Pub Date : 2026-01-28DOI: 10.1007/s10654-026-01365-7
Paolo Boffetta,Giulia Collatuzzo,K M Venkat Narayan
The association between diabetes and low-level arsenic exposure in drinking water has not been adequately investigated. We conducted a two-stage meta-analysis of dose-response relationships from studies reporting incidence or prevalence of diabetes with average exposure up to 150 µg/L arsenic in drinking water. We conducted a literature search and included cross-sectional, case control and cohort studies and we extracted results for exposure to arsenic up to average concentration of 150 µg/L water. Prevalence and incidence were generically referred to as risk. We conducted study-specific linear regression to estimate the relative risk (RR) of diabetes for a 10 µg/L increase of arsenic, and combined the study-specific results in a random-effect meta-analysis. We addressed publication bias by excluding studies with the largest standard error; and identified a subset of high-quality studies. We also performed a one-stage meta-regression. We selected 11 studies including 12 populations from seven countries. The meta-analysis of their results yielded a relative risk (RR) of type 2 diabetes for a 10 µg/L arsenic increase within the range 0-150 µg/L equal to 1.07 (95% confidence interval [CI] 1.02-1.21, p heterogeneity = 0.006). There was evidence of publication bias (p = 0.004); after accounting for publication bias, the summary RR was 1.02 (95% CI 0.99-1.06, eight studies). The RR based on the high-quality studies was 1.03 (95% CI 0.97-1.09, five studies). The corresponding RR of the meta-regression was 1.007 (95% CI 0.998-1.017, 32 risk estimates). Accounting for publication bias and study quality, and considering heterogeneity of risk estimates, our two-stage meta-analysis supports a null association between low levels of arsenic in drinking water and type 2 diabetes.
糖尿病与饮用水中低水平砷暴露之间的关系尚未得到充分调查。我们进行了一项两阶段的荟萃分析，分析了饮用水中砷平均暴露量高达150微克/升时糖尿病发病率或患病率的剂量-反应关系。我们进行了文献检索，包括横断面研究、病例对照研究和队列研究，并提取了砷暴露于平均浓度为150 μ g/L水的结果。患病率和发病率通常被称为风险。我们进行了特定研究的线性回归，以估计砷含量每增加10微克/升，糖尿病的相对风险（RR），并将特定研究的结果结合在随机效应荟萃分析中。我们通过排除标准误差最大的研究来解决发表偏倚问题；并确定了一些高质量的研究。我们还进行了单阶段元回归。我们选择了11项研究，包括来自7个国家的12个人群。荟萃分析结果显示，在0 ~ 150µg/L范围内，砷浓度每增加10µg/L， 2型糖尿病的相对危险度（RR）为1.07（95%置信区间[CI] 1.02 ~ 1.21， p异质性= 0.006）。有证据表明存在发表偏倚（p = 0.004）；考虑发表偏倚后，总RR为1.02 （95% CI 0.99-1.06, 8项研究）。基于高质量研究的RR为1.03 （95% CI 0.97-1.09, 5项研究）。meta回归的相应RR为1.007 （95% CI 0.998-1.017, 32个风险估计）。考虑到发表偏倚和研究质量，并考虑到风险估计的异质性，我们的两阶段荟萃分析支持饮用水中低水平砷与2型糖尿病之间的零关联。
{"title":"Low-level exposure to arsenic in drinking water and risk of type 2 diabetes: a systematic review and meta-analysis.","authors":"Paolo Boffetta,Giulia Collatuzzo,K M Venkat Narayan","doi":"10.1007/s10654-026-01365-7","DOIUrl":"https://doi.org/10.1007/s10654-026-01365-7","url":null,"abstract":"The association between diabetes and low-level arsenic exposure in drinking water has not been adequately investigated. We conducted a two-stage meta-analysis of dose-response relationships from studies reporting incidence or prevalence of diabetes with average exposure up to 150 µg/L arsenic in drinking water. We conducted a literature search and included cross-sectional, case control and cohort studies and we extracted results for exposure to arsenic up to average concentration of 150 µg/L water. Prevalence and incidence were generically referred to as risk. We conducted study-specific linear regression to estimate the relative risk (RR) of diabetes for a 10 µg/L increase of arsenic, and combined the study-specific results in a random-effect meta-analysis. We addressed publication bias by excluding studies with the largest standard error; and identified a subset of high-quality studies. We also performed a one-stage meta-regression. We selected 11 studies including 12 populations from seven countries. The meta-analysis of their results yielded a relative risk (RR) of type 2 diabetes for a 10 µg/L arsenic increase within the range 0-150 µg/L equal to 1.07 (95% confidence interval [CI] 1.02-1.21, p heterogeneity = 0.006). There was evidence of publication bias (p = 0.004); after accounting for publication bias, the summary RR was 1.02 (95% CI 0.99-1.06, eight studies). The RR based on the high-quality studies was 1.03 (95% CI 0.97-1.09, five studies). The corresponding RR of the meta-regression was 1.007 (95% CI 0.998-1.017, 32 risk estimates). Accounting for publication bias and study quality, and considering heterogeneity of risk estimates, our two-stage meta-analysis supports a null association between low levels of arsenic in drinking water and type 2 diabetes.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"78 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056881","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 : 2026-01-28DOI: 10.1007/s10654-026-01367-5
Cassandra Freitas,James A Hanley
