{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T09:18:26Z","timestamp":1783502306682,"version":"3.55.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Surg Oncol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Opioid analgesics and benzodiazepines are frequently prescribed to manage pain, anxiety, and insomnia in older adults with gastrointestinal (GI) cancers, yet outcomes of concurrent use are incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Using linked Surveillance, Epidemiology, and End Results (SEER)\u2013Medicare (2014\u20132018), daily exposure was classified as no opioid\/benzodiazepine, opioid only, or opioid\u2013benzodiazepine co-prescription and overdose; falls\/fractures, all-cause hospitalization, and all-cause mortality within 12 months were assessed. Time-varying Cox models compared opioid-only and co-prescription versus no exposure, and for incremental risk, co-prescription versus opioid-only.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 26,896 patients (median age 74 years; 53.1% female), 5086 (18.9%) received concurrent opioid\u2013benzodiazepine prescriptions and 2288 (8.5%) received opioids alone. Within 12 months, among patients unexposed, opioid-only, and co-prescribed, unadjusted first-event rates per 100,000 person-days (95% CI) were: falls\/fractures 27.8 (26.7\u201328.9), 55.0 (47.1\u201363.9), and 61.0 (50.8\u201372.5); all-cause hospitalizations 393.0 (388.0\u2013398.0), 439.0 (410.0\u2013470.0), and 441.0 (406.0\u2013480.0); overdose 1.40 (1.20\u20131.70), 6.20 (3.80\u20139.50), and 8.80 (5.32\u201313.83); and mortality 11.5 (10.8\u201312.2), 20.6 (15.9\u201326.1), and 29.6 (22.8\u201337.9), respectively (global\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u20090.001). In adjusted models versus no exposure, both opioid-only and co-prescribed patients had higher hazards of adverse outcomes. Using opioid-only as reference, co-prescription was associated with incremental hazards of all-cause hospitalization (HR 1.12, 95% CI 1.03\u20131.23) and all-cause mortality (HR 1.35, 95% CI 1.06\u20131.73).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Opioid exposure was associated with elevated risk, while the addition of benzodiazepines conferred incremental increases in hospitalization and mortality versus opioid-only use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1245\/s10434-026-19233-9","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T15:36:10Z","timestamp":1771515370000},"page":"5693-5702","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Double Jeopardy: Risks of Opioid\u2013Benzodiazepine Co-prescription in Older Adults with Gastrointestinal Cancer"],"prefix":"10.1245","volume":"33","author":[{"given":"Areesh","family":"Mevawalla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza","family":"Sarfraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qaidar","family":"Alizai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meher","family":"Angez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odysseas P.","family":"Chatzipanagiotou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mujtaba","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-9870","authenticated-orcid":false,"given":"Timothy M.","family":"Pawlik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"19233_CR1","unstructured":"Global burden of 5 major types of gastrointestinal cancer. Accessed 13 Sep 2025. https:\/\/www.iarc.who.int\/news-events\/global-burden-of-5-major-types-of-gastrointestinal-cancer"},{"issue":"3","key":"19233_CR2","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/S2468-1253(23)00366-7","volume":"9","author":"S Wang","year":"2024","unstructured":"Wang S, Zheng R, Li J, et al. Global, regional, and national lifetime risks of developing and dying from gastrointestinal cancers in 185 countries: a population-based systematic analysis of GLOBOCAN. Lancet Gastroenterol Hepatol. 