{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:14:41Z","timestamp":1788311681952,"version":"build-2803163510"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Roche Diagnostics International Ltd"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Headaches account for up to 4.5% of emergency department visits, where they present a significant diagnostic challenge. While primary headaches are benign, secondary headaches can be life-threatening. It is essential to rapidly differentiate between primary and secondary headaches as the latter require immediate diagnostic work-up. Current assessment relies on subjective measures; time constraints can result in overuse of diagnostic neuroimaging, prolonging diagnosis, and adding to economic burden. There is therefore an unmet need for a time- and cost-efficient, quantitative triaging tool to guide further diagnostic testing. Routine blood tests may provide important diagnostic and prognostic biomarkers indicating underlying headache causes. In this retrospective study (approved by the UK Medicines and Healthcare products Regulatory Agency Independent Scientific Advisory Committee for Clinical Practice Research Datalink (CPRD) research [20_000173]), UK CPRD real-world data from patients (n = 121,241) presenting with headache from 1993\u20132021 were used to generate a predictive model based on a machine learning (ML) approach for primary versus secondary headaches. A ML-based predictive model was constructed using two different methods (logistic regression and random forest) and the following predictors were evaluated: ten standard measurements of complete blood count (CBC) test, 19 ratios of the ten CBC test parameters, and patient demographic and clinical characteristics. The model\u2019s predictive performance was assessed using a set of cross-validated model performance metrics. The final predictive model showed modest predictive accuracy using the random forest method (balanced accuracy: 0.7405). The sensitivity, specificity, false negative rate (incorrect prediction of secondary headache as primary headache), and false positive rate (incorrect prediction of primary headache as secondary headache) were 58%, 90%, 10%, and 42%, respectively. The ML-based prediction model developed could provide a useful time- and cost-effective quantitative clinical tool to facilitate the triaging of patients presenting to the clinic with headache.<\/jats:p>","DOI":"10.1371\/journal.pone.0282237","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T18:31:28Z","timestamp":1678127488000},"page":"e0282237","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["A machine learning approach to support triaging of primary versus secondary headache patients using complete blood count"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7382-8023","authenticated-orcid":true,"given":"Fei","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Torben-Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Magnus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Dejean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"pone.0282237.ref001","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1177\/2049463712459691","article-title":"Headache disorders: differentiating and managing the common subtypes","volume":"6","author":"F. Ahmed","year":"2012","journal-title":"Br J Pain"},{"key":"pone.0282237.ref002","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s10194-005-0210-1","article-title":"Primary headache in emergency department: prevalence, clinical features and therapeutical approach","volume":"6","author":"R Cerbo","year":"2005","journal-title":"J Headache Pain"},{"key":"pone.0282237.ref003","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s10194-019-1053-5","article-title":"Headaches in the emergency department\u2014a survey of patients\u2019 characteristics, facts and needs","volume":"20","author":"A Doretti","year":"2019","journal-title":"J Headache Pain"},{"key":"pone.0282237.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0733-8619(05)70240-1","article-title":"Diagnostic testing for the evaluation of headaches","volume":"14","author":"RW Evans","year":"1996","journal-title":"Neurol Clin"},{"key":"pone.0282237.ref005","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.annemergmed.2008.07.001","article-title":"Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with acute headache","volume":"52","author":"JA Edlow","year":"2008","journal-title":"Ann Emerg Med"},{"key":"pone.0282237.ref006","doi-asserted-by":"crossref","first-page":"e532","DOI":"10.3399\/bjgp14X681325","article-title":"Diagnosing headache in primary care: a qualitative study of GPs\u2019 approaches.","volume":"64","author":"S B\u00f6sner","year":"2014","journal-title":"Br J Gen Pract."},{"key":"pone.0282237.ref007","doi-asserted-by":"crossref","first-page":"e0208728","DOI":"10.1371\/journal.pone.0208728","article-title":"Headache at the emergency room: etiologies, diagnostic usefulness of the ICHD 3 criteria, red and green flags.","volume":"14","author":"J Munoz-Ceron","year":"2019","journal-title":"PLoS One."},{"key":"pone.0282237.ref008","doi-asserted-by":"crossref","first-page":"144","DOI":"10.52964\/AMJA.0563","article-title":"Presentations to an acute medical unit due to headache: a review of 306 consecutive cases.","volume":"11","author":"J Knox","year":"2012","journal-title":"Acute Med."},{"key":"pone.0282237.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"The international classification of headache disorders, 3rd edition.","volume":"38","author":"International Headache Society","year":"2018","journal-title":"Cephalagia"},{"key":"pone.0282237.ref010","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3399\/bjgp08X319440","article-title":"The Headache Innovation Evaluation Group. A new GP with special interest headache service: observational study.","volume":"58","author":"L Ridsdale","year":"2008","journal-title":"Br J Gen Pract"},{"key":"pone.0282237.ref011","unstructured":"British Association for the Study of Headaches (BASH): Headache centres. Available from: https:\/\/www.bash.org.uk\/about\/headache-centres\/ [accessed June 2022]."