During the COVID-19 pandemic, vaccine development took center stage in the media and minds of the global community. This same daily scrutiny was also applied to the first public registered vaccine trial of anthrax prevention among livestock led by French scientist Louis Pasteur in 1881. At a meeting with the president of the Agricultural Society of Melun, Pasteur outlined what might be considered the first "registered" vaccine trial protocol. The trial proposed a three-arm trial where anthrax-naïve sheep (n = 60) and cows (n = 10) would be assigned either to a treatment group consisting of a 2-dose anthrax vaccination in addition to an anthrax challenge, a control group consisting of an unvaccinated group given the anthrax challenge or a second control group which received neither vaccine nor anthrax challenge. All vaccinated sheep and cows were alive 48 h post-challenge. All unvaccinated sheep who received the anthrax challenge died within 48 h post-challenge, and the unvaccinated cows developed large edemas at the site of inoculation. Witnessing the 100% efficacy of Pasteur's vaccine were hundreds of, mostly skeptical, onlookers including journalists who disseminated the big news across Europe within days. Two months later, the results of the trial reached North America, via attendees who had heard Pasteur's address at the International Medical Congress in London in August 1881. Pasteur's anthrax vaccine trial laid the foundations for the systematic, public, and a priori reporting of clinical trial procedures and codes of conduct which developed into the registered clinical trial protocols of today.
{"title":"Counting sheep: Louis Pasteur and the first registered public vaccine trial.","authors":"Cassandra Freitas,James A Hanley","doi":"10.1007/s10654-026-01367-5","DOIUrl":"https://doi.org/10.1007/s10654-026-01367-5","url":null,"abstract":"During the COVID-19 pandemic, vaccine development took center stage in the media and minds of the global community. This same daily scrutiny was also applied to the first public registered vaccine trial of anthrax prevention among livestock led by French scientist Louis Pasteur in 1881. At a meeting with the president of the Agricultural Society of Melun, Pasteur outlined what might be considered the first \"registered\" vaccine trial protocol. The trial proposed a three-arm trial where anthrax-naïve sheep (n = 60) and cows (n = 10) would be assigned either to a treatment group consisting of a 2-dose anthrax vaccination in addition to an anthrax challenge, a control group consisting of an unvaccinated group given the anthrax challenge or a second control group which received neither vaccine nor anthrax challenge. All vaccinated sheep and cows were alive 48 h post-challenge. All unvaccinated sheep who received the anthrax challenge died within 48 h post-challenge, and the unvaccinated cows developed large edemas at the site of inoculation. Witnessing the 100% efficacy of Pasteur's vaccine were hundreds of, mostly skeptical, onlookers including journalists who disseminated the big news across Europe within days. Two months later, the results of the trial reached North America, via attendees who had heard Pasteur's address at the International Medical Congress in London in August 1881. Pasteur's anthrax vaccine trial laid the foundations for the systematic, public, and a priori reporting of clinical trial procedures and codes of conduct which developed into the registered clinical trial protocols of today.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"77 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056889","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 : 2026-01-24DOI: 10.1007/s10654-025-01344-4
Estelle Ioannidou,Dagfinn Aune,Ioannis Theodosopoulos,Alicia K Heath
Circulating lipids are potentially modifiable risk factors for aortic aneurysm, however, associations between levels of specific lipids and aortic aneurysm are unclear. We analysed associations between blood lipids and aortic aneurysm in the UK Biobank and summarized the available data in a systematic review and meta-analysis of published cohort studies. Up to 429,610 participants aged 38-73 years at baseline in 2006-2010 in UK Biobank were included. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between serum/plasma lipids (total cholesterol, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, and lipoprotein(a)) and risk of aortic aneurysm. PubMed and Embase databases were searched up to November 11th, 2025, to identify relevant cohort studies. Random-effects models were used to estimate summary relative risks (RRs) and 95% CIs for the associations between blood lipid levels and aortic aneurysm risk. In UK Biobank, 2,434 aortic aneurysm cases occurred during 12.3 years of follow-up. Positive associations were observed between the highest vs. lowest quintile of total cholesterol (HR 1.22, 95% CI 1.07-1.41), LDL cholesterol (1.39, 1.21-1.60), apolipoprotein B (1.52, 1.33-1.74), non-HDL cholesterol (1.50, 1.29-1.73), triglycerides (1.23, 1.06-1.42), lipoprotein(a) (1.34, 1.17-1.54) and aortic aneurysm risk, while HDL cholesterol (0.57, 0.48-0.67) and apolipoprotein A1 (0.54, 0.46-0.63) were inversely associated. Eighteen cohort studies were included in the meta-analysis. The summary RR (95% CI) per 1 mmol/L increase was 1.16 (1.10-1.22, I2 = 74%, n = 15) for total cholesterol, 1.11 (1.04-1.19,I2 = 63%, n = 4) for LDL cholesterol, 1.28 (0.98-1.67, I2 = 89%, n = 2) for non-HDL cholesterol, 0.59 (0.50-0.70, I2 = 72%, n = 5) for HDL cholesterol, 1.02 (0.95-1.10, I2 = 55%, n = 7) for triglycerides, and 1.34 (1.17-1.55, I2 = 57%, n = 4) per 50 mg/dl incrememt in lipoprotein(a). Additional positive (apolipoprotein B, non-HDL cholesterol) and inverse (apolipoprotein A1) associations were observed in high vs. low meta-analyses. These findings suggest higher levels of total cholesterol, LDL cholesterol, apolipoprotein B, non-HDL cholesterol, lipoprotein(a), and possibly triglycerides are associated with increased risk of aortic aneurysm, while higher levels of HDL cholesterol and apolipoprotein A1 are associated with lower risk.