2024;9(3):229\u201337. https:\/\/doi.org\/10.1016\/S2468-1253(23)00366-7.","journal-title":"Lancet Gastroenterol Hepatol."},{"key":"19233_CR3","unstructured":"ClearNote Health Joins the Pancreatic Cancer Early Detection (PRECEDE) Consortium in New Partnership to Reduce Cancer Mortality. ClearNote Health. Accessed 13 Sep 2025. https:\/\/www.clearnotehealth.com\/press-release\/clearnote-health-joins-the-pancreatic-cancer-early-detection-precede-consortium-in-new-partnership-to-reduce-cancer-mortality\/"},{"key":"19233_CR4","unstructured":"(PDF) Colorectal cancer statistics. 2023. Accessed 13 Sep 2025. https:\/\/www.researchgate.net\/publication\/368883617_Colorectal_cancer_statistics_2023"},{"issue":"4_suppl","key":"19233_CR5","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1200\/JCO.2023.41.4_suppl.311","volume":"41","author":"XS Wang","year":"2023","unstructured":"Wang XS, Hess LM, Shen SE, Gonzalez E, Jomaa MK, Liepa AM. Symptom burden and functioning status in patients with advanced upper gastrointestinal cancers. J Clin Oncol. 2023;41(4_suppl):311\u2013311. https:\/\/doi.org\/10.1200\/JCO.2023.41.4_suppl.311.","journal-title":"J Clin Oncol."},{"issue":"7","key":"19233_CR6","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1093\/jnci\/djaf072","volume":"117","author":"DK Check","year":"2025","unstructured":"Check DK, Soneji S, Cohen HJ, et al. Association of opioid and benzodiazepine coprescribing with adverse events among older adults with cancer. J Natl Cancer Inst. 2025;117(7):1465\u201373. https:\/\/doi.org\/10.1093\/jnci\/djaf072.","journal-title":"J Natl Cancer Inst."},{"issue":"2","key":"19233_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgo.2024.102172","volume":"16","author":"A O\u2019Regan","year":"2025","unstructured":"O\u2019Regan A, Lee JR, McDermott CL, et al. Opioids and benzodiazepines in oncology: perspectives on coprescribing and mitigating risks. J Geriatr Oncol. 2025;16(2):102172. https:\/\/doi.org\/10.1016\/j.jgo.2024.102172.","journal-title":"J Geriatr Oncol."},{"key":"19233_CR8","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j760","volume":"356","author":"EC Sun","year":"2017","unstructured":"Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017;356:j760. https:\/\/doi.org\/10.1136\/bmj.j760.","journal-title":"BMJ."},{"key":"19233_CR9","unstructured":"Association between benzodiazepine use with or without opioid use and all-cause mortality in the United States, 1999-2015 | Clin Pharm Pharmacol | JAMA Netw Open | JAMA Netw. Accessed 13 Sep 2025. https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2773826"},{"issue":"3","key":"19233_CR10","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s40266-022-00929-y","volume":"39","author":"RE Virnes","year":"2022","unstructured":"Virnes RE, Tiihonen M, Karttunen N, van Poelgeest EP, van der Velde N, Hartikainen S. Opioids and falls risk in older adults: a narrative review. Drugs Aging. 2022;39(3):199\u2013207. https:\/\/doi.org\/10.1007\/s40266-022-00929-y.","journal-title":"Drugs Aging."},{"issue":"5","key":"19233_CR11","doi-asserted-by":"publisher","first-page":"3352","DOI":"10.1245\/s10434-025-16904-x","volume":"32","author":"S Zindani","year":"2025","unstructured":"Zindani S, Khalil M, Woldesenbet S, et al. Impact of disability on postoperative outcomes after gastrointestinal cancer surgery. Ann Surg Oncol. 