{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T18:39:05Z","timestamp":1793558345061,"version":"4.5.0"},"reference-count":41,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"unspecified","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"crossref","award":["NNF19OC0058628"],"award-info":[{"award-number":["NNF19OC0058628"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hvidovre Hospital Research Foundation","award":["AHH E-21835-31"],"award-info":[{"award-number":["AHH E-21835-31"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,11,19]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To identify early-occurring healthcare and sociodemographic risk factors associated with lower extremity amputation (LEA) by analysing health trajectories up to 10 years before amputation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A national, observational, registry-based matched case\u2013control study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>The Danish universal healthcare system, using national health registers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>We included 2551 individuals who underwent first-time LEA in 2017\u20132018 and matched each to two control groups: (1) The Community Controls Group representing the average population who were matched on age, sex and municipality (n=12\u2009748) and (2) a Diabetes Mellitus\/Peripheral Arterial Disease (DM\/PAD) Control Group matched on age, sex and DM or PAD duration (n=12\u2009478) representing a high-risk population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary outcome measures<\/jats:title>\n                    <jats:p>Presence of healthcare, sociodemographic and medication-related risk factors associated with LEA was evaluated across three time periods leading up to amputation: the Immediate (0\u20132 years prior), Early (2\u20135 years prior) and Long-term (5\u201310 years prior) risk period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Polypharmacy and antibiotic use\u2014particularly dicloxacillin targeting\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      \u2014were strongly associated with LEA across all time periods. Dicloxacillin was prescribed on average 7.8 years prior to major amputation, with long-term ORs of 2.99 (95% CI 2.51 to 3.56) and 2.07 (95% CI 1.75 to 2.46) compared with community and DM\/PAD controls. Opioid and paracetamol use also showed strong associations. Individuals with LEA were more likely to live alone and have lower educational attainment. Frequent dental visits were inversely associated with risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies characteristics associated with LEA, including long-term exposure to dicloxacillin and opioid analgesics, alongside polypharmacy and socioeconomic disadvantage. These factors were detectable up to 10 years before amputation and may serve as early indicators for risk identification and guide targeted general practitioner interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-112203","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T05:30:19Z","timestamp":1765863019000},"page":"e112203","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Identifying long-term healthcare and sociodemographic risk factors for lower extremity amputation: a 10-year national registry-based case\u2013control study in Denmark"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0116-722X","authenticated-orcid":false,"given":"Pia S\u00f8e","family":"Jensen","sequence":"first","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Hvidovre, Hvidovre, 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Gybel","family":"Juul-Larsen","sequence":"additional","affiliation":[{"name":"Hvidovre Hospital, Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"2026010703483572000_15.12.e112203.1","doi-asserted-by":"crossref","first-page":"5169","DOI":"10.1080\/09638288.2023.2291552","article-title":"The experiences and needs of people with dysvascular lower extremity amputations: a qualitative systematic review and meta-synthesis","volume":"46","author":"Cai","year":"2024","journal-title":"Disabil Rehabil"},{"key":"2026010703483572000_15.12.e112203.2","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1080\/09638288.2020.1803999","article-title":"A qualitative study exploring individuals\u2019 experiences living with dysvascular lower limb amputation","volume":"44","author":"MacKay","year":"2022","journal-title":"Disabil 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