medRxiv最新文献

{"title":"Transparency in the secondary use of health data: Assessing the status quo of guidance and best practices","authors":"O. R. van den Akker, R. T. Thibault, J. Ioannidis, S. G. Schorr, D. Strech","doi":"10.1101/2024.08.11.24311808","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311808","url":null,"abstract":"We evaluated what guidance exists in the literature to improve the transparency of studies that make secondary use of health data. To find relevant literature, we searched PubMed and Google Scholar and drafted a list of health organizations based on our personal expertise. We quantitatively and qualitatively coded different types of research transparency: registration, methods reporting, results reporting, data sharing, and code sharing. We found 54 documents that provide recommendations to improve the transparency of studies making secondary use of health data, mainly in relation to study registration (n = 27) and methods reporting (n = 39). Only three documents made recommendations on data sharing or code sharing. Recommendations for study registration and methods reporting mainly came in the form of structured documents like registration templates and reporting guidelines. Aside from the recommendations aimed directly at researchers, we found 31 recommendations aimed at the wider research community, typically on how to improve research infrastructure. Limitations or challenges of improving transparency were rarely mentioned, highlighting the need for more nuance in providing transparency guidance for studies that make secondary use of health data.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the molecular basis of the genetic correlation between body mass index and brain morphological traits","authors":"D. Fusco, C. Marinelli, M. Andre, L. Troiani, M. Noe, F. Pizzagalli, D. Marnetto, P. Provero","doi":"10.1101/2024.08.09.24311778","DOIUrl":"https://doi.org/10.1101/2024.08.09.24311778","url":null,"abstract":"Several studies have demonstrated significant phenotypic and genetic correlations between body mass index (BMI) and brain morphological traits derived from structural magnetic resonance imaging (sMRI). We use the sMRI, BMI, and genetic data collected by the UK Biobank to systematically compute the genetic correlations between area, volume, and thickness measurements of hundreds of brain structures on one hand, and BMI on the other. In agreement with previous literature, we find many such measurements to have negative genetic correlation with BMI. We then dissect the molecular mechanisms underlying such correlations using brain eQTL data and summary-based Mendelian randomization, thus producing an atlas of genes whose genetically regulated expression in brain tissues pleiotropically affects brain morphology and BMI. Fine-mapping followed by colocalization analysis allows, in several cases, the identification of credible sets of variants likely to be causal for both the macroscopic phenotypes and for gene expression. In particular, epigenetic fine mapping identifies variant rs7187776 in the 5' UTR of the TUFM gene as likely to be causal of increased BMI and decreased caudate volume, possibly through the creation, by the alternate allele, of an ETS binding site leading to increased chromatin accessibility, specifically in microglial cells.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"17 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAJOR AETIOLOGIES OF MALE INFERTILITY AMONG COUPLES ATTENDING FERTILITY CLINICS IN OSUN STATE, NIGERIA: FINDINGS FROM A MIXED METHOD STUDY","authors":"Kehinde Awodele, Sunday Charles Adeyemo, Eniola Dorcas, Olabode, A. Fasanu, Akintunde Rasaq Akindele, O. Adegboyega, Abidemi Olagunju, Olusegun Oyerinde, Lanre Olaitan","doi":"10.1101/2024.08.10.24311725","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311725","url":null,"abstract":"Male infertility accounts for nearly half of the infertility cases globally. Seminal fluid analysis (SFA) is a critical diagnostic tool in the evaluation of male infertility. This study aimed to assess the implications of seminal fluid analysis on male infertility among patients attending fertility clinics in Osogbo, Nigeria. The study employed mixed-method approach of both qualitative (Key informant interview) among 10 participants and quantitative method (cross-sectional survey) using pre-tested structured questionnaire among 305 respondents. The respondents in the cross-sectional survey were also made to undergo seminal fluid analysis. The data from the qualitative study was analysed using Atlas ti while data from the quantitative study were analysed using IBM Statistical Product for Service Solution (SPSS) version 27. 0. Descriptive statistics was carried out for all variables. The univariate, bivariate and multivariate analysis were done using p<0.05 as level of significance. The seminal fluid analysis of the respondents revealed that 241 (79.0%) had Normal sperm count (>32 million per ejaculation) while 64 (21.0%) had abnormal sperm count. Only 101 (33.1%) had normal progressive motility (>32 percent) while 204 (66.9%) had abnormal (Athenospermia) progressive motility. 