European Journal of Epidemiology最新文献

{"title":"Differences in metabolomic profiles between Black and White women in the U.S.: Analyses from two prospective cohorts","authors":"Emma E. McGee, Oana A. Zeleznik, Raji Balasubramanian, Jie Hu, Bernard A. Rosner, Jean Wactawski-Wende, Clary B. Clish, Julian Avila-Pacheco, Walter C. Willett, Kathryn M. Rexrode, Rulla M. Tamimi, A. Heather Eliassen","doi":"10.1007/s10654-024-01111-x","DOIUrl":"https://doi.org/10.1007/s10654-024-01111-x","url":null,"abstract":"<p>There is growing interest in incorporating metabolomics into public health practice. However, Black women are under-represented in many metabolomics studies. If metabolomic profiles differ between Black and White women, this under-representation may exacerbate existing Black-White health disparities. We therefore aimed to estimate metabolomic differences between Black and White women in the U.S. We leveraged data from two prospective cohorts: the Nurses’ Health Study (NHS; n = 2077) and Women’s Health Initiative (WHI; n = 2128). The WHI served as the replication cohort. Plasma metabolites (n = 334) were measured via liquid chromatography-tandem mass spectrometry. Observed metabolomic differences were estimated using linear regression and metabolite set enrichment analyses. Residual metabolomic differences in a hypothetical population in which the distributions of 14 risk factors were equalized across racial groups were estimated using inverse odds ratio weighting. In the NHS, Black-White differences were observed for most metabolites (75 metabolites with observed differences <span>(ge )</span>|0.50| standard deviations). Black women had lower average levels than White women for most metabolites (e.g., for N6, N6-dimethlylysine, mean Black-White difference = − 0.98 standard deviations; 95% CI: − 1.11, − 0.84). In metabolite set enrichment analyses, Black women had lower levels of triglycerides, phosphatidylcholines, lysophosphatidylethanolamines, phosphatidylethanolamines, and organoheterocyclic compounds, but higher levels of phosphatidylethanolamine plasmalogens, phosphatidylcholine plasmalogens, cholesteryl esters, and carnitines. In a hypothetical population in which distributions of 14 risk factors were equalized, Black-White metabolomic differences persisted. Most results replicated in the WHI (88% of 272 metabolites available for replication). Substantial differences in metabolomic profiles exist between Black and White women. Future studies should prioritize racial representation.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"66 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846112","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 Chinese keratoconus (CKC) cohort study","authors":"Kaili Yang, Xiaotian Liu, Liyan Xu, Yuwei Gu, Qi Fan, Shanshan Yin, Yifan Wang, Yi Yuan, Anqi Chang, Yonghao Zang, Chenchen Yin, Chenjiu Pang, Chongjian Wang, Shengwei Ren","doi":"10.1007/s10654-024-01128-2","DOIUrl":"https://doi.org/10.1007/s10654-024-01128-2","url":null,"abstract":"<p>The Chinese keratoconus (CKC) cohort study is a population-based longitudinal prospective cohort study in the Chinese population involving a clinical database and biobanks. This ongoing study focuses on the prevention of KC progression and is the first to involve the effect of gene‒environment interactions on KC progression. The CKC cohort is hospital-based and dynamic and was established in Zhengzhou, China; KC patients (<i>n</i> = 1114) from a large geographical area were enrolled from January 2019 to June 2023, with a mean age of 22.23 years (6‒57 years). Demographic details, socioeconomic characteristics, lifestyle, disease history, surgical history, family history, and visual and social function data are being collected using questionnaires. General physical examination, eye examination, biological specimen collection, and first-degree relative data were collected and analyzed in the present study. The primary focus of the present study was placed on gene, environment and the effect of gene‒environment interactions on KC progression. The follow-up of the CKC cohort study is expected to include data collection at 3 months, 6 months, and 1 year after the initial examination and then at the annual follow-up examinations. The first follow-up of the CKC cohort study was recorded. A total of 918 patients completed the follow-up by June 1, 2023, with a response rate of 82.40%. Aside from the younger age of patients who were followed up, no significant differences were found between patients who were followed up and patients who were not.