{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:44:38Z","timestamp":1781135078778,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evidence suggests signs and symptoms may emerge years before the clinical onset of multiple sclerosis (MS). We investigated secondary healthcare use and medication dispensations before MS onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using linked administrative data, we analyzed a neurologist\u2010diagnosed MS clinical cohort and an algorithm\u2010defined administrative cohort in Sweden (2001\u20132019). People with MS (PwMS) were matched to up to five non\u2010MS comparators by sex, birth year, residency location, and residency duration before the index date (clinical: symptom onset; administrative: first MS\/demyelinating diagnosis code). Annual outpatient visits and hospitalizations by diagnosis codes across 19\u2009years pre\u2010index, and dispensed medications by anatomical and therapeutic classifications across 14\u2009years pre\u2010index were compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The clinical cohort included 7604 PwMS and 37,974 matched comparators (median age at symptom onset\u2009=\u200935.5; 68.5% females). In the 5\u2009years pre\u2010index, outpatient visits were 11%\u201373% higher among PwMS for disturbances of sense organs, nervous, musculoskeletal, digestive, and genitourinary systems, mental health\/behavior, and ill\u2010defined symptoms\/signs, with visits related to sense organs elevated up to 6\u2009years. Hospitalizations were often elevated in the year pre\u2010index. Dispensations of nervous system\u2010related, musculoskeletal, blood\u2010related, metabolic, sensory, respiratory, and dermatological agents were elevated by 6%\u201322% in the 5\u2009years pre\u2010index, with elevations in nervous system\u2010related and musculoskeletal agents extending up to 6\u20139\u2009years pre\u2010index. Findings were similar in the administrative cohort with greater magnitudes and longer durations pre\u2010index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We observed increased hospital, outpatient, and prescription utilization for multiple body systems 6\u20139\u2009years pre\u2010MS onset. These patterns provide a more comprehensive picture of the MS prodrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70464","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T07:36:28Z","timestamp":1765265788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reasons for Healthcare Use Before Onset of Multiple Sclerosis: A Nationwide Matched Cohort Study in Sweden"],"prefix":"10.1111","volume":"32","author":[{"given":"Ali","family":"Manouchehrinia","sequence":"first","affiliation":[{"name":"Karolinska Institutet  Stockholm Sweden"},{"name":"Alberta Health Services  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1924-9378","authenticated-orcid":false,"given":"Yinshan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (Neurology) University of British Columbia and The Djavad Mowafaghian Centre for Brain Health  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (Neurology) University of British Columbia and The Djavad Mowafaghian Centre for Brain Health  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9081-1522","authenticated-orcid":false,"given":"Kyla","family":"McKay","sequence":"additional","affiliation":[{"name":"Karolinska Institutet  Stockholm Sweden"},{"name":"Centre for Molecular Medicine Karolinska Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Maxwell","sequence":"additional","affiliation":[{"name":"ICES  Toronto Ontario Canada"},{"name":"School of Pharmacy University of Waterloo  Waterloo 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