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      Benzodiazepine Receptor Agonists Use and Cessation Among Multimorbid Older Adults with Polypharmacy: Secondary Analysis from the OPERAM Trial

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          Abstract

          Background

          Benzodiazepine receptor agonists (BZRAs) are commonly prescribed in older adults despite an unfavorable risk–benefit ratio. Hospitalizations may provide a unique opportunity to initiate BZRA cessation, yet little is known about cessation during and after hospitalization. We aimed to measure the prevalence of BZRA use before hospitalization and the rate of cessation 6 months later, and to identify factors associated with these outcomes.

          Methods

          We conducted a secondary analysis of a cluster randomized controlled trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly [OPERAM]), comparing usual care and in-hospital pharmacotherapy optimization in adults aged 70 years or over with multimorbidity and polypharmacy in four European countries. BZRA cessation was defined as taking one or more BZRA before hospitalization and not taking any BZRA at the 6-month follow-up. Multivariable logistic regression was performed to identify factors associated with BZRA use before hospitalization and with cessation at 6 months.

          Results

          Among 1601 participants with complete 6-month follow-up data, 378 (23.6%) were BZRA users before hospitalization. Female sex (odds ratio [OR] 1.52 [95% confidence interval 1.18–1.96]), a higher reported level of depression/anxiety (OR up to 2.45 [1.54–3.89]), a higher number of daily drugs (OR 1.08 [1.05–1.12]), use of an antidepressant (OR 1.74 [1.31–2.31]) or an antiepileptic (OR 1.46 [1.02–2.07]), and trial site were associated with BZRA use. Diabetes mellitus (OR 0.60 [0.44–0.80]) was associated with a lower probability of BZRA use. BZRA cessation occurred in 86 BZRA users (22.8%). Antidepressant use (OR 1.74 [1.06–2.86]) and a history of falling in the previous 12 months (OR 1.75 [1.10–2.78]) were associated with higher BZRA cessation, and chronic obstructive pulmonary disease (COPD) (OR 0.45 [0.20–0.91]) with lower BZRA cessation.

          Conclusion

          BZRA prevalence was high among included multimorbid older adults, and BZRA cessation occurred in almost a quarter of them within 6 months after hospitalization. Targeted BZRA deprescribing programs could further enhance cessation. Specific attention is needed for females, central nervous system-acting co-medication, and COPD co-morbidity.

          Registration

          ClinicalTrials.gov identifier: NCT02986425. December 8, 2016.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40266-023-01029-1.

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          Most cited references48

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          STOPP/START criteria for potentially inappropriate prescribing in older people: version 2

          Purpose: screening tool of older people's prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required. Methods: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology. Results: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines. Conclusion: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts.
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            American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults

            (2019)
            The American Geriatrics Society (AGS) Beers Criteria® (AGS Beers Criteria®) for Potentially Inappropriate Medication (PIM) Use in Older Adults are widely used by clinicians, educators, researchers, healthcare administrators, and regulators. Since 2011, the AGS has been the steward of the criteria and has produced updates on a 3-year cycle. The AGS Beers Criteria® is an explicit list of PIMs that are typically best avoided by older adults in most circumstances or under specific situations, such as in certain diseases or conditions. For the 2019 update, an interdisciplinary expert panel reviewed the evidence published since the last update (2015) to determine if new criteria should be added or if existing criteria should be removed or undergo changes to their recommendation, rationale, level of evidence, or strength of recommendation. J Am Geriatr Soc 67:674-694, 2019.
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              What is polypharmacy? A systematic review of definitions

