{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T18:40:53Z","timestamp":1762800053974,"version":"build-2065373602"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>This retrospective open cohort study develops and externally validates a clinical prediction model (CPM) to predict the joint risk of two important outcomes occurring within the next year in people with epilepsy (PWE). These are: A) seizure-related emergency department or hospital admission; and B) epilepsy-related death. This will provide clinicians with a tool to predict either or both of these common outcomes. This has not previously been done despite both being potentially avoidable, interrelated, and devastating for patients and their families. We hypothesise that the CPM will identify individuals at high or low risk of either or both outcomes. We will guide clinicians on proposed actions to take based on the overall risk score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Routinely collected, anonymised, electronic health data from the following research platforms will be used: i) Clinical Practice Research Datalink (CPRD); ii) Secure Anonymised Information Linkage databank (SAIL); iii) Combined Intelligence for Population Health Action (CIPHA); and iv) TriNetX. We will study PWE aged \u226516 years having outcomes A and\/or B between 2010\u20132024 within these datasets. Sample sizes of over 100,000 PWE are expected across these datasets. Candidate predictors will include demographic, lifestyle, clinical, and management variables. Logistic regression and multistate modelling will be used to develop a suitable CPM. The choice of modelling approach will be informed by consultation with clinicians and members of the public. We will assess the model\u2019s predictive performance using CPRD as a development dataset, and conduct external validation using SAIL, CIPHA, and TriNetX.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This large study will develop and validate a CPM for PWE, creating an internationally generalisable tool for subsequent clinical implementation. It will predict the joint risk of acute admission and death in PWE. Mortality prediction is highlighted by NICE as a key recommendation for epilepsy research. The study has been co-developed by epilepsy researchers and members of the public affected by epilepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0328809","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T18:30:17Z","timestamp":1762799417000},"page":"e0328809","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Developing and validating a clinical prediction model to predict epilepsy-related emergency department attendance, hospital admission, or death: A cohort study protocol"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9588-2944","authenticated-orcid":true,"given":"Gashirai K.","family":"Mbizvo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glen P.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-9212","authenticated-orcid":true,"given":"Laura J.","family":"Bonnett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieta","family":"Schofield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilary","family":"Garret","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Griffiths","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W Owen","family":"Pickrell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3392-1650","authenticated-orcid":true,"given":"Iain","family":"Buchan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory Y.H.","family":"Lip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony G.","family":"Marson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"issue":"3","key":"pone.0328809.ref001","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2014-007325","article-title":"National Audit of Seizure management in Hospitals (NASH): results of the national audit of adult epilepsy in the UK","volume":"5","author":"PA Dixon","year":"2015","journal-title":"BMJ Open"},{"issue":"10","key":"pone.0328809.ref002","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-023352","article-title":"Emergency hospital care for adults with suspected seizures in the NHS in England 2007-2013: a cross-sectional study","volume":"8","author":"JM Dickson","year":"2018","journal-title":"BMJ Open"},{"issue":"10","key":"pone.0328809.ref003","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2021-052841","article-title":"Epilepsy and mortality: a retrospective cohort analysis with a nested case-control study identifying causes and risk factors from primary care and linkage-derived data","volume":"11","author":"G Wojewodka","year":"2021","journal-title":"BMJ Open"},{"issue":"6","key":"pone.0328809.ref004","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1093\/brain\/awac463","article-title":"Case-control study developing Scottish Epilepsy Deaths Study Score to predict epilepsy-related death","volume":"146","author":"GK Mbizvo","year":"2023","journal-title":"Brain"},{"issue":"11","key":"pone.0328809.ref005","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1111\/epi.17065","article-title":"A national study of epilepsy-related deaths in Scotland: Trends, mechanisms, and avoidable deaths","volume":"62","author":"GK Mbizvo","year":"2021","journal-title":"Epilepsia"},{"issue":"01","key":"pone.0328809.ref006","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1017\/S1463423609990211","article-title":"Prioritizing ambulatory care sensitive hospital admissions in England for research and intervention: a Delphi exercise","volume":"11","author":"S Purdy","year":"2009","journal-title":"Primary