{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:59:13Z","timestamp":1787313553033,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG5063A4\/1\/RFA\u20102103\u201037392"],"award-info":[{"award-number":["RG5063A4\/1\/RFA\u20102103\u201037392"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000261","name":"Multiple Sclerosis Society of Canada","doi-asserted-by":"publisher","award":["EGID:P002\/903124"],"award-info":[{"award-number":["EGID:P002\/903124"]}],"id":[{"id":"10.13039\/501100000261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Elevated healthcare use before multiple sclerosis (MS) onset suggests earlier opportunity to identify MS. Yet their timing and sociodemographic effects are unclear. We examined rates of healthcare use (and by age\/sex) for &gt;two decades pre\u2010MS onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified people with MS (PwMS) using administrative data from Canada (Ontario) and Sweden (1991\u20132020) (\u201cadministrative\u201d cohort), and the Swedish MS Registry (\u201cclinical\u201d cohort). The first MS\/demyelinating diagnostic code (administrative) or symptom onset (clinical) defined MS onset. We compared annual rates of healthcare use (hospital, physician, and emergency\u2010room [ED]) pre\u2010onset between PwMS and up to five matched population controls using negative binomial regression, and by age\/sex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The administrative cohort\u2009=\u200935,018\/136,007 PwMS\/controls (Ontario), and 10,269\/51,297 (Sweden). Rates of healthcare use were higher for PwMS than controls up to 28 (of 29) years (Ontario) and up to 15 (of 19) years (Sweden) pre\u2010onset. Annual healthcare use rose steadily as onset approached, particularly escalating 7\u2009years pre\u2010onset in Ontario (e.g., hospital visit rate ratios [RRs] exceeded 1.30), and 6\u2009years in Sweden (physician visit RRs &gt;\u20091.10). RRs peaked the year pre\u2010onset (ED visits [Ontario]\u2009=\u20093.04; 95% CI: 2.94\u20133.13, physician visits [Sweden]\u2009=\u20092.51; 95% CI: 2.44\u20132.59). In the year pre\u2010onset, RRs were disproportionately higher for males (ED RRs [Ontario]\u2009=\u20093.30; 95% CI: 3.13\u20133.48 vs. females\u2009=\u20092.90; 95% CI: 2.79\u20133.02), and dropped steadily by age (physician visit RRs [Sweden]\u2009=\u20092.61\/2.27\/1.97\/1.72 for 50\/40\/30\/20\u2010year\u2010olds). The smaller clinical cohort (7604\/37,974 PwMS\/controls) exhibited similar patterns, albeit more modest, with RRs elevated up to 5\u2009years pre\u2010onset (physician visit RR [year\u20105]\u2009=\u20091.08; 95% CI: 1.02\u20131.14; RR [year\u20101]\u2009=\u20091.39;1.33\u20131.46).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Higher healthcare use was evident decades before MS onset, escalating 6\u20137\u2009years pre\u2010onset, peaking the year before, being disproportionately higher for males and older PwMS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.52267","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T12:42:00Z","timestamp":1738154520000},"page":"415-432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Healthcare use is elevated two decades before a first demyelinating event and differs by age and sex"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-2535","authenticated-orcid":false,"given":"Helen","family":"Tremlett","sequence":"first","affiliation":[{"name":"Faculty of Medicine (Neurology), and the Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (Neurology), and the Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Everett","sequence":"additional","affiliation":[{"name":"ICES  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Asaf","sequence":"additional","affiliation":[{"name":"ICES  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-5762","authenticated-orcid":false,"given":"Ali","family":"Manouchehrinia","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Department of Neurology Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"ICES  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9081-1522","authenticated-orcid":false,"given":"Kyla A.","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Department of Neurology Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Hillert","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Department of Neurology Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinshan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (Neurology), and the Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Maxwell","sequence":"additional","affiliation":[{"name":"ICES  Toronto Ontario Canada"},{"name":"Schools of Pharmacy and Public Health Sciences University of Waterloo  Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth Ann","family":"Marrie","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba  Winnipeg Manitoba Canada"},{"name":"Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba  Winnipeg Manitoba 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