{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:25:38Z","timestamp":1789129538083,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,8]]},"group-title":"Health Informatics","reference-count":23,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["NNF14CC0001"],"award-info":[{"award-number":["NNF14CC0001"]}],"id":[{"id":"https:\/\/ror.org\/04txyc737","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NNF24SA0098829"],"award-info":[{"award-number":["NNF24SA0098829"]}],"id":[{"id":"https:\/\/ror.org\/04txyc737","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>As the use of electronic health records in drug repositioning research increases, so does the need for a well-curated resource describing real-world drug-diagnosis relationships. This need is particularly important in the context of polypharmacy. Although literature-based drug-disease maps exist, they are typically based on mechanistic disease ontologies, which are not widely used in clinical settings and do not align well with the ICD system, which is most often used in healthcare. Here, we used real-world primary and secondary healthcare data from approximately 1.5 million individuals to identify drug-diagnosis co-occurrences ( 736,000 pairs), significant associations (7,763 pairs), and assess direct drug usage through medical expert curation. The final resource comprises 7,763 associations with odds ratios &gt; 3.5, manually annotated by six independent clinicians (3 in the UK and 3 in Denmark). Finally, the clinician annotations were scored using an Expectation-Maximization-based framework providing a confidence score for each pair. Our resource shows that the vast majority of significantly associated drugs and diagnoses in healthcare records are not due to direct treatment of the diagnosis. Additionally, through the annotation results, we demonstrate the importance of accounting for systematic differences among annotators when working with real-world data.<\/jats:p>","DOI":"10.64898\/2026.09.06.26362128","type":"posted-content","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:15:19Z","timestamp":1788930919000},"source":"Crossref","is-referenced-by-count":0,"title":["Real-world drug use in ATC and ICD-10: an expert-curated drug\u2013diagnosis resource based on UK primary care and Danish hospitalization electronic health records"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0647-8892","authenticated-orcid":false,"given":"Ioannis","family":"Louloudis","sequence":"first","affiliation":[{"name":"Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2764-6787","authenticated-orcid":false,"given":"Hannah","family":"Currant","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive, Big Data Institute, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8333-6428","authenticated-orcid":false,"given":"Cai R","family":"Ytsma","sequence":"additional","affiliation":[{"name":"University College London, Institute of Health Informatics, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-5440","authenticated-orcid":false,"given":"Sidsel Christy","family":"Lindgaard","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Oncology, Copenhagen University Hospital \u2013 Herlev and Gentofte, Copen-hagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sedrah Butt","family":"Balaganeshan","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7656-7976","authenticated-orcid":false,"given":"Amalie Dahl","family":"Haue","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"The Heart Center, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5157-5639","authenticated-orcid":false,"given":"Maria","family":"Pisliakova","sequence":"additional","affiliation":[{"name":"University College London Hospitals NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3691-4678","authenticated-orcid":false,"given":"Wentin","family":"Chen","sequence":"additional","affiliation":[{"name":"University College London, Institute of Health Informatics, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0356-9251","authenticated-orcid":false,"given":"Samuel","family":"Thio","sequence":"additional","affiliation":[{"name":"King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0316-5866","authenticated-orcid":false,"given":"S\u00f8ren","family":"Brunak","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9612-7791","authenticated-orcid":false,"given":"Spiros","family":"Denaxas","sequence":"additional","affiliation":[{"name":"University College London, Institute of Health Informatics, London, United Kingdom"},{"name":"British Heart Foundation Data Science Centre, London, United Kingdom"},{"name":"Interdisciplinary Transformation University, Linz, Austria"},{"name":"National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"1067-5027","key":"2026091104202034000_2026.09.06.26362128v1.1","first-page":"546","article-title":"Curating a longitudinal research resource using linked primary care EHR data\u2014a UK Biobank case study. en","volume":"29","year":"2026","journal-title":"Journal of the American Medical Informatics Association"},{"key":"2026091104202034000_2026.09.06.26362128v1.2","first-page":"104507","article-title":"Technological progress in electronic health record system optimization: Systematic review of systematic literature reviews. en","volume":"152","year":"2026","journal-title":"International Journal of Medical Informatics"},{"issue":"1472-6947","key":"2026091104202034000_2026.09.06.26362128v1.3","first-page":"299","article-title":"Evaluating MedDRA-to-ICD terminology mappings. en","volume":"23","year":"2026","journal-title":"BMC Medical Informatics and Decision 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Drug dosage modifications in 24 million in-patient prescriptions covering eight years: A Danish population-wide study of polypharmacy. en. PLOS Digital Health 2 (ed Geisler, B. P.) e0000336. issn: 2767-3170. https:\/\/dx.plos.org\/10.1371\/journal.pdig.0000336 (2026) (Sept. 2023).","DOI":"10.1371\/journal.pdig.0000336"},{"key":"2026091104202034000_2026.09.06.26362128v1.7","first-page":"100570","article-title":"The All of Us Research Program: Data quality, utility, and diversity. en","volume":"3","year":"2026","journal-title":"Patterns"},{"key":"2026091104202034000_2026.09.06.26362128v1.8","unstructured":"Johnson, R. , et al. ClinVec: Unified Embeddings of Clinical Codes Enable Knowledge-Grounded AI in Medicine. en."},{"key":"2026091104202034000_2026.09.06.26362128v1.9","unstructured":"Rodrigues Jean-Marie et al. en. in Studies in Health Technology and Informatics (IOS Press, 2013). https:\/\/www.medra.org\/servlet\/aliasResolver?alias=iospressISSNISBN&issn=0926-9630&volume=192&spage=343 (2026)."},{"key":"2026091104202034000_2026.09.06.26362128v1.10","first-page":"67","article-title":"Building a knowledge graph to enable precision medicine. en","volume":"10","year":"2026","journal-title":"Scientific Data"},{"key":"2026091104202034000_2026.09.06.26362128v1.11","first-page":"D1265","article-title":"DrugBank 6.0: the DrugBank Knowledgebase for 2024. en","volume":"52","year":"2026","journal-title":"Nucleic Acids Research"},{"key":"2026091104202034000_2026.09.06.26362128v1.12","first-page":"D1207","article-title":"The Human Phenotype Ontology in 2021. en","volume":"49","year":"2026","journal-title":"Nucleic Acids Research"},{"key":"2026091104202034000_2026.09.06.26362128v1.13","first-page":"1","article-title":"Using Phecodes for Research with the Electronic Health Record: From PheWAS to PheRS. en","volume":"4","year":"2026","journal-title":"Annual Review of Biomedical Data Science"},{"key":"2026091104202034000_2026.09.06.26362128v1.14","first-page":"954","article-title":"Development and evaluation of an ensemble resource linking medica-tions to their indications. en","volume":"20","year":"2026","journal-title":"Journal of the American Medical Informatics Association"},{"key":"2026091104202034000_2026.09.06.26362128v1.15","doi-asserted-by":"crossref","unstructured":"Henriksen, A. P. , et al. Genome-wide associations spanning 194 in-hospital drug dosage change phenotypes highlight diverse genetic backgrounds in concurrent drug therapy en. 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