循环脂质是潜在的可改变的主动脉瘤危险因素，然而，特定脂质水平与主动脉瘤之间的关系尚不清楚。我们分析了UK Biobank中血脂和主动脉瘤之间的关系，并对已发表的队列研究进行了系统回顾和荟萃分析，总结了现有数据。在2006-2010年，英国生物银行的429,610名38-73岁的参与者被纳入基线。多变量Cox回归用于估计血清/血浆脂质（总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酸酯、载脂蛋白A1、载脂蛋白B和脂蛋白(a)）与主动脉瘤风险之间的风险比（hr）和95%置信区间（CIs）。检索截至2025年11月11日的PubMed和Embase数据库，以确定相关的队列研究。使用随机效应模型来估计血脂水平与主动脉瘤风险之间的总相对风险（rr）和95% ci。在UK Biobank中，在12.3年的随访中发生了2434例主动脉瘤病例。总胆固醇（HR 1.22, 95% CI 1.07-1.41）、低密度脂蛋白胆固醇（1.39,1.21-1.60）、载脂蛋白B（1.52, 1.33-1.74）、非高密度脂蛋白胆固醇（1.50,1.29-1.73）、甘油三酯（1.23,1.06-1.42）、脂蛋白(a)（1.34, 1.17-1.54）与主动脉瘤风险呈负相关，而高密度脂蛋白胆固醇（0.57,0.48-0.67）和载脂蛋白A1（0.54, 0.46-0.63）呈负相关。荟萃分析纳入了18项队列研究。摘要RR (95% CI)每增加1更易与L为1.16 (1.10 - -1.22,I2 = 74%, n = 15)总胆固醇,1.11 (1.04 - -1.19,I2 = 63%, n = 4)对低密度脂蛋白胆固醇,1.28 (0.98 - -1.67,I2 = 89%, n = 2) non-HDL胆固醇,0.59 (0.50 - -0.70,I2 = 72%, n = 5)高密度脂蛋白胆固醇,1.02 (0.95 - -1.10,I2 = 55%, n = 7)甘油三酸酯,和1.34 (1.17 - -1.55,I2 = 57%, n = 4)每50 mg / dl incrememt脂蛋白(a)。在高与低荟萃分析中观察到额外的阳性（载脂蛋白B，非高密度脂蛋白胆固醇）和反向（载脂蛋白A1）关联。这些发现表明，高水平的总胆固醇、低密度脂蛋白、载脂蛋白B、非高密度脂蛋白胆固醇、脂蛋白(a)以及可能的甘油三酯与动脉瘤风险增加有关，而高水平的高密度脂蛋白胆固醇和载脂蛋白A1与风险较低有关。
{"title":"Blood lipids and the risk of aortic aneurysm: results from the UK Biobank study and a systematic review and meta-analysis of cohort studies.","authors":"Estelle Ioannidou,Dagfinn Aune,Ioannis Theodosopoulos,Alicia K Heath","doi":"10.1007/s10654-025-01344-4","DOIUrl":"https://doi.org/10.1007/s10654-025-01344-4","url":null,"abstract":"Circulating lipids are potentially modifiable risk factors for aortic aneurysm, however, associations between levels of specific lipids and aortic aneurysm are unclear. We analysed associations between blood lipids and aortic aneurysm in the UK Biobank and summarized the available data in a systematic review and meta-analysis of published cohort studies. Up to 429,610 participants aged 38-73 years at baseline in 2006-2010 in UK Biobank were included. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between serum/plasma lipids (total cholesterol, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, and lipoprotein(a)) and risk of aortic aneurysm. PubMed and Embase databases were searched up to November 11th, 2025, to identify relevant cohort studies. Random-effects models were used to estimate summary relative risks (RRs) and 95% CIs for the associations between blood lipid levels and aortic aneurysm risk. In UK Biobank, 2,434 aortic aneurysm cases occurred during 12.3 years of follow-up. Positive associations were observed between the highest vs. lowest quintile of total cholesterol (HR 1.22, 95% CI 1.07-1.41), LDL cholesterol (1.39, 1.21-1.60), apolipoprotein B (1.52, 1.33-1.74), non-HDL cholesterol (1.50, 1.29-1.73), triglycerides (1.23, 1.06-1.42), lipoprotein(a) (1.34, 1.17-1.54) and aortic aneurysm risk, while HDL cholesterol (0.57, 0.48-0.67) and apolipoprotein A1 (0.54, 0.46-0.63) were inversely associated. Eighteen cohort studies were included in the meta-analysis. The summary RR (95% CI) per 1 mmol/L increase was 1.16 (1.10-1.22, I2 = 74%, n = 15) for total cholesterol, 1.11 (1.04-1.19,I2 = 63%, n = 4) for LDL cholesterol, 1.28 (0.98-1.67, I2 = 89%, n = 2) for non-HDL cholesterol, 0.59 (0.50-0.70, I2 = 72%, n = 5) for HDL cholesterol, 1.02 (0.95-1.10, I2 = 55%, n = 7) for triglycerides, and 1.34 (1.17-1.55, I2 = 57%, n = 4) per 50 mg/dl incrememt in lipoprotein(a). Additional positive (apolipoprotein B, non-HDL cholesterol) and inverse (apolipoprotein A1) associations were observed in high vs. low meta-analyses. These findings suggest higher levels of total cholesterol, LDL cholesterol, apolipoprotein B, non-HDL cholesterol, lipoprotein(a), and possibly triglycerides are associated with increased risk of aortic aneurysm, while higher levels of HDL cholesterol and apolipoprotein A1 are associated with lower risk.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"56 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033688","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 : 2026-01-24DOI: 10.1007/s10654-025-01359-x
Jacques Hilbert,Fernando Topfstedt,Laura Matuschik,Lars Schmitt,Ilaria Panzeri,John Andrew Pospisilik,Gabriel Seifert
Early-onset colorectal cancer (eoCRC), defined by diagnosis before age 50, is increasing worldwide. Metabolic disorders are suspected contributors. We performed a systematic review and meta-analysis to quantify associations between eoCRC and obesity, type 2 diabetes, hyperlipidemia, arterial hypertension and metabolic syndrome. We systematically searched MEDLINE, Cochrane Central Register of systematic reviews, EMBASE, ClinicalTrials.gov, and Web of Science from March 2023 to December 2024. A univariate meta-analysis was performed for outcomes with at least four studies and comparable means of association. 38 studies were included. Obesity at diagnosis was associated significantly with a 1.45-fold increased risk of eoCRC. Elevated BMI during late adolescence, at age 20, and at age 30 were associated with higher eoCRC risk in multiple cohort studies. as independent risk factors. Among male individuals aged 20-49, Type 2 diabetes increased eoCRC risk, with affected individuals exhibiting a 10-year colorectal cancer risk comparable to that of the general population at age 50,but occurring 4-5 years earlier. Additional positive associations were reported for hyperlipidemia (ages 20-39), arterial hypertension in males (ages 20-39), and metabolic syndrome, although findings were heterogeneous. A higher number of metabolic comorbidities was positively correlated with increased eoCRC risk. Early metabolic dysregulation appears to accelerate colorectal carcinogenesis, increasing the impact of metabolic risk factors at younger ages. As metabolic disorders rise among adolescents and young adults, the eoCRC burden likely will grow. Life-course studies integrating metabolic trajectories, molecular biomarkers, epidemiologic data while accounting for screening exposure are needed to clarify causal pathways and guide prevention and screening.
