{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T19:55:41Z","timestamp":1774900541548,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"Miami VA Healthcare System - GRECC"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Aging Clin Exp Res"],"published-print":{"date-parts":[[2022,8]]},"DOI":"10.1007\/s40520-022-02125-9","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T06:03:36Z","timestamp":1651817016000},"page":"1837-1843","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The cross-sectional association of frailty with chronic past and current use of benzodiazepine drugs"],"prefix":"10.1007","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0045-4339","authenticated-orcid":false,"given":"Christian J.","family":"Gomez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7181-4536","authenticated-orcid":false,"given":"Alma Diaz","family":"Quinones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1972-2922","authenticated-orcid":false,"given":"Amy Melissa","family":"Gonell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4404-3235","authenticated-orcid":false,"given":"Tesil Nedumkallel","family":"Sani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-3969","authenticated-orcid":false,"given":"Otoniel","family":"Ysea-Hill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1275-3339","authenticated-orcid":false,"given":"Dhanya","family":"Baskaran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3069-8502","authenticated-orcid":false,"given":"Jorge G.","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"2125_CR1","doi-asserted-by":"publisher","first-page":"M146","DOI":"10.1093\/gerona\/56.3.m146","volume":"56","author":"LP Fried","year":"2001","unstructured":"Fried LP, Tangen CM, Walston J et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146\u2013M156. https:\/\/doi.org\/10.1093\/gerona\/56.3.m146","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2125_CR2","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1093\/gerona\/gly232","volume":"74","author":"AR Orkaby","year":"2019","unstructured":"Orkaby AR, Nussbaum L, Ho YL et al (2019) The burden of frailty among U.S. veterans and its association with mortality, 2002\u20132012. J Gerontol A Biol Sci Med Sci 74:1257\u20131264. https:\/\/doi.org\/10.1093\/gerona\/gly232","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2125_CR3","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1093\/gerona\/59.3.m255","volume":"59","author":"LP Fried","year":"2004","unstructured":"Fried LP, Ferrucci L, Darer J et al (2004) Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci 59:255\u2013263. https:\/\/doi.org\/10.1093\/gerona\/59.3.m255","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2125_CR4","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1111\/jgs.15928","volume":"67","author":"J Walston","year":"2019","unstructured":"Walston J, Bandeen-Roche K, Buta B et al (2019) Moving frailty toward clinical practice: NIA intramural frailty science symposium summary. J Am Geriatr Soc 67:1559\u20131564. https:\/\/doi.org\/10.1111\/jgs.15928","journal-title":"J Am Geriatr Soc"},{"key":"2125_CR5","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cger.2010.08.008","volume":"27","author":"K Rockwood","year":"2011","unstructured":"Rockwood K, Mitnitski A (2011) Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med 27:17\u201326. https:\/\/doi.org\/10.1016\/j.cger.2010.08.008","journal-title":"Clin Geriatr Med"},{"key":"2125_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178383","volume":"12","author":"Z Feng","year":"2017","unstructured":"Feng Z, Lugtenberg M, Franse C et al (2017) Risk factors and protective factors associated with incident or increase of frailty among community-dwelling older adults: a systematic review of longitudinal studies. PLoS ONE 12:e0178383. https:\/\/doi.org\/10.1371\/journal.pone.0178383","journal-title":"PLoS ONE"},{"key":"2125_CR7","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1111\/j.1532-5415.2008.01845.x","volume":"56","author":"SE Espinoza","year":"2008","unstructured":"Espinoza SE, Hazuda HP (2008) Frailty in older Mexican-American and European-American adults: is there an ethnic disparity? J Am Geriatr Soc 56:1744\u20131749. https:\/\/doi.org\/10.1111\/j.1532-5415.2008.01845.x","journal-title":"J Am Geriatr Soc"},{"key":"2125_CR8","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1093\/gerona\/gly110","volume":"74","author":"DL