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Published in: International Journal of Clinical Pharmacy 1/2021

01-02-2021 | Research Article

Size of the associations between anticholinergic burden tool scores and adverse outcomes in older patients

Authors: Marta Lavrador, Ana C. Cabral, Isabel V. Figueiredo, Manuel T. Veríssimo, M. Margarida Castel-Branco, Fernando Fernandez-Llimos

Published in: International Journal of Clinical Pharmacy | Issue 1/2021

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Abstract

Background Several anticholinergic scales and equations to evaluate the anticholinergic burden have been previously created. Association of these instruments with the anticholinergic outcomes are usually estimated by means of hypothesis contrast tests, which ignore the size of the association effect. Objective To evaluate the effect size of the associations between the scores on cumulative anticholinergic burden instruments with peripheral or central anticholinergic adverse outcomes in older patients. Setting Internal medicine ward of a Tertiary University Hospital. Methods A case–control study was conducted in patients over 65 years who were admitted to two internal medicine wards of a Portuguese university hospital. The Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden scale and Drug Burden Index were used to calculate the patients’ anticholinergic burden. Peripheral (dry mouth—swab technique; dry eye—Schirmer test) and central (falls and cognitive impairment—Mini-Mental State Examination) anticholinergic adverse outcomes were investigated. The Barthel Index was used to assess overall physical functionality. The Mann–Whitney test was used to evaluate probabilistic differences in the anticholinergic scores between case and control individuals. To establish the effect size of the associations, the area under the curve of the receiver operating characteristics curve was calculated. Main outcome measure Anticholinergic adverse effects. Results A total of 250 patients (mean age 81.67 years, standard deviation 7.768; 50% females) were included. In total, 148 patients (59.2%) presented with dry mouth, 85 (34%) with dry eye, 141 (56.4%) with impaired functionality, 44 (17.6%) with a history of falls and 219 (87.6%) with cognitive impairment. Significant differences (p < 0.05) were obtained for the majority of the associations between Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden and Drug Burden Index and adverse effects. Conversely, the effect sizes of these associations ranged from “fail” (area under the curve 0.5 to 0.6) to “fair” (area under the curve 0.7 to 0.8). Conclusion Although significant differences in the scores of anticholinergic burden instruments and adverse outcomes may exist, the effect sizes of these associations ranged from ‘fail’ to ‘fair’, which limits their utility in preventing anticholinergic adverse outcomes with medication review interventions.
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Literature
1.
go back to reference Naples JG, Marcum ZA, Perera S, Gray SL, Newman AB, Simonsick EM, et al. Concordance between anticholinergic burden scales. J Am Geriatr Soc. 2015;63:2120–4.PubMedPubMedCentral Naples JG, Marcum ZA, Perera S, Gray SL, Newman AB, Simonsick EM, et al. Concordance between anticholinergic burden scales. J Am Geriatr Soc. 2015;63:2120–4.PubMedPubMedCentral
2.
go back to reference Nishtala PS, Salahudeen MS, Hilmer SN. Anticholinergics: theoretical and clinical overview. Expert Opin Drug Saf. 2016;15:753–68.PubMed Nishtala PS, Salahudeen MS, Hilmer SN. Anticholinergics: theoretical and clinical overview. Expert Opin Drug Saf. 2016;15:753–68.PubMed
3.
go back to reference Duran CE, Azermai M, Vander Stichele RH. Systematic review of anticholinergic risk scales in older adults. Eur J Clin Pharmacol. 2013;69:1485–96.PubMed Duran CE, Azermai M, Vander Stichele RH. Systematic review of anticholinergic risk scales in older adults. Eur J Clin Pharmacol. 2013;69:1485–96.PubMed
4.
go back to reference Salahudeen MS, Duffull SB, Nishtala PS. Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review. BMC Geriatr. 2015;15:31.PubMedPubMedCentral Salahudeen MS, Duffull SB, Nishtala PS. Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review. BMC Geriatr. 2015;15:31.PubMedPubMedCentral
5.
