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      Quantification of anticholinergic and sedative drug load with the Drug Burden Index: a review of outcomes and methodological quality of studies

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          Abstract

          Purpose

          The Drug Burden Index (DBI) is a non-invasive method to quantify patients’ anticholinergic and sedative drug burden from their prescriptions. This systematic review aimed to summarise the evidence on the associations between the DBI and clinical outcomes and methodological quality of studies.

          Methods

          A search in PubMed and Embase (search terms: ‘drug’, ‘burden’, and ‘index’) was performed and experts were contacted. We excluded publications that did not report empirical results or clinical outcomes. Methodological quality was assessed using the Newcastle-Ottawa Scale. Potential omissions of relevant clinical outcomes and populations were studied.

          Results

          Of the 2998 identified publications, 21 were eligible. Overall, methodological quality of studies was good. In all but one study, adjustment was made for prevalent co-morbidity. The DBI was examined in diverse older individuals, i.e. both males and females from different settings and countries. However, no studies were conducted in other relevant patient groups, e.g. psychiatric patients. Exposure to anticholinergic and sedative drugs was thoroughly ascertained, though the specific calculation of the DBI differed across studies. Outcomes were assessed from medical records, record linkage or validated objective tests or questionnaires. Many studies found associations between the DBI and outcomes including hospitalisation, physical and cognitive function. Cognitive function and quality of life were understudied and the number and scope of longitudinal studies was limited.

          Conclusions

          An accumulating body of evidence supports the validity of the DBI. Longitudinal studies of cognitive function and quality of life and in other patient groups, e.g. psychiatric patients, are warranted.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s00228-016-2162-6) contains supplementary material, which is available to authorized users.

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          Most cited references39

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          The anticholinergic risk scale and anticholinergic adverse effects in older persons.

          Adverse effects of anticholinergic medications may contribute to events such as falls, delirium, and cognitive impairment in older patients. To further assess this risk, we developed the Anticholinergic Risk Scale (ARS), a ranked categorical list of commonly prescribed medications with anticholinergic potential. The objective of this study was to determine if the ARS score could be used to predict the risk of anticholinergic adverse effects in a geriatric evaluation and management (GEM) cohort and in a primary care cohort. Medical records of 132 GEM patients were reviewed retrospectively for medications included on the ARS and their resultant possible anticholinergic adverse effects. Prospectively, we enrolled 117 patients, 65 years or older, in primary care clinics; performed medication reconciliation; and asked about anticholinergic adverse effects. The relationship between the ARS score and the risk of anticholinergic adverse effects was assessed using Poisson regression analysis. Higher ARS scores were associated with increased risk of anticholinergic adverse effects in the GEM cohort (crude relative risk [RR], 1.5; 95% confidence interval [CI], 1.3-1.8) and in the primary care cohort (crude RR, 1.9; 95% CI, 1.5-2.4). After adjustment for age and the number of medications, higher ARS scores increased the risk of anticholinergic adverse effects in the GEM cohort (adjusted RR, 1.3; 95% CI, 1.1-1.6; c statistic, 0.74) and in the primary care cohort (adjusted RR, 1.9; 95% CI, 1.5-2.5; c statistic, 0.77). Higher ARS scores are associated with statistically significantly increased risk of anticholinergic adverse effects in older patients.
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            A drug burden index to define the functional burden of medications in older people.

            Older people carry a high burden of illness for which medications are indicated, along with increased risk of adverse drug reactions. We developed an index to determine drug burden based on pharmacologic principles. We evaluated the relationship of this index to physical and cognitive performance apart from disease indication. Data from the Health, Aging, and Body Composition Study on 3075 well-functioning community-dwelling persons aged 70 to 79 years were analyzed by multiple linear regression to assess the cross-sectional association of drug burden index with a validated composite continuous measure for physical function, and with the Digit Symbol Substitution Test for cognitive performance. Use of anticholinergic and sedative medications was associated with poorer physical performance score (anticholinergic exposure, 2.08 vs 2.21, P<.001; sedative exposure, 2.09 vs 2.19, P<.001) and cognitive performance on the Digit Symbol Substitution Test (anticholinergic exposure, 34.5 vs 35.5, P = .045; sedative exposure, 34.0 vs 35.5, P = .01). Associations were strengthened when exposure was calculated by principles of dose response. An increase of 1 U in drug burden index was associated with a deficit of 0.15 point (P<.001) on the physical function scale and 1.5 points (P = .01) on the Digit Symbol Substitution Test. These values were more than 3 times those associated with a single comorbid illness. The drug burden index demonstrates that anticholinergic and sedative drug exposure is associated with poorer function in community-dwelling older people. This pharmacologic approach provides a useful evidence-based tool for assessing the functional effect of exposure to medications in this population.
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              The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity.

              Anticholinergic Drug Scale (ADS) scores were previously associated with serum anticholinergic activity (SAA) in a pilot study. To replicate these results, the association between ADS scores and SAA was determined using simple linear regression in subjects from a study of delirium in 201 long-term care facility residents who were not included in the pilot study. Simple and multiple linear regression models were then used to determine whether the ADS could be modified to more effectively predict SAA in all 297 subjects. In the replication analysis, ADS scores were significantly associated with SAA (R2 = .0947, P < .0001). In the modification analysis, each model significantly predicted SAA, including ADS scores (R2 = .0741, P < .0001). The modifications examined did not appear useful in optimizing the ADS. This study replicated findings on the association of the ADS with SAA. Future work will determine whether the ADS is clinically useful for preventing anticholinergic adverse effects.
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                Author and article information

                Contributors
                00 31 50 36 38 49 6 , h.wouters@rug.nl
                Journal
                Eur J Clin Pharmacol
                Eur. J. Clin. Pharmacol
                European Journal of Clinical Pharmacology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0031-6970
                1432-1041
                1 December 2016
                1 December 2016
                2017
                : 73
                : 3
                : 257-266
                Affiliations
                ISNI 0000 0004 0407 1981, GRID grid.4830.f, Department of PharmacoTherapy, -Epidemiology & -Economics [PTEE], Groningen Research Institute of Pharmacy, Faculty of Mathematics and Natural Sciences, , University of Groningen, ; Antonius Deusinglaan 1, 9713 AV Groningen, Netherlands
                Article
                2162
                10.1007/s00228-016-2162-6
                5306241
                27909739
                f9666cdb-7f1a-4942-8a9b-285d04fe6fb0
                © The Author(s) 2016

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 21 September 2016
                : 10 November 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001826, ZonMw;
                Award ID: 80-83600-98-10176
                Award Recipient :
                Funded by: Stichting Stoffels-Hornstra
                Categories
                Review
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2017

                Pharmacology & Pharmaceutical medicine
                antimuscarinic agents,hypnotics and sedatives,polypharmacy,older adults, frailty,inappropriate prescribing

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