              Background Multimorbidity and the associated use of multiple medicines (polypharmacy), is common in the older population. Despite this, there is no consensus definition for polypharmacy. A systematic review was conducted to identify and summarise polypharmacy definitions in existing literature. Methods The reporting of this systematic review conforms to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. MEDLINE (Ovid), EMBASE and Cochrane were systematically searched, as well as grey literature, to identify articles which defined the term polypharmacy (without any limits on the types of definitions) and were in English, published between 1st January 2000 and 30th May 2016. Definitions were categorised as i. numerical only (using the number of medications to define polypharmacy), ii. numerical with an associated duration of therapy or healthcare setting (such as during hospital stay) or iii. Descriptive (using a brief description to define polypharmacy). Results A total of 1156 articles were identified and 110 articles met the inclusion criteria. Articles not only defined polypharmacy but associated terms such as minor and major polypharmacy. As a result, a total of 138 definitions of polypharmacy and associated terms were obtained. There were 111 numerical only definitions (80.4% of all definitions), 15 numerical definitions which incorporated a duration of therapy or healthcare setting (10.9%) and 12 descriptive definitions (8.7%). The most commonly reported definition of polypharmacy was the numerical definition of five or more medications daily (n = 51, 46.4% of articles), with definitions ranging from two or more to 11 or more medicines. Only 6.4% of articles classified the distinction between appropriate and inappropriate polypharmacy, using descriptive definitions to make this distinction. Conclusions Polypharmacy definitions were variable. Numerical definitions of polypharmacy did not account for specific comorbidities present and make it difficult to assess safety and appropriateness of therapy in the clinical setting.
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                Author and article information

                Contributors
                francois-xavier.sibille@chuuclnamur.uclouvain.be
                Journal
                Drugs Aging
                Drugs Aging
                Drugs & Aging
                Springer International Publishing (Cham )
                1170-229X
                1179-1969
                23 May 2023
                23 May 2023
                2023
                : 40
                : 6
                : 551-561
                Affiliations
                [1 ]Department of Geriatric Medicine, CHU UCL Namur, Avenue Dr Gaston Therasse, 1, 5530 Yvoir, Belgium
                [2 ]GRID grid.7942.8, ISNI 0000 0001 2294 713X, Institute of Health and Society, , Université Catholique de Louvain, ; Brussels, Belgium
                [3 ]GRID grid.7942.8, ISNI 0000 0001 2294 713X, Clinical Pharmacy Research Group, Louvain Drug Research Institute, , Université Catholique de Louvain, ; Brussels, Belgium
                [4 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Institute of Primary Health Care (BIHAM), , University of Bern, ; Bern, Switzerland
                [5 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Department of General Internal Medicine, Inselspital, Bern University Hospital, , University of Bern, ; Bern, Switzerland
                [6 ]GRID grid.5477.1, ISNI 0000000120346234, Department of Geriatric Medicine, University Medical Center Utrecht, , Utrecht University, ; Utrecht, The Netherlands
                [7 ]GRID grid.7872.a, ISNI 0000000123318773, Department of Medicine, School of Medicine, , University College Cork, ; Cork, Republic of Ireland
                [8 ]GRID grid.48769.34, ISNI 0000 0004 0461 6320, Department of Pharmacy, , Cliniques Universitaires Saint-Luc, ; Brussels, Belgium
                [9 ]GRID grid.6612.3, ISNI 0000 0004 1937 0642, Institute of Pharmaceutical Medicine (ECPM), , University of Basel, ; Basel, Switzerland
                [10 ]Department of Pharmacy, CHU UCL Namur, Yvoir, Belgium
                Author information
                http://orcid.org/0000-0003-4173-8581
                Article
                1029
                10.1007/s40266-023-01029-1
                10232614
                37221407
                b6fd6451-853a-46a6-a65f-b74f65410a6e
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 4 April 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002661, Fonds De La Recherche Scientifique—FNRS;
                Award ID: Clinical Master Specialist Applicant for a Ph.D
                Award Recipient :
                Funded by: Swiss National Science Foundation
                Award ID: SNSF 320030_188549
                Award ID: 325130_204361
                Funded by: FundRef http://dx.doi.org/10.13039/501100007601, Horizon 2020;
                Award ID: 634238
                Categories
                Original Research Article
                Custom metadata
                © Springer Nature Switzerland AG 2023

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