Health Care"},{"issue":"8","key":"pone.0328809.ref007","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2013-003482","article-title":"Predicting risk of emergency admission to hospital using primary care data: derivation and validation of QAdmissions score","volume":"3","author":"J Hippisley-Cox","year":"2013","journal-title":"BMJ Open"},{"issue":"11","key":"pone.0328809.ref008","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2019-031696","article-title":"Developing patient-centred, feasible alternative care for adult emergency department users with epilepsy: protocol for the mixed-methods observational \u201cCollaborate\u201d project","volume":"9","author":"AJ Noble","year":"2019","journal-title":"BMJ Open"},{"key":"pone.0328809.ref009","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.seizure.2020.02.012","article-title":"Clinically unnecessary and avoidable emergency health service use for epilepsy: A survey of what English services are doing to reduce it","volume":"76","author":"A Mathieson","year":"2020","journal-title":"Seizure"},{"key":"pone.0328809.ref010","doi-asserted-by":"crossref","first-page":"106192","DOI":"10.1016\/j.eplepsyres.2019.106192","article-title":"Epilepsy-related and other causes of mortality in people with epilepsy: A systematic review of systematic reviews","volume":"157","author":"GK Mbizvo","year":"2019","journal-title":"Epilepsy Res"},{"issue":"8","key":"pone.0328809.ref011","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1212\/WNL.0000000000002253","article-title":"Recognizing and preventing epilepsy-related mortality: A call for action","volume":"86","author":"O Devinsky","year":"2016","journal-title":"Neurology"},{"key":"pone.0328809.ref012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.seizure.2021.11.003","article-title":"Increasing epilepsy-related mortality: A multiple causes of death study in Northern Italy","volume":"94","author":"V Casotto","year":"2022","journal-title":"Seizure"},{"key":"pone.0328809.ref013","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.seizure.2021.11.017","article-title":"Epilepsy mortality in Wales during COVID-19","volume":"94","author":"H Daniels","year":"2022","journal-title":"Seizure"},{"key":"pone.0328809.ref014","unstructured":"Chief Medical Officer. Guidance for Doctors Completing Medical Certificates of The Cause of Death (MCCD) and its Quality Assurance 2018 03\/03\/2020. Available from: https:\/\/bit.ly\/2yyMzlC"},{"issue":"3","key":"pone.0328809.ref015","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000013068","article-title":"Epilepsy-Related Mortality in Children and Young Adults in Denmark: A Nationwide Cohort Study","volume":"98","author":"M Kl\u00f8vgaard","year":"2022","journal-title":"Neurology"},{"issue":"2","key":"pone.0328809.ref016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001381","article-title":"Prognosis Research Strategy (PROGRESS) 3: prognostic model research","volume":"10","author":"EW Steyerberg","year":"2013","journal-title":"PLoS Med"},{"key":"pone.0328809.ref017","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.seizure.2021.11.007","article-title":"Risk of seizure recurrence in people with single seizures and early epilepsy - Model development and external validation","volume":"94","author":"LJ Bonnett","year":"2022","journal-title":"Seizure"},{"key":"pone.0328809.ref018","article-title":"Guide to presenting clinical prediction models for use in clinical settings","volume":"365","author":"LJ Bonnett","year":"2019","journal-title":"BMJ"},{"issue":"12","key":"pone.0328809.ref019","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1093\/eurheartj\/ehr488","article-title":"Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study","volume":"33","author":"L Friberg","year":"2012","journal-title":"Eur Heart J"},{"issue":"2","key":"pone.0328809.ref020","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1378\/chest.09-1584","article-title":"Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation","volume":"137","author":"GYH Lip","year":"2010","journal-title":"Chest"},{"key":"pone.0328809.ref021","unstructured":"NICE. Atrial fibrillation: diagnosis and management NICE guideline [NG196]. 2021."},{"key":"pone.0328809.ref022","unstructured":"Levy ML, Andrews R, Buckingham R, Evans H, Francis C, Houston R. Confidential Enquiry report. Why asthma still kills: The National Review of Asthma Deaths (NRAD) 2014 19\/08\/2022. Available from: www.rcplondon.ac.uk\/sites\/default\/files\/why-asthma-still-kills-full-report.pdf"},{"issue":"7","key":"pone.0328809.ref023","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1111\/epi.16928","article-title":"Improving prediction of sudden unexpected death in epilepsy: From SUDEP-7 to SUDEP-3","volume":"62","author":"R Tarighati Rasekhi","year":"2021","journal-title":"Epilepsia"},{"issue":"21","key":"pone.0328809.ref024","article-title":"Sudden Unexpected Death in Epilepsy: A Personalized Prediction Tool","volume":"96","author":"A Jha","year":"2021","journal-title":"Neurology"},{"key":"pone.0328809.ref025","unstructured":"SUDEP Action. SUDEP and Seizure Safety Checklist 2017 [07\/11\/2018]. Available from: https:\/\/bit.ly\/347i8iY"},{"key":"pone.0328809.ref026","unstructured":"National Institute of Health and Care Excellence (NICE). Epilepsies in children, young people and adults: recommendations for research. NICE guideline [NG217] [Internet]. 