go back to reference Mayer T, Haefeli WE, Seidling HM. Different methods, different results—How do available methods link a patient’s anticholinergic load with adverse outcomes? Eur J Clin Pharmacol. 2015;71:1299–314.PubMed Mayer T, Haefeli WE, Seidling HM. Different methods, different results—How do available methods link a patient’s anticholinergic load with adverse outcomes? Eur J Clin Pharmacol. 2015;71:1299–314.PubMed
6.
go back to reference Villalba-Moreno AM, Alfaro-Lara ER, Perez-Guerrero MC, Nieto-Martin MD, Santos-Ramos B. Systematic review on the use of anticholinergic scales in poly pathological patients. Arch Gerontol Geriatr. 2016;62:1–8.PubMed Villalba-Moreno AM, Alfaro-Lara ER, Perez-Guerrero MC, Nieto-Martin MD, Santos-Ramos B. Systematic review on the use of anticholinergic scales in poly pathological patients. Arch Gerontol Geriatr. 2016;62:1–8.PubMed
7.
go back to reference Kersten H, Wyller TB. Anticholinergic drug burden in older people’s brain—How well is it measured? Basic Clin Pharmacol Toxicol. 2014;114:151–9.PubMed Kersten H, Wyller TB. Anticholinergic drug burden in older people’s brain—How well is it measured? Basic Clin Pharmacol Toxicol. 2014;114:151–9.PubMed
8.
go back to reference Rudd KM, Raehl CL, Bond CA, Abbruscato TJ, Stenhouse AC. Methods for assessing drug-related anticholinergic activity. Pharmacotherapy. 2005;25:1592–601.PubMed Rudd KM, Raehl CL, Bond CA, Abbruscato TJ, Stenhouse AC. Methods for assessing drug-related anticholinergic activity. Pharmacotherapy. 2005;25:1592–601.PubMed
9.
go back to reference Cardwell K, Hughes CM, Ryan C. The association between anticholinergic medication burden and health related outcomes in the ‘oldest old’: a systematic review of the literature. Drugs Aging. 2015;32:835–48.PubMed Cardwell K, Hughes CM, Ryan C. The association between anticholinergic medication burden and health related outcomes in the ‘oldest old’: a systematic review of the literature. Drugs Aging. 2015;32:835–48.PubMed
10.
go back to reference Welsh TJ, van der Wardt V, Ojo G, Gordon AL, Gladman JRF. Anticholinergic drug burden tools/scales and adverse outcomes in different clinical settings: a systematic review of reviews. Drugs Aging. 2018;35:523–38.PubMed Welsh TJ, van der Wardt V, Ojo G, Gordon AL, Gladman JRF. Anticholinergic drug burden tools/scales and adverse outcomes in different clinical settings: a systematic review of reviews. Drugs Aging. 2018;35:523–38.PubMed
11.
12.
go back to reference Oliveira J, Cabral AC, Lavrador M, Costa FA, Almeida FF, Macedo A, et al. Contribution of different patient information sources to create the best possible medication history. Acta Med Port. 2020;33:384–9.PubMed Oliveira J, Cabral AC, Lavrador M, Costa FA, Almeida FF, Macedo A, et al. Contribution of different patient information sources to create the best possible medication history. Acta Med Port. 2020;33:384–9.PubMed
13.
go back to reference Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168:508–13.PubMed Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168:508–13.PubMed
14.
go back to reference Carnahan RM, Lund BC, Perry PJ, Pollock BG, Culp KR. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol. 2006;46:1481–6.PubMed Carnahan RM, Lund BC, Perry PJ, Pollock BG, Culp KR. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol. 2006;46:1481–6.PubMed
15.
go back to reference Campbell NL, Maidment I, Fox C, Khan B, Boustani M. The 2012 Update to the Anticholinergic Cognitive Burden Scale. J Am Geriatr Soc. 2013;61:S142–3. Campbell NL, Maidment I, Fox C, Khan B, Boustani M. The 2012 Update to the Anticholinergic Cognitive Burden Scale. J Am Geriatr Soc. 2013;61:S142–3.