Vetrano","year":"2019","unstructured":"Vetrano DL, Palmer K, Marengoni A et al (2019) Frailty and multimorbidity: a systematic review and meta-analysis. J Gerontol A Biol Sci Med Sci 74:659\u2013666. https:\/\/doi.org\/10.1093\/gerona\/gly110","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2125_CR9","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1016\/j.jamda.2016.04.021","volume":"17","author":"N Veronese","year":"2016","unstructured":"Veronese N, Stubbs B, Fontana L et al (2016) Frailty is associated with an increased risk of incident type 2 diabetes in the elderly. J Am Med Dir Assoc 17:902\u2013907. https:\/\/doi.org\/10.1016\/j.jamda.2016.04.021","journal-title":"J Am Med Dir Assoc"},{"key":"2125_CR10","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/jgs.13877","volume":"64","author":"KM Jamsen","year":"2016","unstructured":"Jamsen KM, Bell JS, Hilmer SN et al (2016) Effects of changes in number of medications and drug burden index exposure on transitions between frailty states and death: the concord health and ageing in men project cohort study. J Am Geriatr Soc 64:89\u201395. https:\/\/doi.org\/10.1111\/jgs.13877","journal-title":"J Am Geriatr Soc"},{"key":"2125_CR11","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1002\/pds.1367","volume":"16","author":"R Paulose-Ram","year":"2007","unstructured":"Paulose-Ram R, Safran MA, Jonas BS et al (2007) Trends in psychotropic medication use among U.S. adults. Pharmacoepidemiol Drug Saf 16:560\u201370. https:\/\/doi.org\/10.1002\/pds.1367","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2125_CR12","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s002280100326","volume":"57","author":"A Fourrier","year":"2001","unstructured":"Fourrier A, Letenneur L, Dartigues JF et al (2001) Benzodiazepine use in an elderly community-dwelling population. Characteristics of users and factors associated with subsequent use. Eur J Clin Pharmacol 57:419\u201325. https:\/\/doi.org\/10.1007\/s002280100326","journal-title":"Eur J Clin Pharmacol"},{"key":"2125_CR13","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/sj.bjp.0706796","volume":"148","author":"C Campo-Soria","year":"2006","unstructured":"Campo-Soria C, Chang Y, Weiss DS (2006) Mechanism of action of benzodiazepines on GABAA receptors. Br J Pharmacol 148:984\u2013990. https:\/\/doi.org\/10.1038\/sj.bjp.0706796","journal-title":"Br J Pharmacol"},{"key":"2125_CR14","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1038\/81800","volume":"3","author":"RJ Walters","year":"2000","unstructured":"Walters RJ, Hadley SH, Morris KD et al (2000) Benzodiazepines act on GABAA receptors via two distinct and separable mechanisms. Nat Neurosci 3:1274\u20131281. https:\/\/doi.org\/10.1038\/81800","journal-title":"Nat Neurosci"},{"key":"2125_CR15","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1016\/j.mayocp.2016.07.024","volume":"91","author":"M Markota","year":"2016","unstructured":"Markota M, Rummans TA, Bostwick JM et al (2016) Benzodiazepine use in older adults: dangers, management, and alternative therapies. Mayo Clin Proc 91:1632\u20131639. https:\/\/doi.org\/10.1016\/j.mayocp.2016.07.024","journal-title":"Mayo Clin Proc"},{"key":"2125_CR16","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.jamda.2018.07.008","volume":"19","author":"P Martinot","year":"2018","unstructured":"Martinot P, Landr\u00e9 B, Zins M et al (2018) Association between potentially inappropriate medications and frailty in the early old age: a longitudinal study in the GAZEL cohort. J Am Med Dir Assoc 19:967-973.e3. https:\/\/doi.org\/10.1016\/j.jamda.2018.07.008","journal-title":"J Am Med Dir Assoc"},{"key":"2125_CR17","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1111\/j.1532-5415.2012.04054.x","volume":"60","author":"RM Collard","year":"2012","unstructured":"Collard RM, Boter H, Schoevers RA et al (2012) Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc 60:1487\u201392. https:\/\/doi.org\/10.1111\/j.1532-5415.2012.04054.x","journal-title":"J Am Geriatr Soc"},{"key":"2125_CR18","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/0024-3205(93)90293-c","volume":"52","author":"X Canat","year":"1993","unstructured":"Canat X, Carayon P, Bouaboula M et al (1993) Distribution profile and properties of peripheral-type benzodiazepine receptors on