早发性结直肠癌（eoCRC）在全球范围内呈上升趋势。代谢紊乱被怀疑是原因之一。我们进行了系统回顾和荟萃分析，以量化eoCRC与肥胖、2型糖尿病、高脂血症、动脉高血压和代谢综合征之间的关系。从2023年3月到2024年12月，我们系统地检索了MEDLINE、Cochrane Central Register of systematic reviews、EMBASE、ClinicalTrials.gov和Web of Science。对至少有四项研究的结果和可比较的关联方法进行单变量荟萃分析。纳入了38项研究。诊断时肥胖与eoCRC风险增加1.45倍显著相关。在多队列研究中，青春期晚期、20岁和30岁时BMI升高与eoCRC风险升高相关。作为独立的风险因素。在20-49岁的男性个体中，2型糖尿病增加了eoCRC风险，受影响的个体在10年内患结直肠癌的风险与50岁的普通人群相当，但发生时间早4-5年。另外，高脂血症（20-39岁）、男性动脉高血压（20-39岁）和代谢综合征也有正相关的报道，尽管结果不尽相同。较高的代谢合并症数量与eoCRC风险增加正相关。早期代谢失调似乎会加速结直肠癌的发生，增加年轻时代谢危险因素的影响。随着代谢性疾病在青少年和年轻人中的增加，eoCRC的负担可能会增加。需要在考虑筛查暴露的同时，整合代谢轨迹、分子生物标志物、流行病学数据的生命过程研究，以阐明因果途径，指导预防和筛查。
{"title":"Early-onset colorectal cancer is associated with metabolic disorders: a systematic review and meta-analysis.","authors":"Jacques Hilbert,Fernando Topfstedt,Laura Matuschik,Lars Schmitt,Ilaria Panzeri,John Andrew Pospisilik,Gabriel Seifert","doi":"10.1007/s10654-025-01359-x","DOIUrl":"https://doi.org/10.1007/s10654-025-01359-x","url":null,"abstract":"Early-onset colorectal cancer (eoCRC), defined by diagnosis before age 50, is increasing worldwide. Metabolic disorders are suspected contributors. We performed a systematic review and meta-analysis to quantify associations between eoCRC and obesity, type 2 diabetes, hyperlipidemia, arterial hypertension and metabolic syndrome. We systematically searched MEDLINE, Cochrane Central Register of systematic reviews, EMBASE, ClinicalTrials.gov, and Web of Science from March 2023 to December 2024. A univariate meta-analysis was performed for outcomes with at least four studies and comparable means of association. 38 studies were included. Obesity at diagnosis was associated significantly with a 1.45-fold increased risk of eoCRC. Elevated BMI during late adolescence, at age 20, and at age 30 were associated with higher eoCRC risk in multiple cohort studies. as independent risk factors. Among male individuals aged 20-49, Type 2 diabetes increased eoCRC risk, with affected individuals exhibiting a 10-year colorectal cancer risk comparable to that of the general population at age 50,but occurring 4-5 years earlier. Additional positive associations were reported for hyperlipidemia (ages 20-39), arterial hypertension in males (ages 20-39), and metabolic syndrome, although findings were heterogeneous. A higher number of metabolic comorbidities was positively correlated with increased eoCRC risk. Early metabolic dysregulation appears to accelerate colorectal carcinogenesis, increasing the impact of metabolic risk factors at younger ages. As metabolic disorders rise among adolescents and young adults, the eoCRC burden likely will grow. Life-course studies integrating metabolic trajectories, molecular biomarkers, epidemiologic data while accounting for screening exposure are needed to clarify causal pathways and guide prevention and screening.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"87 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033692","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 : 2026-01-24DOI: 10.1007/s10654-025-01334-6
Isabel A L Slurink, Annemarijn R de Boer, Marc J M Bonten, Miriam C J M Sturkenboom, Patricia C J L Bruijning-Verhagen
Excess mortality during the COVID-19 pandemic partly exceeded COVID-19-related deaths, indicating that other causes may have contributed. We conducted a retrospective data-linkage study including all Dutch inhabitants to investigate the impact of COVID-19 vaccination on excess mortality using a modified self-controlled case series method. We found a 44% lower relative incidence of all-cause deaths in the first three weeks after the primary vaccination compared to more than three weeks after vaccination (IRR 0.56, 95%CI 0.54-0.57). This lower incidence was consistent across vaccine types, doses, genders, age groups, and individuals with or without prior SARS-CoV-2 infection or comorbidities, and for non-COVID-19 related deaths. For booster vaccinations, the relative incidence was similar (IRR 0.49, 95%CI 0.49-0.50). In comparison, we observed a 16-fold higher incidence of all-cause deaths in the three weeks following a registered positive SARS-CoV-2 infection compared to more than three weeks after infection (IRR 16.19, 95%CI 15.78-16.60). A lower relative incidence of short-term deaths following COVID-19 vaccination support that COVID-19 vaccination is not associated with the observed excess mortality.