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"5 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846116","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":"Differences in metabolomic profiles between Black and White women in the U.S.: Analyses from two prospective cohorts.","authors":"Emma E McGee, Oana A Zeleznik, Raji Balasubramanian, Jie Hu, Bernard A Rosner, Jean Wactawski-Wende, Clary B Clish, Julian Avila-Pacheco, Walter C Willett, Kathryn M Rexrode, Rulla M Tamimi, A Heather Eliassen","doi":"10.1007/s10654-024-01111-x","DOIUrl":"https://doi.org/10.1007/s10654-024-01111-x","url":null,"abstract":"<p><p>There is growing interest in incorporating metabolomics into public health practice. However, Black women are under-represented in many metabolomics studies. If metabolomic profiles differ between Black and White women, this under-representation may exacerbate existing Black-White health disparities. We therefore aimed to estimate metabolomic differences between Black and White women in the U.S. We leveraged data from two prospective cohorts: the Nurses' Health Study (NHS; n = 2077) and Women's Health Initiative (WHI; n = 2128). The WHI served as the replication cohort. Plasma metabolites (n = 334) were measured via liquid chromatography-tandem mass spectrometry. Observed metabolomic differences were estimated using linear regression and metabolite set enrichment analyses. Residual metabolomic differences in a hypothetical population in which the distributions of 14 risk factors were equalized across racial groups were estimated using inverse odds ratio weighting. In the NHS, Black-White differences were observed for most metabolites (75 metabolites with observed differences <math><mo>≥</mo></math> |0.50| standard deviations). Black women had lower average levels than White women for most metabolites (e.g., for N6, N6-dimethlylysine, mean Black-White difference = - 0.98 standard deviations; 95% CI: - 1.11, - 0.84). In metabolite set enrichment analyses, Black women had lower levels of triglycerides, phosphatidylcholines, lysophosphatidylethanolamines, phosphatidylethanolamines, and organoheterocyclic compounds, but higher levels of phosphatidylethanolamine plasmalogens, phosphatidylcholine plasmalogens, cholesteryl esters, and carnitines. In a hypothetical population in which distributions of 14 risk factors were equalized, Black-White metabolomic differences persisted. Most results replicated in the WHI (88% of 272 metabolites available for replication). Substantial differences in metabolomic profiles exist between Black and White women. Future studies should prioritize racial representation.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853737","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":"Antihypertensive drug targets and breast cancer risk: a two-sample Mendelian randomization study.","authors":"Guoqiao Zheng, Subhayan Chattopadhyay, Jan Sundquist, Kristina Sundquist, Jianguang Ji","doi":"10.1007/s10654-024-01103-x","DOIUrl":"10.1007/s10654-024-01103-x","url":null,"abstract":"<p><p>Findings on the correlation between the use of antihypertensive medication and the risk of breast cancer (BC) have been inconsistent. We performed a two-sample Mendelian randomization (MR) using instrumental variables to proxy changes in gene expressions of antihypertensive medication targets to interrogate this. Genetic instruments for expression of antihypertensive drug target genes were identified with expression quantitative trait loci in blood, which should be associated with systolic blood pressure to proxy for the effect of antihypertensive drug. The association between genetic variants and BC risk were obtained from genome-wide association study summary statistics. The summary-based MR was employed to estimate the drug effects on BC risk. We further performed sensitivity analyses to confirm the discovered MR associations such as assessment of horizontal pleiotropy, colocalization, and multiple tissue enrichment analyses. The overall BC risk was only associated with SLC12A2 gene expression at a Bonferroni-corrected threshold. One standard deviation (SD) decrease of SLC12A2 gene expression in blood was associated with a decrease of 1.12 (95%CI, 0.80-1.58) mmHg of systolic blood pressure, but a 16% increased BC risk (odds ratio, 1.16, 95% confidential interval, 1.06-1.28). This signal was further observed for estrogen receptor positive (ER +) BC (1.17, 1.06-1.28). In addition, one SD decrease in expression of PDE1B in blood was associated with 7% decreased risk of ER + BC (0.93, 0.90-0.97). We detected no evidence of horizontal pleiotropy for these associations and the probability of the causal variants being shared between the gene expression and BC risk was 81.5, 40.5 and 66.8%, respectively. No significant association was observed between other target gene expressions and BC risk. Changes in expression of SLC12A2 and PDE1B mediated possibly via antihypertensive drugs may result in increased and decreased BC risk, respectively.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"535-548"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139939844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of the instrumental inequalities in simulated mendelian randomization analyses with coarsened exposures.","authors":"Elizabeth W Diemer, Joy Shi, Miguel A Hernan, Sonja A Swanson","doi":"10.1007/s10654-024-01130-8","DOIUrl":"10.1007/s10654-024-01130-8","url":null,"abstract":"<p><p>Mendelian randomization (MR) requires strong unverifiable assumptions to estimate causal effects. However, for categorical exposures, the MR assumptions can be falsified using a method known as the instrumental inequalities. To apply the instrumental inequalities to a continuous exposure, investigators must coarsen the exposure, a process which can itself violate the MR conditions. Violations of the instrumental inequalities for an MR model with a coarsened exposure might therefore reflect the effect of coarsening rather than other sources of bias. We aim to evaluate how exposure