human hemopoietic cells. Life Sci 52:107\u2013118. https:\/\/doi.org\/10.1016\/0024-3205(93)90293-c","journal-title":"Life Sci"},{"key":"2125_CR19","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/s0197-0186(01)00118-8","volume":"40","author":"P Casellas","year":"2002","unstructured":"Casellas P, Galiegue S, Basile AS (2002) Peripheral benzodiazepine receptors and mitochondrial function. Neurochem Int 40:475\u2013486. https:\/\/doi.org\/10.1016\/s0197-0186(01)00118-8","journal-title":"Neurochem Int"},{"key":"2125_CR20","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/0306-4530(93)90051-l","volume":"18","author":"C Ferrarese","year":"1993","unstructured":"Ferrarese C, Appollonio I, Bianchi G et al (1993) Benzodiazepine receptors and diazepam binding inhibitor: a possible link between stress, anxiety and the immune system. Psychoneuroendocrinology 18:3\u201322. https:\/\/doi.org\/10.1016\/0306-4530(93)90051-l","journal-title":"Psychoneuroendocrinology"},{"key":"2125_CR21","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1001\/jamainternmed.2014.7663","volume":"175","author":"SL Gray","year":"2015","unstructured":"Gray SL, Anderson ML, Dublin S et al (2015) Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med 175:401\u2013407. https:\/\/doi.org\/10.1001\/jamainternmed.2014.7663","journal-title":"JAMA Intern Med"},{"key":"2125_CR22","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1093\/gerona\/62.7.722","volume":"62","author":"K Rockwood","year":"2007","unstructured":"Rockwood K, Mitnitski A (2007) Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci 62:722\u2013727. https:\/\/doi.org\/10.1093\/gerona\/62.7.722","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2125_CR23","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1093\/ageing\/aft160","volume":"43","author":"M Cesari","year":"2014","unstructured":"Cesari M, Gambassi G, van Kan GA et al (2014) The frailty phenotype and the frailty index: different instruments for different purposes. Age Ageing 43:10\u201312. https:\/\/doi.org\/10.1093\/ageing\/aft160","journal-title":"Age Ageing"},{"key":"2125_CR24","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1471-2318-8-24","volume":"8","author":"SD Searle","year":"2008","unstructured":"Searle SD, Mitnitski A, Gahbauer EA et al (2008) A standard procedure for creating a frailty index. BMC Geriatr 8:24. https:\/\/doi.org\/10.1186\/1471-2318-8-24","journal-title":"BMC Geriatr"},{"key":"2125_CR25","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.jamda.2019.09.017","volume":"21","author":"G Kojima","year":"2020","unstructured":"Kojima G, Walters K, Iliffe S et al (2020) Marital status and risk of physical frailty: a systematic review and meta-analysis. J Am Med Dir Assoc 21:322\u2013330. https:\/\/doi.org\/10.1016\/j.jamda.2019.09.017","journal-title":"J Am Med Dir Assoc"},{"key":"2125_CR26","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.exger.2016.01.008","volume":"76","author":"A Buch","year":"2016","unstructured":"Buch A, Carmeli E, Boker LK et al (2016) Muscle function and fat content in relation to sarcopenia, obesity and frailty of old age\u2014an overview. Exp Gerontol 76:25\u201332. https:\/\/doi.org\/10.1016\/j.exger.2016.01.008","journal-title":"Exp Gerontol"},{"key":"2125_CR27","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1684\/pnv.2018.0755","volume":"16","author":"C B\u00e9rard","year":"2018","unstructured":"B\u00e9rard C, McCambridge C, Sourdet S et al (2018) Benzodiazepines and frail elderly people: how prescribing can be optimized? Geriatr Psychol Neuropsychiatr Vieil 16:359\u2013366. https:\/\/doi.org\/10.1684\/pnv.2018.0755","journal-title":"Geriatr Psychol Neuropsychiatr Vieil"},{"key":"2125_CR28","doi-asserted-by":"publisher","first-page":"3252","DOI":"10.1001\/archinte.160.21.3252","volume":"160","author":"Z Agha","year":"2000","unstructured":"Agha Z, Lofgren RP, VanRuiswyk JV et al (2000) Are patients at Veterans Affairs medical centers sicker? A comparative analysis of health status and medical resource use. Arch Intern Med 160:3252\u20133257. https:\/\/doi.org\/10.1001\/archinte.160.21.3252","journal-title":"Arch Intern Med"},{"key":"2125_CR29","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1111\/jgs.12417","volume":"61","author":"SN Hastings","year":"2013","unstructured":"Hastings SN, Smith VA, Weinberger M et al (2013) Health services