16.
go back to reference Hilmer SN, Mager DE, Simonsick EM, Cao Y, Ling SM, Windham BG, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med. 2007;167:781–7.PubMed Hilmer SN, Mager DE, Simonsick EM, Cao Y, Ling SM, Windham BG, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med. 2007;167:781–7.PubMed
17.
go back to reference Hilmer SN, Mager DE, Simonsick EM, Ling SM, Windham BG, Harris TB, et al. Drug burden index score and functional decline in older people. Am J Med. 2009;122(1142–9):e1–2. Hilmer SN, Mager DE, Simonsick EM, Ling SM, Windham BG, Harris TB, et al. Drug burden index score and functional decline in older people. Am J Med. 2009;122(1142–9):e1–2.
18.
go back to reference O’Connell J, Burke E, Mulryan N, O’Dwyer C, Donegan C, McCallion P, et al. Drug burden index to define the burden of medicines in older adults with intellectual disabilities: an observational cross-sectional study. Br J Clin Pharmacol. 2018;84:553–67.PubMedPubMedCentral O’Connell J, Burke E, Mulryan N, O’Dwyer C, Donegan C, McCallion P, et al. Drug burden index to define the burden of medicines in older adults with intellectual disabilities: an observational cross-sectional study. Br J Clin Pharmacol. 2018;84:553–67.PubMedPubMedCentral
19.
go back to reference Gnjidic D, Bell JS, Hilmer SN, Lonnroos E, Sulkava R, Hartikainen S. Drug Burden Index associated with function in community-dwelling older people in Finland: a cross-sectional study. Ann Med. 2012;44:458–67.PubMed Gnjidic D, Bell JS, Hilmer SN, Lonnroos E, Sulkava R, Hartikainen S. Drug Burden Index associated with function in community-dwelling older people in Finland: a cross-sectional study. Ann Med. 2012;44:458–67.PubMed
20.
go back to reference Kersten H, Molden E, Tolo IK, Skovlund E, Engedal K, Wyller TB. Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: a randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2013;68:271–8.PubMed Kersten H, Molden E, Tolo IK, Skovlund E, Engedal K, Wyller TB. Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: a randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2013;68:271–8.PubMed
21.
go back to reference Jongerius PH, van Limbeek J, Rotteveel JJ. Assessment of salivary flow rate: biologic variation and measure error. Laryngoscope. 2004;114:1801–4.PubMed Jongerius PH, van Limbeek J, Rotteveel JJ. Assessment of salivary flow rate: biologic variation and measure error. Laryngoscope. 2004;114:1801–4.PubMed
22.
go back to reference Lofgren CD, Wickstrom C, Sonesson M, Lagunas PT, Christersson C. A systematic review of methods to diagnose oral dryness and salivary gland function. BMC Oral Health. 2012;12:29.PubMedPubMedCentral Lofgren CD, Wickstrom C, Sonesson M, Lagunas PT, Christersson C. A systematic review of methods to diagnose oral dryness and salivary gland function. BMC Oral Health. 2012;12:29.PubMedPubMedCentral
24.
go back to reference Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J. 1965;14:61–5.PubMed Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J. 1965;14:61–5.PubMed
25.
go back to reference Pasina L, Djade CD, Lucca U, Nobili A, Tettamanti M, Franchi C, et al. Association of anticholinergic burden with cognitive and functional status in a cohort of hospitalized elderly: comparison of the anticholinergic cognitive burden scale and anticholinergic risk scale: results from the REPOSI study. Drugs Aging. 2013;30:103–12.PubMed Pasina L, Djade CD, Lucca U, Nobili A, Tettamanti M, Franchi C, et al. Association of anticholinergic burden with cognitive and functional status in a cohort of hospitalized elderly: comparison of the anticholinergic cognitive burden scale and anticholinergic risk scale: results from the REPOSI study. Drugs Aging. 2013;30:103–12.PubMed
26.