coarsening affects the ability of the instrumental inequalities to detect bias in MR models with multiple proposed instruments under various causal structures. To do so, we simulated data mirroring existing studies of the effect of alcohol consumption on cardiovascular disease under a variety of exposure-outcome effects in which the MR assumptions were met for a continuous exposure. We categorized the exposure based on subject matter knowledge or the observed data distribution and applied the instrumental inequalities to MR models for the effects of the coarsened exposure. In simulations of multiple binary instruments, the instrumental inequalities did not detect bias under any magnitude of exposure outcome effect when the exposure was coarsened into more than 2 categories. However, in simulations of both single and multiple proposed instruments, the instrumental inequalities were violated in some scenarios when the exposure was dichotomized. The results of these simulations suggest that the instrumental inequalities are largely insensitive to bias due to exposure coarsening with greater than 2 categories, and could be used with coarsened exposures to evaluate the required assumptions in applied MR studies, even when the underlying exposure is truly continuous.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"491-499"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179044","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":"Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review.","authors":"Grace M Power, Eleanor Sanderson, Panagiota Pagoni, Abigail Fraser, Tim Morris, Claire Prince, Timothy M Frayling, Jon Heron, Tom G Richardson, Rebecca Richmond, Jessica Tyrrell, Nicole Warrington, George Davey Smith, Laura D Howe, Kate M Tilling","doi":"10.1007/s10654-023-01032-1","DOIUrl":"10.1007/s10654-023-01032-1","url":null,"abstract":"<p><p>Diseases diagnosed in adulthood may have antecedents throughout (including prenatal) life. Gaining a better understanding of how exposures at different stages in the lifecourse influence health outcomes is key to elucidating the potential benefits of disease prevention strategies. Mendelian randomisation (MR) is increasingly used to estimate causal effects of exposures across the lifecourse on later life outcomes. This systematic literature review explores MR methods used to perform lifecourse investigations and reviews previous work that has utilised MR to elucidate the effects of factors acting at different stages of the lifecourse. We conducted searches in PubMed, Embase, Medline and MedRXiv databases. Thirteen methodological studies were identified. Four studies focused on the impact of time-varying exposures in the interpretation of \"standard\" MR techniques, five presented methods for repeat measures of the same exposure, and four described methodological approaches to handling multigenerational exposures. A further 127 studies presented the results of an applied research question. Over half of these estimated effects in a single generation and were largely confined to the exploration of questions regarding body composition. The remaining mostly estimated maternal effects. There is a growing body of research focused on the development and application of MR methods to address lifecourse research questions. The underlying assumptions require careful consideration and the interpretation of results rely on select conditions. Whilst we do not advocate for a particular strategy, we encourage practitioners to make informed decisions on how to approach a research question in this field with a solid understanding of the limitations present and how these may be affected by the research question, modelling approach, instrument selection, and data availability.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"501-520"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-linear Mendelian randomization: detection of biases using negative controls with a focus on BMI, Vitamin D and LDL cholesterol.","authors":"Fergus W Hamilton, David A Hughes, Wes Spiller, Kate Tilling, George Davey Smith","doi":"10.1007/s10654-024-01113-9","DOIUrl":"10.1007/s10654-024-01113-9","url":null,"abstract":"<p><p>Mendelian randomisation (MR) is an established technique in epidemiological investigation, using the principle of random allocation of genetic variants at conception to estimate the causal linear effect of an exposure on an outcome. Extensions to this technique include non-linear approaches that allow for differential effects of the exposure on the outcome depending on the level of the exposure. A widely used non-linear method is the residual approach, which estimates the causal effect within different strata of the non-genetically predicted exposure (i.e. the \"residual\" exposure). These \"local\" causal estimates are then used to make inferences about non-linear effects. Recent work has identified that this method can lead to estimates that are seriously biased, and a new method-the doubly-ranked method-has been introduced as a possibly more robust approach. In this paper, we perform negative control outcome analyses in the MR context. These are analyses with outcomes onto which the exposure should have no predicted causal effect. Using both methods we find clearly biased estimates in certain situations. We additionally