2022 16\/10\/2023. Available from: https:\/\/tinyurl.com\/mr44t5jf"},{"issue":"2","key":"pone.0328809.ref027","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/sim.8787","article-title":"Clinical prediction models to predict the risk of multiple binary outcomes: a comparison of approaches","volume":"40","author":"GP Martin","year":"2021","journal-title":"Stat Med"},{"key":"pone.0328809.ref028","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.g7594","article-title":"Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement","volume":"350","author":"GS Collins","year":"2015","journal-title":"BMJ"},{"key":"pone.0328809.ref029","unstructured":"CPRD. Latest data from CPRD2021 03\/12\/2022. Available from: https:\/\/cprd.com\/latest-data-cprd-1"},{"key":"pone.0328809.ref030","unstructured":"TriNetX. Welcome to the world\u2019s largest, living ecosystem of real-world data and evidence for the life sciences and healthcare industries. Global data, for global health 2023 25\/08\/2022. Available from: www.trinetx.com"},{"issue":"10","key":"pone.0328809.ref031","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S2215-0366(22)00260-7","article-title":"Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1\u2008284\u2008437 patients","volume":"9","author":"M Taquet","year":"2022","journal-title":"Lancet Psychiatry"},{"key":"pone.0328809.ref032","unstructured":"Buchan I. Civic Data Cooperatives (CDC): Combined Intelligence for Population Health Action (CIPHA). 2021 [cited 19\/10\/2023]. In: Open Life Data Framework [Internet]. [cited 19\/10\/2023]. Available from: https:\/\/tinyurl.com\/3theffer"},{"key":"pone.0328809.ref033","article-title":"Calculating the sample size required for developing a clinical prediction model","volume":"368","author":"RD Riley","year":"2020","journal-title":"BMJ"},{"issue":"7","key":"pone.0328809.ref034","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1111\/epi.16547","article-title":"The accuracy of using administrative healthcare data to identify epilepsy cases: A systematic review of validation studies","volume":"61","author":"GK Mbizvo","year":"2020","journal-title":"Epilepsia"},{"key":"pone.0328809.ref035","doi-asserted-by":"crossref","first-page":"106462","DOI":"10.1016\/j.eplepsyres.2020.106462","article-title":"Validating the accuracy of administrative healthcare data identifying epilepsy in deceased adults: A Scottish data linkage study","volume":"167","author":"GK Mbizvo","year":"2020","journal-title":"Epilepsy Res"},{"issue":"10","key":"pone.0328809.ref036","doi-asserted-by":"crossref","first-page":"101868","DOI":"10.1016\/j.cpcardiol.2023.101868","article-title":"Epilepsy-Heart Syndrome: Incidence and Clinical Outcomes of Cardiac Complications in patients with Epilepsy","volume":"48","author":"T Bucci","year":"2023","journal-title":"Curr Probl Cardiol"},{"issue":"5","key":"pone.0328809.ref037","doi-asserted-by":"crossref","DOI":"10.1503\/cmaj.190757","article-title":"Development and validation of the Cambridge Multimorbidity Score","volume":"192","author":"RA Payne","year":"2020","journal-title":"CMAJ"},{"issue":"9","key":"pone.0328809.ref038","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2024-086589","article-title":"Atrial fibrillation after cardiac surgery: identifying candidate predictors through a Delphi process","volume":"14","author":"J Bedford","year":"2024","journal-title":"BMJ Open"},{"key":"pone.0328809.ref039","article-title":"Multivariable Modeling Strategies. 2015 [cited 18\/08\/2022].","volume-title":"Regression Modeling Strategies [Internet]","author":"FE Harrell","year":"2022"},{"issue":"1","key":"pone.0328809.ref040","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","article-title":"Regression Shrinkage and Selection Via the Lasso","volume":"58","author":"R Tibshirani","year":"1996","journal-title":"Journal of the Royal Statistical Society Series B: Statistical Methodology"},{"issue":"4","key":"pone.0328809.ref041","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/(SICI)1097-0258(19970228)16:4<385::AID-SIM380>3.0.CO;2-3","article-title":"The lasso method for variable selection in the Cox model","volume":"16","author":"R Tibshirani","year":"1997","journal-title":"Stat Med"},{"key":"pone.0328809.ref042","unstructured":"CIPHA. Frequently Asked Questions: Combined Intelligence for Population Health Action (CIPHA): Population Health2020. Available from: https:\/\/bit.ly\/3JlIPWr"},{"key":"pone.0328809.ref043","unstructured":"Cheshire and Merseyside Health and Care Partnership. Combined Intelligence for Population Health Action (CIPHA)2022 25\/08\/2022. Available from: https:\/\/www.cipha.nhs.uk"},{"key":"pone.0328809.ref044","doi-asserted-by":"crossref","first-page":"100107","DOI":"10.1016\/j.lanepe.2021.100107","article-title":"Evaluating social and spatial inequalities of large scale rapid lateral flow SARS-CoV-2 antigen testing in COVID-19 management: An observational study of Liverpool, UK (November 2020 to January 2021)","volume":"6","author":"MA Green","year":"2021","journal-title":"Lancet Reg Health Eur"},{"issue":"1","key":"pone.0328809.ref045","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41512-020-00090-3","article-title":"Continual updating and monitoring of clinical prediction models: time for dynamic prediction systems?","volume":"5","author":"DA Jenkins","year":"2021","journal-title":"Diagn Progn Res"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0328809","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T18:30:25Z","timestamp":1762799425000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0328809"}},"subtitle":[],"editor":[{"given":"Francesco","family":"Deleo","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0328809","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]}}}