{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T06:38:02Z","timestamp":1770100682429,"version":"3.49.0"},"reference-count":12,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U24 AA020794"],"award-info":[{"award-number":["U24 AA020794"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U10 AA013566"],"award-info":[{"award-number":["U10 AA013566"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["1RM1DA055310-01"],"award-info":[{"award-number":["1RM1DA055310-01"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["P01 AA029545-4"],"award-info":[{"award-number":["P01 AA029545-4"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n The Food and Drug Administration\u2019s warning that transmucosal buprenorphine, a partial opioid agonist used to treat opioid use disorder and chronic pain, may cause dental disease opens questions about potential class-wide adverse effects involving more widely prescribed opioid analgesics.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This was a retrospective matched national cohort study of patients in care at the Department of Veterans Affairs (VA) between October 2010-September 2019. Patients prescribed LTOT were matched 1:2 to patients not prescribed LTOT on age, sex, service region, and VA dental coverage. Cox regression models estimated the association between LTOT and a composite infection-related dental outcome (CIDO). Sensitivity analyses excluded patients with cancer, restricted to patients with comprehensive dental coverage, and to patients with \u2265180 days of follow-up time, respectively.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The cohort comprised 2,173,435 patients including 787,825 (36%) receiving LTOT; 612,101 (28%) experienced CIDO. In both simple and multivariable regression models, LTOT exposure was associated with greater CIDO risk; HR (95% CI) =1.24 (1.23, 1.25); aHR (95% CI) =1.08 (1.07, 1.08), respectively; p\u2009<\u20090.001. Sensitivity analyses showed similar results except among patients with full dental coverage for whom CIDO rates were substantially higher and LTOT was not statistically significantly associated with risk.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n he observed positive association between LTOT and CIDO in this large VA sample may inform patient-provider discussions and decision-making around use of LTOT. High CIDO rates among patients with full VA dental coverage may reflect their unique vulnerability to dental infection associated with service-related dental or disabling conditions. Limitations include risk for ascertainment bias, unclear generalizability to a broader clinical population, and the potential for residual confounding.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0341361","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:23:32Z","timestamp":1770056612000},"page":"e0341361","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["The association between long-term opioid therapy and composite infection-related dental outcomes"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0295-7351","authenticated-orcid":true,"given":"Anne C.","family":"Black","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsha S.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James D.","family":"Dziura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Declan T.","family":"Barry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Crystal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Jennifer","family":"Edelman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9345-8552","authenticated-orcid":true,"given":"Gretchen","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Jurasic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0352-0058","authenticated-orcid":true,"given":"Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-7052","authenticated-orcid":true,"given":"Brandon D.L.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Skanderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"Suda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William C.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"pone.0341361.ref001","author":"Department of Veterans Affairs","year":"2024"},{"issue":"3","key":"pone.0341361.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7103a1","article-title":"CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022","volume":"71","author":"D Dowell","year":"2022","journal-title":"MMWR Recomm Rep"},{"key":"pone.0341361.ref003","author":"U.S. Department of Health and Human Services","year":"2019"},{"key":"pone.0341361.ref004","article-title":"Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation","volume":"368","author":"EM Oliva","year":"2020","journal-title":"BMJ"},{"issue":"3","key":"pone.0341361.ref005","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/cpu.30656","article-title":"FDA warns about dental problems with buprenorphine medicines dissolved in the mouth","volume":"24","author":"A Knopf","year":"2022","journal-title":"Child and Adolescent Update"},{"issue":"5","key":"pone.0341361.ref006","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1177\/154405910408300508","article-title":"Oral pilocarpine for treatment of opioid-induced oral dryness in healthy adults","volume":"83","author":"B G\u00f6trick","year":"2004","journal-title":"J Dent Res"},{"issue":"1","key":"pone.0341361.ref007","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00726-011-1163-0","article-title":"Role of the mu-opioid receptor in opioid modulation of immune function","volume":"45","author":"J Ninkovi\u0107","year":"2013","journal-title":"Amino Acids"},{"issue":"1","key":"pone.0341361.ref008","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11606-012-2189-z","article-title":"Receipt of opioid analgesics by HIV-infected and uninfected patients","volume":"28","author":"EJ Edelman","year":"2013","journal-title":"J Gen Intern Med"},{"key":"pone.0341361.ref009","author":"Centers for Disease Control","year":"2024"},{"key":"pone.0341361.ref010","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1089\/aid.2019.0136","article-title":"Strengths and Limitations of the Veterans Aging Cohort Study Index as a Measure of Physiologic Frailty","volume":"35","author":"AC Justice","year":"2019","journal-title":"AIDS Res Hum Retroviruses"},{"key":"pone.0341361.ref011","volume-title":"Eligibility for hospital, nursing home, and domiciliary care","year":"2015"},{"key":"pone.0341361.ref012","volume-title":"Dental care; drugs and medicines for certain disabled veterans; vaccines","year":"2023"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0341361","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:23:35Z","timestamp":1770056615000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0341361"}},"subtitle":[],"editor":[{"given":"Kimberly","family":"Page","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":12,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0341361","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]}}}