195 (63.9%) were found to have abnormal morphology (Teratospermia i.e., <4%). The qualitative analysis further analysed the implications of SFA parameters on infertile males and these were substantial, extending beyond physical health to encompass psychological, emotional, and social well-being. The study concluded that lifestyle modifications and early diagnosis as well as prompt treatment of medical conditions can curb high prevalence abnormality of SFA, hence reduce male infertility in our environment. The study recommends that advocacy program, early screening and public health education will further reduce the burden of infertility among the female folks.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"15 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association studies found CCDC7 and ITGB1 associated with diabetic retinopathy","authors":"T. Cai, Q. Pan, Y. Tao, L. Yang, C. Nangia, A. Rajendrakumar, Y. Huang, Y. Shao, Y. Ye, T. Dottorini, M. Haque, C. N. Palmer, W. Meng","doi":"10.1101/2024.08.10.24311791","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311791","url":null,"abstract":"Purpose: Diabetic retinopathy (DR), a complication affecting the eyes, is associated with diabetes. This study aims to identify genetic variants associated with DR in patients with type 1 diabetes in the UK Biobank cohort (n = 1,004). Methods: A genome-wide association study (GWAS) was conducted to identify significant genetic variants of DR in type 1 diabetes. The findings are set to undergo validation during the replication and meta-analysis stages by using six cohorts: African American, European, FinnGen, GoSHARE, GoDARTS and Caucasian Australians. Results: In a locus, top single nucleotide polymorphism (SNP) rs184619214 in CCDC7 reached a GWAS significance level (p = 6.38 x 10-9) and rs79853754 in ITGB1 (p = 3.24 x 10-8), with both genes being adjacent to each other. The SNP-based heritability was estimated to be 31.09%. Rs184619214 was replicated and reached statistical significance (p < 5.0 x 10-8) in the meta-analysis stage. Pathway analysis revealed that ITGB1 is involved in the generation of biomolecules that impact the progression of DR. PheWAS analysis revealed that osteoarthritis (OA) of the hip was significantly associated with most of the SNPs of the locus. Mendelian Randomization further confirmed an association between OA and DR. Conclusions: Our study has identified a novel genomic risk locus associated with DR in type 1 diabetes, located in the intergenic region between the CCDC7 and ITGB1 genes, providing insights for DR researchers. Keywords: Diabetic retinopathy; genome-wide association study; meta-analysis; Phenome-Wide Association Study; type 1 diabetes","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"1 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the molecular basis of the genetic correlation between body mass index and brain morphological traits","authors":"D. Fusco, C. Marinelli, M. Andre, L. Troiani, M. Noe, F. Pizzagalli, D. Marnetto, P. Provero","doi":"10.1101/2024.08.09.24311778","DOIUrl":"https://doi.org/10.1101/2024.08.09.24311778","url":null,"abstract":"Several studies have demonstrated significant phenotypic and genetic correlations between body mass index (BMI) and brain morphological traits derived from structural magnetic resonance imaging (sMRI). We use the sMRI, BMI, and genetic data collected by the UK Biobank to systematically compute the genetic correlations between area, volume, and thickness measurements of hundreds of brain structures on one hand, and BMI on the other. In agreement with previous literature, we find many such measurements to have negative genetic correlation with BMI. We then dissect the molecular mechanisms underlying such correlations using brain eQTL data and summary-based Mendelian randomization, thus producing an atlas of genes whose genetically regulated expression in brain tissues pleiotropically affects brain morphology and BMI. Fine-mapping followed by colocalization analysis allows, in several cases, the identification of credible sets of variants likely to be causal for both the macroscopic phenotypes and for gene expression. In particular, epigenetic fine mapping identifies variant rs7187776 in the 5' UTR of the TUFM gene as likely to be causal of increased BMI and decreased caudate volume, possibly through the creation, by the alternate allele, of an ETS binding site leading to increased chromatin accessibility, specifically in microglial cells.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141920043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy, public health impact and optimal use of the Takeda dengue vaccine","authors":"B. Cracknell Daniels, N. M. Ferguson, I. Dorigatti","doi":"10.1101/2024.08.10.24311393","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311393","url":null,"abstract":"Dengue is the most common arboviral infection, causing substantial morbidity and mortality globally. The licensing of Qdenga, a second-generation vaccine developed by Takeda Pharmaceuticals, is therefore timely, but the potential public health impact of vaccination across transmission settings needs to be evaluated. To address this, we characterised Qdenga's efficacy profile using mathematical models calibrated to published clinical trial data and estimated the public health impact of routine vaccine use. We find that efficacy depends on the infecting serotype, serological status, and age. We estimate that vaccination of children aged over six years in moderate to high dengue transmission settings (seroprevalence at 9 years of age > 60%) could reduce the burden of hospitalised dengue by 10-22% on average over ten years. We find some evidence of a risk of vaccine-induced disease enhancement in seronegative vaccine recipients for dengue serotypes 3 and 4, especially for children under six years of age. Because of this, the benefits of vaccination in lower transmission settings are more uncertain, and more data on the long-term efficacy of Qdenga against serotypes 3 and 4 are needed.