{"title":"COVID-19 vaccination and short-term mortality risk: a nationwide self-controlled case series study in The Netherlands.","authors":"Isabel A L Slurink, Annemarijn R de Boer, Marc J M Bonten, Miriam C J M Sturkenboom, Patricia C J L Bruijning-Verhagen","doi":"10.1007/s10654-025-01334-6","DOIUrl":"https://doi.org/10.1007/s10654-025-01334-6","url":null,"abstract":"<p><p>Excess mortality during the COVID-19 pandemic partly exceeded COVID-19-related deaths, indicating that other causes may have contributed. We conducted a retrospective data-linkage study including all Dutch inhabitants to investigate the impact of COVID-19 vaccination on excess mortality using a modified self-controlled case series method. We found a 44% lower relative incidence of all-cause deaths in the first three weeks after the primary vaccination compared to more than three weeks after vaccination (IRR 0.56, 95%CI 0.54-0.57). This lower incidence was consistent across vaccine types, doses, genders, age groups, and individuals with or without prior SARS-CoV-2 infection or comorbidities, and for non-COVID-19 related deaths. For booster vaccinations, the relative incidence was similar (IRR 0.49, 95%CI 0.49-0.50). In comparison, we observed a 16-fold higher incidence of all-cause deaths in the three weeks following a registered positive SARS-CoV-2 infection compared to more than three weeks after infection (IRR 16.19, 95%CI 15.78-16.60). A lower relative incidence of short-term deaths following COVID-19 vaccination support that COVID-19 vaccination is not associated with the observed excess mortality.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040269","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 : 2026-01-24DOI: 10.1007/s10654-025-01353-3
Aleksandra Saulicz,David Abernethy,Darren Wraith
A considerable number of studies have highlighted that engaging in physical activity (PA) improves health and reduces risk of mortality. But is there a limit? Some evidence suggests a U-shaped exposure-response in which the protective benefits of strenuous exercise eventually diminish (at some point) and the risk of a cardiovascular event or death increases, thereby questioning a linear association between exercise volume, intensity, and cardiovascular events/mortality. This review evaluates the evidence and critically appraises studies assessing whether strenuous exercise is associated with increased cardiovascular-related events from an epidemiological perspective. After a comprehensive literature search, 1,908 records were identified; 1,068 remained after deduplication. Title/abstract screening excluded 950 records; 66 full texts were assessed; 14 studies were included for critical review. Two independent assessors appraised study quality and risk of bias, focusing on exposure and outcome measurement, confounder control, and whether timeframes and follow-up were adequate to observe associations. Evidence supporting a U-shaped exposure-response was limited. No study achieved the highest quality rating. Common limitations included inconsistent intensity classification, absence of repeated exposure measurement, inconsistencies with outcome measures, insufficient follow-up to capture long-term effects, and incomplete adjustment for key confounders. The current evidence supports the benefits of regular PA, including strenuous activity, with benefits appearing to plateau at very high doses. Further rigorous epidemiological research with repeated exposure measures, standardised outcomes, adequate follow-up, and more robust control for confounding is needed.
{"title":"Can too much exercise kill you? A systematic review of the risk of a cardiovascular event or death from long term strenuous exercise.","authors":"Aleksandra Saulicz,David Abernethy,Darren Wraith","doi":"10.1007/s10654-025-01353-3","DOIUrl":"https://doi.org/10.1007/s10654-025-01353-3","url":null,"abstract":"A considerable number of studies have highlighted that engaging in physical activity (PA) improves health and reduces risk of mortality. But is there a limit? Some evidence suggests a U-shaped exposure-response in which the protective benefits of strenuous exercise eventually diminish (at some point) and the risk of a cardiovascular event or death increases, thereby questioning a linear association between exercise volume, intensity, and cardiovascular events/mortality. This review evaluates the evidence and critically appraises studies assessing whether strenuous exercise is associated with increased cardiovascular-related events from an epidemiological perspective. After a comprehensive literature search, 1,908 records were identified; 1,068 remained after deduplication. Title/abstract screening excluded 950 records; 66 full texts were assessed; 14 studies were included for critical review. Two independent assessors appraised study quality and risk of bias, focusing on exposure and outcome measurement, confounder control, and whether timeframes and follow-up were adequate to observe associations. Evidence supporting a U-shaped exposure-response was limited. No study achieved the highest quality rating. Common limitations included inconsistent intensity classification, absence of repeated exposure measurement, inconsistencies with outcome measures, insufficient follow-up to capture long-term effects, and incomplete adjustment for key confounders. The current evidence supports the benefits of regular PA, including strenuous activity, with benefits appearing to plateau at very high doses. Further rigorous epidemiological research with repeated exposure measures, standardised outcomes, adequate follow-up, and more robust control for confounding is needed.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"55 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033779","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 : 2026-01-24DOI: 10.1007/s10654-025-01349-z
Emilio A L Gianicolo,Maria Blettner,Andreas Stang
{"title":"Indirect standardization: time to eliminate misleading terminology.","authors":"Emilio A L Gianicolo,Maria Blettner,Andreas Stang","doi":"10.1007/s10654-025-01349-z","DOIUrl":"https://doi.org/10.1007/s10654-025-01349-z","url":null,"abstract":"","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"66 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033689","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 : 2026-01-24DOI: 10.1007/s10654-025-01347-1
Marta Pineda-Moncusí,Maria Rahman,Eleanor L Axson,Susan Hodgson,Antonella Delmestri
Since its establishment in the late 1980s, the UK Clinical Practice Research Datalink (CPRD) has become one of the most widely utilised data resources in both national and international research. Its value lies in the richness, scale and quality of its routinely collected primary care data, as well as the availability of numerous linkable datasets. This study provides comprehensive scientometric analyses of CPRD-related research output, impact, and data usage from 1988 to 2024. A total of 3779 peer-reviewed publications were identified, and for 98.78% of them, enriched bibliometric metadata were retrieved through Scopus and Web of Science. The UK emerged as the leading contributing country, with the United States and Canada ranking second and third. 'McGill University' was the most frequently affiliated institution, followed by the 'University of Manchester' and the 'University of Oxford', with seven UK universities among the top ten. The three journals most frequently publishing CPRD-based research overall, and since 2020, were 'BMJ Open', 'Pharmacoepidemiology and Drug Safety' and 'British Journal of General Practice'. Analyses of primary care data sources utilisation revealed that overall, 86.35% of manuscripts used CPRD GOLD exclusively, 8.39% used both CPRD GOLD and CPRD Aurum, and 4.76% used CPRD Aurum alone, although recent years showed an increased use of CPRD Aurum. Between 2016 and 2024, most articles (80.26%) were associated with CPRD research applications that referenced linked or CPRD algorithm-derived datasets. The three most frequently used were 'Hospital Episode Statistics' (69.77%), 'Small Area Linkages' (62.27%) and 'Office for National Statistics' mortality data (53.28%).