2025;32(5):3352\u20139. https:\/\/doi.org\/10.1245\/s10434-025-16904-x.","journal-title":"Ann Surg Oncol."},{"key":"19233_CR12","first-page":"112","volume":"2013","author":"R Kavuluru","year":"2013","unstructured":"Kavuluru R, Hands I, Durbin EB, Witt L. Automatic extraction of ICD-O-3 primary sites from cancer pathology reports. AMIA Summits Transl Sci Proc. 2013;2013:112\u20136.","journal-title":"AMIA Summits Transl Sci Proc."},{"key":"19233_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmedinf.2022.104739","volume":"162","author":"JA Lossio-Ventura","year":"2022","unstructured":"Lossio-Ventura JA, Song W, Sainlaire M, Dykes PC, Hernandez-Boussard T. Standardizing opioid prescriptions to morphine milligram equivalents from electronic health records. Int J Med Inf. 2022;162:104739. https:\/\/doi.org\/10.1016\/j.ijmedinf.2022.104739.","journal-title":"Int J Med Inf."},{"key":"19233_CR14","unstructured":"CDC. Assess risks and potential harms of opioid use. Overdose prevention. June 24, 2024. Accessed 14 Sep 2025. https:\/\/www.cdc.gov\/overdose-prevention\/hcp\/clinical-care\/assess-risks-of-opioid-use.html"},{"issue":"10","key":"19233_CR15","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.1007\/s11606-020-06577-5","volume":"36","author":"BD Stein","year":"2021","unstructured":"Stein BD, Smart R, Jones CM, Sheng F, Powell D, Sorbero M. Individual and community factors associated with naloxone co-prescribing among long-term opioid patients: a retrospective analysis. J Gen Intern Med. 2021;36(10):2952\u20137. https:\/\/doi.org\/10.1007\/s11606-020-06577-5.","journal-title":"J Gen Intern Med."},{"key":"19233_CR16","doi-asserted-by":"publisher","first-page":"263355652412834","DOI":"10.1177\/26335565241283436","volume":"14","author":"C Loyd","year":"2024","unstructured":"Loyd C, Picken L, Sanders R, Zhang Y, Kennedy RE, Brown CJ. Changes in multimorbidity among hospitalized adults in the US. J Multimorb Comorbidity. 2024;14:26335565241283436. https:\/\/doi.org\/10.1177\/26335565241283436.","journal-title":"J Multimorb Comorbidity."},{"key":"19233_CR17","unstructured":"Medical Care. Accessed 17 Jan 2026. https:\/\/journals.lww.com\/lww-medicalcare\/fulltext\/2017\/07000\/development_of_a_claims_based_frailty_indicator.11.aspx"},{"issue":"Suppl 1","key":"19233_CR18","doi-asserted-by":"publisher","first-page":"i56","DOI":"10.1136\/injuryprev-2019-043521","volume":"27","author":"A Vivolo-Kantor","year":"2021","unstructured":"Vivolo-Kantor A, Pasalic E, Liu S, Martinez PD, Gladden RM. Defining indicators for drug overdose emergency department visits and hospitalisations in ICD-10-CM coded discharge data. Inj Prev. 2021;27(Suppl 1):i56\u201361. https:\/\/doi.org\/10.1136\/injuryprev-2019-043521.","journal-title":"Inj Prev."},{"key":"19233_CR19","unstructured":"Falls Prevention. Accessed 14 Sep 2025. https:\/\/www.apha.org\/policy-and-advocacy\/public-health-policy-briefs\/policy-database\/2024\/01\/16\/falls-prevention"},{"issue":"5","key":"19233_CR20","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1111\/jgs.15864","volume":"67","author":"C Pandya","year":"2019","unstructured":"Pandya C, Magnuson A, Flannery M, et al. Association between symptom burden and physical function in older patients with cancer. J Am Geriatr Soc. 2019;67(5):998\u20131004. https:\/\/doi.org\/10.1111\/jgs.15864.","journal-title":"J Am Geriatr Soc."},{"issue":"3","key":"19233_CR21","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1002\/cncr.33963","volume":"128","author":"T Salz","year":"2022","unstructured":"Salz T, Mishra A, Gennarelli RL, et al. Safety of opioid prescribing among older cancer survivors. Cancer. 