{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:51:20Z","timestamp":1783043480270,"version":"3.54.6"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"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":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate gastrointestinal (GI)\u2010related physician visits and drug dispensations in the 5\u2009years preceding a first recorded demyelinating event or multiple sclerosis (MS) onset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using linked administrative and clinical data from British Columbia (1996\u20132013), Canada, we identified an administrative cohort via a validated algorithm (<jats:italic>n<\/jats:italic>\u2009=\u20096863), a clinical cohort diagnosed at a MS clinic (<jats:italic>n<\/jats:italic>\u2009=\u2009966), and matched controls (administrative cohort: <jats:italic>n<\/jats:italic>\u2009=\u200931,865; clinical cohort: <jats:italic>n<\/jats:italic>\u2009=\u20094534). In each cohort, the 5\u2009years before a first demyelinating event or MS symptom onset (i.e., index date) were examined. We compared rates of GI\u2010related physician visits and risk of \u22651 GI\u2010related dispensation between MS cases and controls using negative binomial and robust Poisson models. Sex differences were tested using interaction terms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The administrative cohort MS cases had higher rates of physician visits related to gastritis and duodenitis (adjusted rate\/risk ratio (aRR):1.42, 95% CI: 1.10\u20131.83) and diseases of the esophagus (aRR: 1.46, 95% CI: 1.06\u20132.02) prior to the index date. MS cases also had greater risk of at least one dispensation for several drug classes, including constipation\u2010related (aRR: 1.82, 95% CI: 1.50\u20132.22), antiemetics\/antinauseants (aRR: 1.64, 95% CI: 1.43\u20131.89), and propulsives (promotility drugs; aRR: 1.62, 95% CI: 1.47\u20131.79). Men had a disproportionally higher relative risk for propulsives than women (aRR: men\u2009=\u20092.32, 95% CI: 1.79\u20133.00; women\u2009=\u20091.54, 95% CI: 1.36\u20131.72). Several findings were similar in the smaller clinical cohort though none reached statistical significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>GI\u2010related physician visits and drug dispensations were more common in the 5\u2009years before the first demyelinating event versus matched controls. GI symptoms are a measurable feature of the prodromal or early phase of MS, with a sex difference evident.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51945","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T07:14:30Z","timestamp":1703056470000},"page":"185-193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Gastrointestinal conditions in the multiple sclerosis prodrome"],"prefix":"10.1002","volume":"11","author":[{"given":"Fardowsa L. A.","family":"Yusuf","sequence":"first","affiliation":[{"name":"Medicine (Neurology), the Djavad Mowafaghian Centre for Brain Health University of British Columbia  2211 Wesbrook Mall Vancouver British Columbia V6T 2B5 Canada"},{"name":"School of Population and Public Health, University of British Columbia  2206 East Mall Vancouver British Columbia V6T 1Z3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Medicine (Neurology), the Djavad Mowafaghian Centre for Brain Health University of British Columbia  2211 Wesbrook Mall Vancouver British Columbia V6T 2B5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charity","family":"Evans","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan  2A20.4 Health Sciences Bldg, 107 Wiggins Ave Saskatoon Saskatchewan S7N 5E5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Fisk","sequence":"additional","affiliation":[{"name":"Nova Scotia Health and the Departments of Psychiatry, Psychology &amp; Neuroscience, and Medicine Dalhousie University  4066 A.J. Lane Memorial Building, 5909 Veterans' Memorial Lane Halifax Nova Scotia B3H 2E2 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":"Medicine (Neurology), the Djavad Mowafaghian Centre for Brain Health University of British Columbia  2211 Wesbrook Mall Vancouver British Columbia V6T 2B5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth A.","family":"Marrie","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine and Community Health Sciences, Rady Faculty of Health Sciences, Health Sciences Centre Max Rady College of Medicine, University of Manitoba  GF543, 820 Sherbrook Street Winnipeg Manitoba R3A 1R9 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-2535","authenticated-orcid":false,"given":"Helen","family":"Tremlett","sequence":"additional","affiliation":[{"name":"Medicine (Neurology), the Djavad Mowafaghian Centre for Brain Health University of British Columbia  2211 Wesbrook Mall Vancouver British Columbia V6T 2B5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2020.1746645"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518783662"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520908163"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30076-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00519-3"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00686-x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25247"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51476"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103798"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-318444"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13592"},{"key":"e_1_2_8_13_1","unstructured":"British Columbia Ministry of Health.Consolidation File (MSP Registration & Premium Billing). V2.Population Data BC.2017. Data Extract. MOH (2017).http:\/\/www.popdata.bc.ca\/data."},{"key":"e_1_2_8_14_1","unstructured":"British Columbia Ministry of Health.Medical Services Plan (MSP) Payment Information File. V2.Population Data BC.2017. Data Extract. MOH (2017).http:\/\/www.popdata.bc.ca\/data."},{"key":"e_1_2_8_15_1","unstructured":"Canadian Institute for Health Information.Discharge Abstract Database (Hospital Separations). V2.Population Data BC.2022. Data Extract. MOH (2017).http:\/\/www.popdata.bc.ca\/data."},{"key":"e_1_2_8_16_1","unstructured":"BC Ministry of Health.PharmaNet. V2.BC Ministry of Health.2017. Data Extract. Data Stewardship Committee (2017).http:\/\/www.popdata.bc.ca\/data."},{"key":"e_1_2_8_17_1","volume-title":"Health Indicators 2013","author":"Canadian Institute for Health Information and Statistics Canada","year":"2013"},{"key":"e_1_2_8_18_1","unstructured":"Anatomical Therapeutic Chemical (ATC) Classification.World Health Organization.2022[cited 2022 Feb 15].https:\/\/www.who.int\/tools\/atc\u2010ddd\u2010toolkit\/atc\u2010classification."},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181cf6ec0"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100015961"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12990"},{"key":"e_1_2_8_22_1","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2020"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10173821"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2015-311680"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27802"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-021-00156-z"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00460-0"},{"key":"e_1_2_8_28_1","first-page":"15","article-title":"Dysphagia in multiple sclerosis patients: diagnostic and evaluation strategies","volume":"10","author":"Ansari NN","year":"2020","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14326"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2005\/103615"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458516643600"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-020-00676-3"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.7.62"},{"key":"e_1_2_8_34_1","article-title":"From postural orthostatic tachycardia syndrome to radiologically isolated syndrome","volume":"2018","author":"Tripathi R","year":"2018","journal-title":"Case Rep Neurol Med"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1579693"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.5152\/tjg.2020.18850"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.9561"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.101"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/2049-9256-2-4"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15325"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51945","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T18:37:27Z","timestamp":1705862247000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,19]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/acn3.51945"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51945","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,19]]},"assertion":[{"value":"2023-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}