自20世纪80年代末建立以来，英国临床实践研究数据链（CPRD）已成为国内和国际研究中使用最广泛的数据资源之一。它的价值在于其常规收集的初级保健数据的丰富性、规模和质量，以及大量可链接数据集的可用性。本研究对1988 - 2024年cprd相关研究产出、影响和数据使用情况进行了全面的科学计量分析。共发现3779篇同行评议出版物，其中98.78%通过Scopus和Web of Science检索到丰富的文献计量元数据。英国成为贡献最多的国家，美国和加拿大分列第二和第三位。麦吉尔大学（McGill University）是排名最靠前的大学，其次是曼彻斯特大学（University of Manchester）和牛津大学（University of Oxford），共有7所英国大学跻身前十。总体而言，自2020年以来最常发表基于cpr的研究的三个期刊是“BMJ Open”、“Pharmacoepidemiology and Drug Safety”和“British Journal of General Practice”。对初级保健数据来源利用情况的分析显示，总体而言，86.35%的手稿只使用CPRD GOLD， 8.39%同时使用CPRD GOLD和CPRD Aurum， 4.76%单独使用CPRD Aurum，尽管近年来CPRD Aurum的使用有所增加。2016年至2024年间，大多数文章（80.26%）与引用链接或CPRD算法衍生数据集的CPRD研究应用相关。最常用的三个词是“医院事件统计”（69.77%）、“小区域联系”（62.27%）和“国家统计局死亡率数据”（53.28%）。
{"title":"Academic impact and research data utilisation of the clinical practice research datalink: scientometric analyses.","authors":"Marta Pineda-Moncusí,Maria Rahman,Eleanor L Axson,Susan Hodgson,Antonella Delmestri","doi":"10.1007/s10654-025-01347-1","DOIUrl":"https://doi.org/10.1007/s10654-025-01347-1","url":null,"abstract":"Since its establishment in the late 1980s, the UK Clinical Practice Research Datalink (CPRD) has become one of the most widely utilised data resources in both national and international research. Its value lies in the richness, scale and quality of its routinely collected primary care data, as well as the availability of numerous linkable datasets. This study provides comprehensive scientometric analyses of CPRD-related research output, impact, and data usage from 1988 to 2024. A total of 3779 peer-reviewed publications were identified, and for 98.78% of them, enriched bibliometric metadata were retrieved through Scopus and Web of Science. The UK emerged as the leading contributing country, with the United States and Canada ranking second and third. 'McGill University' was the most frequently affiliated institution, followed by the 'University of Manchester' and the 'University of Oxford', with seven UK universities among the top ten. The three journals most frequently publishing CPRD-based research overall, and since 2020, were 'BMJ Open', 'Pharmacoepidemiology and Drug Safety' and 'British Journal of General Practice'. Analyses of primary care data sources utilisation revealed that overall, 86.35% of manuscripts used CPRD GOLD exclusively, 8.39% used both CPRD GOLD and CPRD Aurum, and 4.76% used CPRD Aurum alone, although recent years showed an increased use of CPRD Aurum. Between 2016 and 2024, most articles (80.26%) were associated with CPRD research applications that referenced linked or CPRD algorithm-derived datasets. The three most frequently used were 'Hospital Episode Statistics' (69.77%), 'Small Area Linkages' (62.27%) and 'Office for National Statistics' mortality data (53.28%).","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"284 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033691","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 : 2026-01-24DOI: 10.1007/s10654-025-01356-0
Viktor H Ahlqvist, Hugo Sjöqvist, Arvid Sjölander, Daniel Berglind, Paul C Lambert, Brian K Lee, Paul Madley-Dowd
Findings from family-based analyses, such as sibling comparisons, are often reported using only odds ratios or hazard ratios. We demonstrate how this can be improved upon by applying the marginalized between-within framework. We provide an overview of sibling comparison methods and the marginalized between-within framework, which enables estimation of absolute risks and clinically relevant metrics while accounting for shared familial confounding. We illustrate the approach using Swedish registry data to examine the association between maternal smoking and infant mortality, estimating absolute quantities (e.g., cumulative risks), average treatment effects, attributable fractions, and numbers needed to harm (or treat). The marginalized between-within model decomposes effects into within- and between-family components while applying a global baseline across all families. Although it typically yields similar relative estimates to conditional logistic or stratified Cox regression, the model's specification of a baseline enables the estimation of absolute measures. In the applied example, absolute measures provided more interpretable and policy-relevant insights than relative estimates alone. Code for implementation in Stata and R is provided. The marginalized between-within framework may strengthen the interpretability of family-based analysis by enabling absolute and policy-relevant estimates for both binary and time-to-event outcomes, moving beyond the limitations of solely relying on relative effect measures.