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"15 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning to Predict-Then-Optimize Elective Orthopaedic Surgery Scheduling Improves Operating Room Utilization","authors":"MASc Johnathan R. Lex MBChB, Jacob Mosseri BASc MASc, Mba Frcsc Jay Toor MD, Aazad Abbas HBSc, Michael Simone BASc, Bheeshma Ravi, Cari M. Whyne, Elias B. Khalil","doi":"10.1101/2024.08.10.24311370","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311370","url":null,"abstract":"Objective: To determine the potential for improving elective surgery scheduling for total knee and hip arthroplasty (TKA and THA, respectively) by utilizing a two-stage approach that incorporates machine learning (ML) prediction of the duration of surgery (DOS) with scheduling optimization. Materials and Methods: Two ML models (for TKA and THA) were trained to predict DOS using patient factors based on 302,490 and 196,942 examples, respectively, from a large international database. Three optimization formulations based on varying surgeon flexibility were compared: Any- surgeons could operate in any operating room at any time, Split- limitation of two surgeons per operating room per day, and MSSP- limit of one surgeon per operating room per day. Two years of daily scheduling simulations were performed for each optimization problem using ML-prediction or mean DOS over a range of schedule parameters. Constraints and resources were based on a high volume arthroplasty hospital in Canada. Results: The Any scheduling formulation performed significantly worse than the Split and MSSP formulations with respect to overtime and underutilization (p<0.001). The latter two problems performed similarly (p>0.05) over most schedule parameters. The ML-prediction schedules outperformed those generated using a mean DOS over all schedule parameters, with overtime reduced on average by 300 to 500 minutes per week. Using a 15-minute schedule granularity with a wait list pool of minimum 1 month generated the best schedules. Conclusion: Assuming a full waiting list, optimizing an individual surgeons elective operating room time using an ML-assisted predict-then optimize scheduling system improves overall operating room efficiency, significantly decreasing overtime.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"18 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new preprocedural predictive risk model for post-endoscopic retrograde cholangiopancreatography pancreatitis: The SuPER model","authors":"M. Sugimoto, T. Takagi, T. Suzuki, H. Shimizu, G. Shibukawa, Y. Nakajima, Y. Takeda, Y. Noguchi, R. Kobayashi, H. Imamura, H. Asama, N. Konno, Y. Waragai, H. Akatsuka, R. Suzuki, T. Hikichi, H. Ohira","doi":"10.1101/2024.08.11.24311807","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311807","url":null,"abstract":"Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a severe and deadly adverse event following ERCP. The ideal method for predicting PEP risk before ERCP has yet to be identified. We aimed to establish a simple PEP risk score model (SuPER model: Support for PEP Reduction) that can be applied before ERCP.\u0000\u0000Methods: This multicenter study enrolled 2074 patients who underwent ERCP. Among them, 1037 patients each were randomly assigned to the development and validation cohorts. In the development cohort, the risk score model for predicting PEP was established by logistic regression analysis. In the validation cohort, the performance of the model was assessed.\u0000\u0000Results: In the development cohort, five PEP risk factors that could be identified before ERCP were extracted and assigned weights according to their respective regression coefficients: -2 points for pancreatic calcification, 1 point for female sex, and 2 points for intraductal papillary mucinous neoplasm, a native papilla of Vater, or the use of pancreatic duct procedures. The PEP occurrence rate was 0% among low-risk patients ([≤] 0 points), 5.5% among moderate-risk patients (1 to 3 points), and 20.2% among high-risk patients (4 to 7 points). In the validation cohort, the C-statistic of the risk score model was 0.71 (95% CI 0.64-0.78), which was considered acceptable. The PEP risk classification (low, moderate, and high) was a significant predictive factor for PEP that was independent from intraprocedural PEP risk factors (precut sphincterotomy and inadvertent pancreatic duct cannulation) (OR 4.2, 95% CI 2.8-6.3, P < 0.01).