},{"key":"pone.0282237.ref012","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1017\/S0317167100008921","article-title":"Diagnostic accuracy of neurological problems in the emergency department","volume":"35","author":"JJ Moeller","year":"2008","journal-title":"Can J Neurol Sci"},{"key":"pone.0282237.ref013","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1177\/1756285613489765","article-title":"The role of neuroimaging in the diagnosis of headache disorders.","volume":"6","author":"D Holle","year":"2013","journal-title":"Ther Adv Neurol Disord"},{"key":"pone.0282237.ref014","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s11916-011-0189-z","article-title":"Headache in the emergency department","volume":"15","author":"BW Friedman","year":"2011","journal-title":"Curr Pain Headache Rep"},{"key":"pone.0282237.ref015","doi-asserted-by":"crossref","first-page":"103748","DOI":"10.1016\/j.dib.2019.103748","article-title":"Test volume data for 51 most commonly ordered laboratory tests in Calgary, Alberta, Canada.","volume":"23","author":"I Ma","year":"2019","journal-title":"Data Brief"},{"key":"pone.0282237.ref016","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.tjem.2017.07.003","article-title":"The diagnostic value of complete blood count parameters in patients with subarachnoid hemorrhage","volume":"17","author":"TY Kilic","year":"2017","journal-title":"Turk J Emerg Med"},{"key":"pone.0282237.ref017","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.amsu.2016.07.023","article-title":"The change of neutrophils\/lymphocytes ratio in migraine attacks: a case-controlled study.","volume":"10","author":"KU Karabulut","year":"2016","journal-title":"Ann Med Surg"},{"key":"pone.0282237.ref018","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.ajem.2017.03.063","article-title":"The diagnostic value of the neutrophil-lymphocyte ratio in distinguishing between subarachnoid hemorrhage and migraine.","volume":"35","author":"U Eryigit","year":"2017","journal-title":"Am J Emerg Med"},{"key":"pone.0282237.ref019","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.3171\/jns.2003.98.6.1222","article-title":"Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage","volume":"98","author":"MJ McGirt","year":"2003","journal-title":"J Neurosurg"},{"key":"pone.0282237.ref020","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/0090-3019(84)90330-6","article-title":"Leukocytosis and subarachnoid hemorrhage.","volume":"21","author":"D Parkinson","year":"1984","journal-title":"Surg Neurol."},{"key":"pone.0282237.ref021","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1177\/1076029612453196","article-title":"The prognostic value of an increased mean platelet volume and platelet distribution width in the early phase of cerebral venous sinus thrombosis.","volume":"19","author":"O Kamisli","year":"2013","journal-title":"Clin Appl Thromb Hemost"},{"key":"pone.0282237.ref022","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/ije\/dyv098","article-title":"Data resource profile: Clinical Practice Research Datalink (CPRD).","volume":"44","author":"E Herrett","year":"2015","journal-title":"Int J Epidemiol."},{"key":"pone.0282237.ref023","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1093\/ije\/dyz034","article-title":"Data resource profile: Clinical Practice Research Datalink (CPRD) aurum.","volume":"48","author":"A Wolf","year":"2019","journal-title":"Int J Epidemiol."},{"key":"pone.0282237.ref024","article-title":"Clinical Practice Research Datalink","author":"Medicines & Healthcare products Regulatory Agency","year":"2022","journal-title":"National Institute for Health and Care Research"},{"key":"pone.0282237.ref025","article-title":"A machine learning approach to classify types of headache from laboratory blood test results","author":"Medicines & Healthcare products Regulatory Agency","year":"2021","journal-title":"National Institute for Health and Care Research"},{"key":"pone.0282237.ref026","article-title":"Scalable robust estimators with high breakdown point: package \u2019rrcov\u2019","author":"The Comprehensive R Archive Network","year":"2022"},{"key":"pone.0282237.ref027","doi-asserted-by":"crossref","DOI":"10.1109\/ICACA.2016.7887916","article-title":"LASSO: a feature selection technique in predictive modeling for machine learning.","volume":"24","author":"R Muthukrishnan","year":"2016","journal-title":"IEEE International Conference on Advances in Computer Applications (ICACA);"},{"key":"pone.0282237.ref028","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1023\/A:1012487302797","article-title":"Gene selection for cancer classification using support vector machines.","volume":"46","author":"I Guyon","year":"2002","journal-title":"Machine Learning"},{"key":"pone.0282237.ref029","author":"R Core Team","year":"2022","journal-title":"The R Project for Statistical Computing (version 4.1.3)"},{"key":"pone.0282237.ref030","first-page":"2825","article-title":"Scikit-learn: machine learning in Python.","volume":"12","author":"F Pedregosa","year":"2011","journal-title":"J Mach Learn Res"},{"key":"pone.0282237.ref031","article-title":"API design for machine learning software: experiences from the scikit-learn project","author":"L Buitinck","year":"2013","journal-title":"European Conference on Machine Learning and Principles and Practices of Knowledge Discovery in Databases; September 23\u201327; Prague, Czech Republic"},{"key":"pone.0282237.ref032","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: a 2D graphics environment","volume":"9","author":"JD Hunter","year":"2007","journal-title":"Comput Sci Eng"},{"key":"pone.0282237.ref033","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1001\/jamainternmed.2014.173","article-title":"Headaches and neuroimaging: hHigh utilization and costs despite guidelines","volume":"174","author":"BC Callaghan","year":"2014","journal-title":"JAMA Intern Med"},{"key":"pone.0282237.ref034","doi-asserted-by":"crossref","first-page":"203","DOI":"10.5811\/westjem.2019.1.37352","article-title":"Approach to the diagnosis and management of subarachnoid hemorrhage.","volume":"20","author":"E Marcolini","year":"2019","journal-title":"West J Emerg Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282237","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T18:32:04Z","timestamp":1678127524000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282237"}},"subtitle":[],"editor":[{"given":"Jacopo","family":"Sabbatinelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,3,6]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0282237","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,6]]}}}