2022;128(3):570\u20138. https:\/\/doi.org\/10.1002\/cncr.33963.","journal-title":"Cancer."},{"issue":"2","key":"19233_CR22","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1111\/j.1365-2125.2008.03185.x","volume":"66","author":"CS van der Hooft","year":"2008","unstructured":"van der Hooft CS, Schoofs MWCJ, Ziere G, et al. Inappropriate benzodiazepine use in older adults and the risk of fracture. Br J Clin Pharmacol. 2008;66(2):276\u201382. https:\/\/doi.org\/10.1111\/j.1365-2125.2008.03185.x.","journal-title":"Br J Clin Pharmacol."},{"issue":"2","key":"19233_CR23","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2023-079347","volume":"14","author":"MT Bjelkar\u00f8y","year":"2024","unstructured":"Bjelkar\u00f8y MT, Simonsen TB, Siddiqui TG, et al. Mortality and health-related quality of life in older adults with long-term use of opioids, z-hypnotics or benzodiazepines: a prospective observational study at 5 years follow-up. BMJ Open. 2024;14(2):e079347. https:\/\/doi.org\/10.1136\/bmjopen-2023-079347.","journal-title":"BMJ Open."},{"key":"19233_CR24","doi-asserted-by":"publisher","unstructured":"Mortality and concurrent use of opioids and hypnotics in older patients: a retrospective cohort study | PLOS Med. Accessed 17 Jan 2026. https:\/\/journals.plos.org\/plosmedicine\/article?id=https:\/\/doi.org\/10.1371\/journal.pmed.1003709","DOI":"10.1371\/journal.pmed.1003709"},{"key":"19233_CR25","doi-asserted-by":"publisher","first-page":"18964","DOI":"10.1038\/s41598-020-75888-8","volume":"10","author":"TI Chang","year":"2020","unstructured":"Chang TI, Park H, Kim DW, et al. Polypharmacy, hospitalization, and mortality risk: a nationwide cohort study. Sci Rep. 2020;10:18964. https:\/\/doi.org\/10.1038\/s41598-020-75888-8.","journal-title":"Sci Rep."},{"key":"19233_CR26","unstructured":"Exposure-response association between concurrent opioid and benzodiazepine use and risk of opioid-related overdose in Medicare Part D beneficiaries | Subst Use Addiction Med | JAMA Netw Open | JAMA Netw. Accessed 13 Sep 2025. https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2685628"},{"key":"19233_CR27","doi-asserted-by":"publisher","unstructured":"Liu S. Trends in nonfatal and fatal overdoses involving benzodiazepines: 38 states and the District of Columbia, 2019\u20132020. MMWR Morb Mortal Wkly Rep. 2021;70. https:\/\/doi.org\/10.15585\/mmwr.mm7034a2","DOI":"10.15585\/mmwr.mm7034a2"},{"issue":"3","key":"19233_CR28","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1002\/cpt.2027","volume":"109","author":"MH Algera","year":"2021","unstructured":"Algera MH, Olofsen E, Moss L, et al. Tolerance to opioid-induced respiratory depression in chronic high-dose opioid users: a model-based comparison with opioid-na\u00efve individuals. Clin Pharmacol Ther. 2021;109(3):637\u201345. https:\/\/doi.org\/10.1002\/cpt.2027.","journal-title":"Clin Pharmacol Ther."},{"issue":"12","key":"19233_CR29","doi-asserted-by":"publisher","first-page":"3376","DOI":"10.3390\/jcm13123376","volume":"13","author":"GHM Wang","year":"2024","unstructured":"Wang GHM, Hincapie-Castillo JM, Gellad WF, et al. Association between opioid\u2013benzodiazepine trajectories and injurious fall risk among US Medicare beneficiaries. J Clin Med. 2024;13(12):3376. https:\/\/doi.org\/10.3390\/jcm13123376.","journal-title":"J Clin Med."},{"issue":"4","key":"19233_CR30","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1007\/s40122-024-00619-0","volume":"13","author":"L Huang","year":"2024","unstructured":"Huang L, Zhang T, Wang K, Chang B, Fu D, Chen X. Postoperative multimodal analgesia strategy for enhanced recovery after surgery in elderly colorectal cancer patients. Pain Ther. 2024;13(4):745\u201366. https:\/\/doi.org\/10.1007\/s40122-024-00619-0.","journal-title":"Pain Ther."