\u0000\u0000Conclusions: The PEP risk score allows an estimation of the risk of PEP prior to ERCP, regardless of whether the patient has undergone pancreatic duct procedures. This simple risk model, consisting of only five items, may aid in predicting and explaining the risk of PEP before ERCP and in preventing PEP by allowing selection of the appropriate expert endoscopist and useful PEP prophylaxes.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"3 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant rituximab and elevated intratumoural CD8 expression are associated with sustained disease control after radiotherapy in early-stage follicular lymphoma: TROG99.03","authors":"Michael P. MacManus MBBChBAO, J. F. S. Mbbs, H. Tsang, Richard Fisher, Colm Keane MBBChBAO, Muhammed B Sabdia BSc, S. Law, J. Gunawardana, Karthik Nath Mbbs, Stephen H Kazakoff, Mario L. Marques-Piubelli, Daniela E Duenas, Michael R. Green, Daniel Roos, Peter O’Brien Mbbs, Andrew McCann MBChB, Richard Tsang, Sidney Davis, David Christie MBChB, Chan Cheah Mbbs, B. Amanuel, Tara Cochrane Mbbs, Jason Butler Mbbs, Anna Johnston Mbbs, M. Shanavas, Li Li, Claire Vajdic, R. Kridel, Victoria Shelton BSc, Samantha Hershenfield BSc, Tara Baetz, David Lebrun, Nathalie Johnson, M. Brodtkorb, Maja Ludvigsen, Francesco d'Amore, Ella R Thompson, Piers Blombery Mbbs, Maher K Gandhi MBChB, WD Joshua, Tobin Mbbs, Michael MacManus, M. Gandhi, J. Tobin, Luisa Solis, Mei Jiang, Beatriz Sanchez-Espiridion, Wei Lu, Khaja B. Khan, Jianling Zhou","doi":"10.1101/2024.08.09.24311704","DOIUrl":"https://doi.org/10.1101/2024.08.09.24311704","url":null,"abstract":"Background: We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies. Methods: Patients with ESFL were randomised to involved-field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT+CVP). From 2006 rituximab was added to IFRT+CVP (IFRT+R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively). Findings: Between 2000-2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. Per protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR]=0.60, 95%CI=0.37-0.98, p=0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR=0.44, 95%CI=0.16-1.18, p=0.11, 10-year OS 95% vs 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p=0.045). PFS of IFRT+R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT+CVP) was superior (HR=0.36, 95%CI=0.13-0.82, p=0.013). Amongst PET-staged patients, PFS differences between IFRT+R-CVP vs. IFRT were maintained (HR=0.38, 95%CI=0.16-0.89, p=0.027) indicating benefit distinct from stage migration. FL-related mutations and BCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR=0.45, 95%CI=0.26-0.79, p=0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p=0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p=0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease. Interpretation: Adjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL. Funding: Cancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"2 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141920047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiotoxicity in Pediatric Cancer Survivorship: Patterns, Predictors, and Implications for Long-term Care","authors":"Masab A. Mansoor, Dba","doi":"10.1101/2024.08.10.24311795","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311795","url":null,"abstract":"Background Improved survival rates in pediatric cancer have shifted focus to long-term effects of treatment, with cardiovascular complications emerging as a leading cause of morbidity and mortality. Understanding the patterns and predictors of cardiotoxicity is crucial for risk stratification, treatment optimization, and long-term care planning. Objective This study aimed to investigate the prevalence, incidence, and risk factors of cardiotoxicity in pediatric cancer survivors using data from the Childhood Cancer Survivor Study (CCSS). Methods We conducted a retrospective cohort study of 24,938 five-year survivors of childhood cancer diagnosed between 1970 and 1999. Cardiovascular complications, including cardiomyopathy, coronary artery disease, valvular heart disease, and arrhythmias, were assessed through self-reported questionnaires and medical record review. Cox proportional hazards models were used to evaluate risk factors, and a prediction model was developed using multivariable logistic regression. Results The cumulative incidence of any cardiovascular complication by 30 years post-diagnosis was 18.7% (95% CI: 17.9%-19.5%). Significant risk factors included anthracycline exposure (HR 2.31, 95% CI: 2.09-2.55 for doses [≥] 250 mg/m), chest radiation (HR 1.84, 95% CI: 1.66-2.05 for doses [≥] 20 Gy), older age at diagnosis, male sex, and obesity. A risk prediction model demonstrated good discrimination (C-statistic: 0.78, 95% CI: 0.76-0.80). Survivors had a significantly higher risk of cardiovascular complications compared to sibling controls (OR 3.7, 95% CI: 3.2-4.2). Conclusions Childhood cancer survivors face a substantial and persistent risk of cardiovascular complications. The identified risk factors and prediction model can guide personalized follow-up strategies and interventions. These findings underscore the need for lifelong cardiovascular monitoring and care in this population.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"15 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}