use of older veterans treated and released from veterans affairs medical center emergency departments. J Am Geriatr Soc 61:1515\u20131521. https:\/\/doi.org\/10.1111\/jgs.12417","journal-title":"J Am Geriatr Soc"},{"key":"2125_CR30","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.mad.2019.111119","volume":"181","author":"SN Hilmer","year":"2019","unstructured":"Hilmer SN, Wu H, Zhang M (2019) Biology of frailty: Implications for clinical pharmacology and drug therapy in frail older people. Mech Ageing Dev 181:22\u201328. https:\/\/doi.org\/10.1016\/j.mad.2019.111119","journal-title":"Mech Ageing Dev"},{"key":"2125_CR31","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1002\/pds.908","volume":"13","author":"G Bartlett","year":"2004","unstructured":"Bartlett G, Abrahamowicz M, Tamblyn R et al (2004) Longitudinal patterns of new Benzodiazepine use in the elderly. Pharmacoepidemiol Drug Saf 13:669\u2013682. https:\/\/doi.org\/10.1002\/pds.908","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2125_CR32","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1111\/j.1532-5415.2005.53108.x","volume":"53","author":"R Tamblyn","year":"2005","unstructured":"Tamblyn R, Abrahamowicz M, du Berger R et al (2005) A 5-year prospective assessment of the risk associated with individual benzodiazepines and doses in new elderly users. J Am Geriatr Soc 53:233\u2013241. https:\/\/doi.org\/10.1111\/j.1532-5415.2005.53108.x","journal-title":"J Am Geriatr Soc"},{"key":"2125_CR33","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1111\/jgs.14759","volume":"65","author":"JT Hanlon","year":"2017","unstructured":"Hanlon JT, Zhao X, Naples JG et al (2017) Central nervous system medication burden and serious falls in older nursing home residents. J Am Geriatr Soc 65:1183\u20131189. https:\/\/doi.org\/10.1111\/jgs.14759","journal-title":"J Am Geriatr Soc"},{"key":"2125_CR34","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.2147\/cia.S105714","volume":"11","author":"AE Kane","year":"2016","unstructured":"Kane AE, Hilmer SN, Mach J et al (2016) Animal models of frailty: current applications in clinical research. Clin Interv Aging 11:1519\u20131529. https:\/\/doi.org\/10.2147\/cia.S105714","journal-title":"Clin Interv Aging"},{"key":"2125_CR35","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1002\/ps.544","volume":"58","author":"AG Renwick","year":"2002","unstructured":"Renwick AG (2002) Pesticide residue analysis and its relationship to hazard characterisation (ADI\/ARfD) and intake estimations (NEDI\/NESTI). Pest Manag Sci 58:1073\u20131082. https:\/\/doi.org\/10.1002\/ps.544","journal-title":"Pest Manag Sci"}],"container-title":["Aging Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40520-022-02125-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40520-022-02125-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40520-022-02125-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T03:39:45Z","timestamp":1657856385000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40520-022-02125-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,6]]},"references-count":35,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["2125"],"URL":"https:\/\/doi.org\/10.1007\/s40520-022-02125-9","relation":{},"ISSN":["1720-8319"],"issn-type":[{"value":"1720-8319","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,6]]},"assertion":[{"value":"21 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships, which have or could be perceived to have influenced the work reported in this article. This material is the result of work supported by resources and the use of facilities at the Miami VA Healthcare System GRECC.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of ineterest"}},{"value":"This research study was conducted retrospectively from data obtained for clinical purposes. We consulted extensively with the IRB of the Miami Veteran\u2019s Affair Medical Center who determined that our study did not need ethical approval. An IRB official waiver of ethical approval was granted from the IRB of the Miami Veteran\u2019s Affair Medical Center.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was waived in this cross-sectional chart review study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"There were no animals involved in this study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and animal rights"}}]}}