{"title":"Moving beyond risk ratios in sibling analysis: estimating clinically useful measures from family-based analysis.","authors":"Viktor H Ahlqvist, Hugo Sjöqvist, Arvid Sjölander, Daniel Berglind, Paul C Lambert, Brian K Lee, Paul Madley-Dowd","doi":"10.1007/s10654-025-01356-0","DOIUrl":"10.1007/s10654-025-01356-0","url":null,"abstract":"<p><p>Findings from family-based analyses, such as sibling comparisons, are often reported using only odds ratios or hazard ratios. We demonstrate how this can be improved upon by applying the marginalized between-within framework. We provide an overview of sibling comparison methods and the marginalized between-within framework, which enables estimation of absolute risks and clinically relevant metrics while accounting for shared familial confounding. We illustrate the approach using Swedish registry data to examine the association between maternal smoking and infant mortality, estimating absolute quantities (e.g., cumulative risks), average treatment effects, attributable fractions, and numbers needed to harm (or treat). The marginalized between-within model decomposes effects into within- and between-family components while applying a global baseline across all families. Although it typically yields similar relative estimates to conditional logistic or stratified Cox regression, the model's specification of a baseline enables the estimation of absolute measures. In the applied example, absolute measures provided more interpretable and policy-relevant insights than relative estimates alone. Code for implementation in Stata and R is provided. The marginalized between-within framework may strengthen the interpretability of family-based analysis by enabling absolute and policy-relevant estimates for both binary and time-to-event outcomes, moving beyond the limitations of solely relying on relative effect measures.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040523","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}
Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease whose incidence increases with age. According to the gene-time-environment hypothesis, ALS onset occurs through the interaction between genes and environmental exposures during ageing, which may involve a continuous accumulation process. Alternatively, the multistep pathogenic hypothesis, based on the Armitage-Doll multistep model from cancer research, posits that a discrete number of specific sequential "hits" are necessary to trigger ALS. Here we analyzed three large population-based epidemiological datasets of ALS to formally test whether the ALS age-incidence curve is better described by a power law, as predicted by the Armitage-Doll model, or by an exponential function, which is generally associated to continuous accumulation of damage and is incompatible with the Armitage-Doll model. We obtained moderate-to-extreme Bayesian evidence in favor of the exponential function compared to the power law. Cancer data were instead better aligned, as expected, with the power law. These results suggest that the multistep pathogenesis hypothesis based on the Armitage-Doll model cannot be extended from cancer to ALS, because it is incompatible with the epidemiological data. This calls for a re-consideration of the current understanding of ALS pathogenesis. Our work also warns against extending the Armitage-Doll multistep model from cancer to other aging-related diseases solely based on age-incidence curves.
{"title":"The multistep pathogenic hypothesis of amyotrophic lateral sclerosis is incompatible with the epidemiological data.","authors":"Guglielmo Foffani,Daniele Urso,Josh Hiller,Marco Piccininni,Benoît Marin,Giancarlo Logroscino","doi":"10.1007/s10654-025-01289-8","DOIUrl":"https://doi.org/10.1007/s10654-025-01289-8","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease whose incidence increases with age. According to the gene-time-environment hypothesis, ALS onset occurs through the interaction between genes and environmental exposures during ageing, which may involve a continuous accumulation process. Alternatively, the multistep pathogenic hypothesis, based on the Armitage-Doll multistep model from cancer research, posits that a discrete number of specific sequential \"hits\" are necessary to trigger ALS. Here we analyzed three large population-based epidemiological datasets of ALS to formally test whether the ALS age-incidence curve is better described by a power law, as predicted by the Armitage-Doll model, or by an exponential function, which is generally associated to continuous accumulation of damage and is incompatible with the Armitage-Doll model. We obtained moderate-to-extreme Bayesian evidence in favor of the exponential function compared to the power law. Cancer data were instead better aligned, as expected, with the power law. These results suggest that the multistep pathogenesis hypothesis based on the Armitage-Doll model cannot be extended from cancer to ALS, because it is incompatible with the epidemiological data. This calls for a re-consideration of the current understanding of ALS pathogenesis. Our work also warns against extending the Armitage-Doll multistep model from cancer to other aging-related diseases solely based on age-incidence curves.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"39 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033690","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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