go back to reference Folstein MF, Folstein SE, McHugh PR. Mini-mental state A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.PubMed Folstein MF, Folstein SE, McHugh PR. Mini-mental state A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.PubMed
27.
go back to reference Gnjidic D, Cumming RG, Le Couteur DG, Handelsman DJ, Naganathan V, Abernethy DR, et al. Drug Burden Index and physical function in older Australian men. Br J Clin Pharmacol. 2009;68:97–105.PubMedPubMedCentral Gnjidic D, Cumming RG, Le Couteur DG, Handelsman DJ, Naganathan V, Abernethy DR, et al. Drug Burden Index and physical function in older Australian men. Br J Clin Pharmacol. 2009;68:97–105.PubMedPubMedCentral
28.
go back to reference Fritz CO, Morris PE, Richler JJ. Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen. 2012;141:2–18.PubMed Fritz CO, Morris PE, Richler JJ. Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen. 2012;141:2–18.PubMed
29.
go back to reference Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Mahwah: Lawrence Erlbaum; 1988. Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Mahwah: Lawrence Erlbaum; 1988.
30.
go back to reference Hajian-Tilaki K. Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Caspian J Intern Med. 2013;4:627–35.PubMedPubMedCentral Hajian-Tilaki K. Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Caspian J Intern Med. 2013;4:627–35.PubMedPubMedCentral
32.
go back to reference Millsop JW, Wang EA, Fazel N. Etiology, evaluation, and management of xerostomia. Clin Dermatol. 2017;35:468–76.PubMed Millsop JW, Wang EA, Fazel N. Etiology, evaluation, and management of xerostomia. Clin Dermatol. 2017;35:468–76.PubMed
33.
go back to reference Schreiber JB. New paradigms for considering statistical significance: a way forward for health services research journals, their authors, and their readership. Res Soc Adm Pharm. 2019;16:591–4. Schreiber JB. New paradigms for considering statistical significance: a way forward for health services research journals, their authors, and their readership. Res Soc Adm Pharm. 2019;16:591–4.
34.
go back to reference Wasserstein RL, Lazar NA. The ASA statement on p-values: context, process, and purpose. The American Statistician. 2016;70:129–33. Wasserstein RL, Lazar NA. The ASA statement on p-values: context, process, and purpose. The American Statistician. 2016;70:129–33.
35.
go back to reference Kersten H, Molden E, Willumsen T, Engedal K, Bruun WT. Higher anticholinergic drug scale (ADS) scores are associated with peripheral but not cognitive markers of cholinergic blockade. cross sectional data from 21 Norwegian nursing homes. Br J Clin Pharmacol. 2013;75:842–9.PubMedPubMedCentral Kersten H, Molden E, Willumsen T, Engedal K, Bruun WT. Higher anticholinergic drug scale (ADS) scores are associated with peripheral but not cognitive markers of cholinergic blockade. cross sectional data from 21 Norwegian nursing homes. Br J Clin Pharmacol. 2013;75:842–9.PubMedPubMedCentral
36.
go back to reference Wouters H, van der Meer H, Taxis K. Quantification of anticholinergic and sedative drug load with the Drug Burden Index: a review of outcomes and methodological quality of studies. Eur J Clin Pharmacol. 2017;73:257–66.PubMed Wouters H, van der Meer H, Taxis K. Quantification of anticholinergic and sedative drug load with the Drug Burden Index: a review of outcomes and methodological quality of studies. Eur J Clin Pharmacol. 2017;73:257–66.PubMed
37.
go back to reference Whalley LJ, Sharma S, Fox HC, Murray AD, Staff RT, Duthie AC, et al. Anticholinergic drugs in late life: adverse effects on cognition but not on progress to dementia. J Alzheimers Dis. 2012;30:253–61.PubMed Whalley LJ, Sharma S, Fox HC, Murray AD, Staff RT, Duthie AC, et al. Anticholinergic drugs in late life: adverse effects on cognition but not on progress to dementia. J Alzheimers Dis. 2012;30:253–61.PubMed
38.
go back to reference Boustani M, Campbell N, Munger S, Maidment I, Fox C. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008;4:311–20. Boustani M, Campbell N, Munger S, Maidment I, Fox C. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008;4:311–20.