},{"issue":"3","key":"19233_CR31","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_100038","volume":"44","author":"LA Petrillo","year":"2024","unstructured":"Petrillo LA, Jones KF, El-Jawahri A, Sanders J, Greer JA, Temel JS. Why and how to integrate early palliative care into cutting-edge personalized cancer care. Am Soc Clin Oncol Educ Book. 2024;44(3):e100038. https:\/\/doi.org\/10.1200\/EDBK_100038.","journal-title":"Am Soc Clin Oncol Educ Book."},{"key":"19233_CR32","unstructured":"World guidelines for falls prevention and management for older adults: a global initiative | Age Ageing | Oxford Academic. Accessed 18 Jan 2026. https:\/\/academic.oup.com\/ageing\/article\/51\/9\/afac205\/6730755"},{"key":"19233_CR33","unstructured":"Chippa V, Roy K. Geriatric cognitive decline and polypharmacy. In: StatPearls. StatPearls Publishing; 2025. Accessed 16 Sep 2025. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK574575\/"},{"issue":"5","key":"19233_CR34","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.gerinurse.2007.10.016","volume":"29","author":"KA McMichael","year":"2008","unstructured":"McMichael KA, Vander Bilt J, Lavery L, Rodriguez E, Ganguli M. Simple balance and mobility tests can assess falls risk when cognition is impaired. Geriatr Nurs N Y N. 2008;29(5):311\u201323. https:\/\/doi.org\/10.1016\/j.gerinurse.2007.10.016.","journal-title":"Geriatr Nurs N Y N."},{"issue":"7","key":"19233_CR35","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1093\/jnci\/djz201","volume":"112","author":"DK Check","year":"2019","unstructured":"Check DK, Winn AN, Fergestrom N, Reeder-Hayes KE, Neuner JM, Roberts AW. Concurrent opioid and benzodiazepine prescriptions among older women diagnosed with breast cancer. JNCI J Natl Cancer Inst. 2019;112(7):765\u20138. https:\/\/doi.org\/10.1093\/jnci\/djz201.","journal-title":"JNCI J Natl Cancer Inst."},{"issue":"4","key":"19233_CR36","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1111\/jgs.18728","volume":"72","author":"S Chae","year":"2024","unstructured":"Chae S, Lee E, Lindenberg J, Shen K, Anderson TS. Evaluation of a benzodiazepine deprescribing quality improvement initiative for older adults in primary care. J Am Geriatr Soc. 2024;72(4):1234\u201341. https:\/\/doi.org\/10.1111\/jgs.18728.","journal-title":"J Am Geriatr Soc."},{"key":"19233_CR37","unstructured":"Risky prescribing and the epidemic of deaths from falls | Health Pol | JAMA Health Forum | JAMA Netw. Accessed 13 Sep 2025. https:\/\/jamanetwork.com\/journals\/jama-health-forum\/fullarticle\/2837039"},{"key":"19233_CR38","unstructured":"Abuse NI on D. NIDA.NIH.GOV | National Institute on Drug Abuse (NIDA). November 14, 2025. Accessed 13 Sep 2025. https:\/\/nida.nih.gov\/"}],"container-title":["Annals of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-026-19233-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1245\/s10434-026-19233-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-026-19233-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T18:28:41Z","timestamp":1778869721000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1245\/s10434-026-19233-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["19233"],"URL":"https:\/\/doi.org\/10.1245\/s10434-026-19233-9","relation":{},"ISSN":["1068-9265","1534-4681"],"issn-type":[{"value":"1068-9265","type":"print"},{"value":"1534-4681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]},"assertion":[{"value":"6 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}