]). The sex disparity persisted across all groups. Children of mothers with lower education experienced larger performance gaps. Neurological and perinatal conditions showed the poorest outcomes. Our findings demonstrate persistent educational inequalities among children with SCD, even in settings with universal healthcare and education, underscoring the need for targeted, cross-sectoral support.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"1 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283951","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}
Pub Date : 2025-10-10DOI: 10.1007/s10654-025-01316-8
Eric Fombonne
The Secretary of the US Department of Health & Human Services (HHSS) recently claimed that US estimates of the prevalence of autism confirmed the existence of an autism epidemic. Furthermore, HHSS asserted that the autism epidemic was driven by an environmental toxin which he promised to find in the following months. These claims are contradicted by studies showing that progress in the understanding, detection, diagnosis and management of autism have fueled the increasing prevalence. HHSS statements are also in sharp contrast with the opinion of scientists who have monitored the upward trend in autism prevalence in the US and worldwide. In this Commentary, we address sequentially each misconception and misinterpretation proffered by HHSS. We show that changes in the definition of autism, in diagnostic criteria and practices, in case ascertainment in surveys, the inclusion of less severe forms of autism and other contextual factors such as improved awareness, de-stigmatization, advocacy, improved access to service and better insurance coverage have all converged in increasing the prevalence of autism and that presenting the rise on autism prevalence as an epidemic is misleading. Furthermore, given the strong heritability of autism, its genetic and phenotypic heterogeneity and the paucity of leads on environmental risk, the promise to find an environmental toxin causally related to autism in upcoming months appears at best preposterous. We warn about the return of false theories and already debunked hypotheses on the etiology of autism when empirical data are ignored, scientific methodology is dismissed and experts' opinions disdained.
{"title":"The autism 'epidemic': misinterpretation, misinformation and conspiracy.","authors":"Eric Fombonne","doi":"10.1007/s10654-025-01316-8","DOIUrl":"https://doi.org/10.1007/s10654-025-01316-8","url":null,"abstract":"The Secretary of the US Department of Health & Human Services (HHSS) recently claimed that US estimates of the prevalence of autism confirmed the existence of an autism epidemic. Furthermore, HHSS asserted that the autism epidemic was driven by an environmental toxin which he promised to find in the following months. These claims are contradicted by studies showing that progress in the understanding, detection, diagnosis and management of autism have fueled the increasing prevalence. HHSS statements are also in sharp contrast with the opinion of scientists who have monitored the upward trend in autism prevalence in the US and worldwide. In this Commentary, we address sequentially each misconception and misinterpretation proffered by HHSS. We show that changes in the definition of autism, in diagnostic criteria and practices, in case ascertainment in surveys, the inclusion of less severe forms of autism and other contextual factors such as improved awareness, de-stigmatization, advocacy, improved access to service and better insurance coverage have all converged in increasing the prevalence of autism and that presenting the rise on autism prevalence as an epidemic is misleading. Furthermore, given the strong heritability of autism, its genetic and phenotypic heterogeneity and the paucity of leads on environmental risk, the promise to find an environmental toxin causally related to autism in upcoming months appears at best preposterous. We warn about the return of false theories and already debunked hypotheses on the etiology of autism when empirical data are ignored, scientific methodology is dismissed and experts' opinions disdained.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"2 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261520","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}
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