39.
go back to reference Gnjidic D, Le Couteur DG, Naganathan V, Cumming RG, Creasey H, Waite LM, et al. Effects of drug burden index on cognitive function in older men. J Clin Psychopharmacol. 2012;32:273–7.PubMed Gnjidic D, Le Couteur DG, Naganathan V, Cumming RG, Creasey H, Waite LM, et al. Effects of drug burden index on cognitive function in older men. J Clin Psychopharmacol. 2012;32:273–7.PubMed
40.
go back to reference Bostock CV, Soiza RL, Mangoni AA. Associations between different measures of anticholinergic drug exposure and Barthel Index in older hospitalized patients. Therap Adv Drug Saf. 2013;4:235–45. Bostock CV, Soiza RL, Mangoni AA. Associations between different measures of anticholinergic drug exposure and Barthel Index in older hospitalized patients. Therap Adv Drug Saf. 2013;4:235–45.
41.
go back to reference Tan MP, Tan GJ, Mat S, Luben RN, Wareham NJ, Khaw KT, et al. Use of Medications with anticholinergic properties and the long-term risk of hospitalization for falls and fractures in the EPIC-Norfolk longitudinal cohort study. Drugs Aging. 2019;37:105–14. Tan MP, Tan GJ, Mat S, Luben RN, Wareham NJ, Khaw KT, et al. Use of Medications with anticholinergic properties and the long-term risk of hospitalization for falls and fractures in the EPIC-Norfolk longitudinal cohort study. Drugs Aging. 2019;37:105–14.
42.
go back to reference Salahudeen MS, Chyou TY, Nishtala PS. Serum anticholinergic activity and cognitive and functional adverse outcomes in older people: a systematic review and meta-analysis of the literature. PLoS ONE. 2016;11:e0151084.PubMedPubMedCentral Salahudeen MS, Chyou TY, Nishtala PS. Serum anticholinergic activity and cognitive and functional adverse outcomes in older people: a systematic review and meta-analysis of the literature. PLoS ONE. 2016;11:e0151084.PubMedPubMedCentral
43.
go back to reference Alba AC, Agoritsas T, Walsh M, Hanna S, Iorio A, Devereaux PJ. Discrimination and calibration of clinical prediction models: users’ guides to the medical literature. JAMA. 2017;318:1377–84.PubMed Alba AC, Agoritsas T, Walsh M, Hanna S, Iorio A, Devereaux PJ. Discrimination and calibration of clinical prediction models: users’ guides to the medical literature. JAMA. 2017;318:1377–84.PubMed
44.
go back to reference Kaufmann CP, Tremp R, Hersberger KE, Lampert ML. Inappropriate prescribing: a systematic overview of published assessment tools. Eur J Clin Pharmacol. 2014;70:1–11.PubMed Kaufmann CP, Tremp R, Hersberger KE, Lampert ML. Inappropriate prescribing: a systematic overview of published assessment tools. Eur J Clin Pharmacol. 2014;70:1–11.PubMed
Metadata
Title
Size of the associations between anticholinergic burden tool scores and adverse outcomes in older patients
Authors
Marta Lavrador
Ana C. Cabral
Isabel V. Figueiredo
Manuel T. Veríssimo
M. Margarida Castel-Branco
Fernando Fernandez-Llimos
Publication date
01-02-2021
Publisher
Springer International Publishing
Published in
International Journal of Clinical Pharmacy / Issue 1/2021
Print ISSN: 2210-7703
Electronic ISSN: 2210-7711
DOI
https://doi.org/10.1007/s11096-020-01117-x

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