examined a situation for which there are robust randomised controlled trial estimates of effects-that of low-density lipoprotein cholesterol (LDL-C) reduction onto myocardial infarction, where randomised trials have provided strong evidence of the shape of the relationship. The doubly-ranked method did not identify the same shape as the trial data, and for LDL-C and other lipids they generated some highly implausible findings. Therefore, we suggest there should be extensive simulation and empirical methodological examination of performance of both methods for NLMR under different conditions before further use of these methods. In the interim, use of NLMR methods needs justification, and a number of sanity checks (such as analysis of negative and positive control outcomes, sensitivity analyses excluding removal of strata at the extremes of the distribution, examination of biological plausibility and triangulation of results) should be performed.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"451-465"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D and human health: evidence from Mendelian randomization studies.","authors":"Aiping Fang, Yue Zhao, Ping Yang, Xuehong Zhang, Edward L Giovannucci","doi":"10.1007/s10654-023-01075-4","DOIUrl":"10.1007/s10654-023-01075-4","url":null,"abstract":"<p><p>We summarized the current evidence on vitamin D and major health outcomes from Mendelian randomization (MR) studies. PubMed and Embase were searched for original MR studies on vitamin D in relation to any health outcome from inception to September 1, 2022. Nonlinear MR findings were excluded due to concerns about the validity of the statistical methods used. A meta-analysis was preformed to synthesize study-specific estimates after excluding overlapping samples, where applicable. The methodological quality of the included studies was evaluated according to the STROBE-MR checklist. A total of 133 MR publications were eligible for inclusion in the analyses. The causal association between vitamin D status and 275 individual outcomes was examined. Linear MR analyses showed genetically high 25-hydroxyvitamin D (25(OH)D) concentrations were associated with reduced risk of multiple sclerosis incidence and relapse, non-infectious uveitis and scleritis, psoriasis, femur fracture, leg fracture, amyotrophic lateral sclerosis, anorexia nervosa, delirium, heart failure, ovarian cancer, non-alcoholic fatty liver disease, dyslipidemia, and bacterial pneumonia, but increased risk of Behçet's disease, Graves' disease, kidney stone disease, fracture of radium/ulna, basal cell carcinoma, and overall cataracts. Stratified analyses showed that the inverse association between genetically predisposed 25(OH)D concentrations and multiple sclerosis risk was significant and consistent regardless of the genetic instruments GIs selected. However, the associations with most of the other outcomes were only pronounced when using genetic variants not limited to those in the vitamin D pathway as GIs. The methodological quality of the included MR studies was substantially heterogeneous. Current evidence from linear MR studies strongly supports a causal role of vitamin D in the development of multiple sclerosis. Suggestive support for a number of other health conditions could help prioritize conditions where vitamin D may be beneficial or harmful.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"467-490"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424554","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":"Towards more reliable non-linear mendelian randomization investigations.","authors":"Stephen Burgess","doi":"10.1007/s10654-024-01121-9","DOIUrl":"10.1007/s10654-024-01121-9","url":null,"abstract":"","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"447-449"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multidisciplinary and structured investigation of three suspected clusters of transverse upper limb reduction defects in France","authors":"Julie Boudet-Berquier, Christophe Demattei, Laurence Guldner, Anne Gallay, Sylvie Manouvrier, Jérémie Botton, Claire Philippat, Fleur Delva, Juliette Bloch, Caroline Semaille, Sylvie Odent, Isabelle Perthus, Hanitra Randrianaivo, Sylvie Babajko, Tiphaine Barjat, Claire Beneteau, Naima Brennetot, Ester Garne, Georges Haddad, Mounia Hocine, Isabelle Lacroix, Klervi Leuraud, Michel Mench, Joan Morris, Sophie Patrier, Arnaud Sartelet, Alain Verloes, Christophe Bonaldi, Mélina Le Barbier, Bertrand Gagnière, Philippe Pépin, Ronan Ollivier, Monique Bitoun, Lisa King, Andrea Guajardo-Villar, Eugenia Gomes, Jean-Claude Desenclos, Nolwenn Regnault, Alexandra Benachi","doi":"10.1007/s10654-024-01125-5","DOIUrl":"https://doi.org/10.1007/s10654-024-01125-5","url":null,"abstract":"<p><b>Introduction</b>: Between 2019–2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France<i>,</i> where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas. <b>Methods: </b>The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases’ homes concerning their plant product use. <b>Results: </b>After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed. <b>Discussion: </b>Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"22 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140807369","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}