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BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available BMJ Open: first published as 10.1136/bmjopen-2019-029221 on 4 September 2019. Downloaded from http://bmjopen.bmj.com/ on September 26, 2021 by guest. Protected by copyright. responses online. online. responses ). ). http://bmjopen.bmj.com email please process review peer open BMJ Open’s on any questions If you have [email protected] BMJ Open is committed to open peer review. As part of this commitment we make the peer review review peer the make we commitment of this As part review. open peer to committed is Open BMJ available. publicly publish we article every of history authors’ the and comments reviewers’ the peer we post published is an article When that versions the are These peer review. during used were that paper of the versions the post We also to. apply comments review the peer review the peer during submitted that were versions the are follow that paper of the The versions or cited be not should They versions. published final or the of record versions the not are They process. manuscript. of this version published as the distributed of of record version author-corrected and typeset final, the full, journal and open access an is Open BMJ fees pay-per-view or charges subscription controls, access with no site on our available is manuscript the ( BMJ Open BMJ Open: first published as 10.1136/bmjopen-2019-029221 on 4 September 2019. Downloaded from An analysis of anticholinergic and sedative medicine effects on medicine-induced deterioration and frailty: a cross- sectional study ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-029221 Article Type: Research Date Submitted by the 17-Jan-2019 Author: Complete List of Authors: Lim, Renly; University of South Australia Division of Health Sciences, Quality Use of Medicines and Pharmacy Research Centre; University of South Australia Kalisch Ellett, Lisa; University of South Australia, Sansom Institute for Health Resarch, School of Pharmacy and Medical Sciences, Quality Use of Medicines and Pharmacy Research Centre Widadgo, Imaina; University of South Australia, Sansom Institute for Health Resarch, School of Pharmacy and Medical Sciences, Quality Use of Medicines and Pharmacy Research Centre Pratt, Nicole; University of South Australia, Sansom Institute for Health Resarch Roughead, Elizabeth; University of South Australia, Sansom Institute for Health Research http://bmjopen.bmj.com/ Keywords: anticholinergics, frail older adults, sedatives on September 26, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 26 BMJ Open 1 2 3 Title: An analysis of anticholinergic and sedative medicine effects on medicine-induced BMJ Open: first published as 10.1136/bmjopen-2019-029221 on 4 September 2019. Downloaded from 4 5 6 deterioration and frailty: a cross-sectional study 7 8 9 10 Author names and institution: 11 12 Renly Lim1, PhD, Lisa M. Kalisch Ellett1, PhD, Imaina S. Widagdo1, PhD, Nicole L. Pratt1, 13 14 15 PhD, Elizabeth E. Roughead1, PhD 16 17 18 For peer review only 19 1 Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical 20 21 22 Sciences, University of South Australia, Adelaide, Australia. 23 24 25 26 Corresponding author 27 28 29 Renly Lim 30 31 Quality Use of Medicines and Pharmacy Research Centre, 32 33 School of Pharmacy and Medical Sciences, 34 35 University of South Australia, 36 37 http://bmjopen.bmj.com/ 38 GPO Box 2471, Adelaide, SA 5001, Australia. 39 40 E-mail: [email protected] 41 42 Tel: +(61) 883 022 307 43 44 Fax: +(61) 8 8302 2466 45 on September 26, 2021 by guest. Protected copyright. 46 47 ORCID ID: https://orcid.org/0000-0003-4135-2523 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 26 2 1 2 3 Abstract BMJ Open: first published as 10.1136/bmjopen-2019-029221 on 4 September 2019. Downloaded from 4 5 6 7 Objective 8 To test the association between use of medicines with anticholinergic or sedative properties 9 10 and medicine-induced deterioration (physical function, cognitive function, appetite), and 11 12 frailty. 13 14 15 Design, setting and participants 16 17 This cross-sectional study analysed baseline data collected as part of the Australian 18 For peer review only 19 Longitudinal Study of Ageing (ALSA), a population based cohort of 2087 participants aged 20 21 65 years or over living in South Australia. 22 23 24 Main outcome measures 25 26 Physical function was measured at baseline using measures including hand grip strength, 27 walking speed, chair stands, activities of daily living (ADL), instrumental activities of daily 28 29 living (IADL). Cognitive function was measured using Mini Mental State Examination 30 31 (MMSE). Appetite was measured using Center for Epidemiologic Studies Depression (CES- 32 33 D) question 2. Frailty was measured using Frailty Index. The association between use of 34 anticholinergics or sedatives and physical or cognitive function, appetite, or frailty, was 35 36 assessed using analysis of covariance and ordinal or binary logistic regression. 37 http://bmjopen.bmj.com/ 38 39 40 Results 41 Almost half of the population were using anticholinergics or sedatives (n=954, 45.7%). Use 42 43 of anticholinergics was significantly associated with poorer grip strength (women only), 44 slower walking speed, poorer instrumental activities of daily living (IADL) and poorer 45 on September 26, 2021 by guest. Protected copyright. 46 appetite. Use of sedatives was significantly associated with poorer grip strength (men only), 47 48 slower walking speed and poorer IADL. We found no significant association between 49 50 medicine use and cognitive function. Users of anticholinergics or sedatives were significantly 51 52 more likely to be frail compared with non-users. 53 54 55 Conclusion 56 57 Use of medicines with anticholinergic or sedative properties is significantly associated with 58 medicine-induced deterioration (physical function and appetite) and frailty. Early 59 60 identification of signs and symptoms of medicine-induced deterioration is particularly For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 26 BMJ Open 3 1 2 3 important in older people so that worsening frailty and subsequent adverse events are BMJ Open: first published as 10.1136/bmjopen-2019-029221 on 4 September 2019. Downloaded from 4 5 prevented. 6 7 8 Keywords: anticholinergics; frail older adults; sedatives 9 10 11 12 Word count: 2905 13 14 15 16 17 Article Summary 18 For peer review only 19 Strengths and limitations of this study 20 21 Our findings on the association between use of anticholinergics and poorer appetite 22 contribute uniquely to the literature. 23 24 We analysed the association between medicines with anticholinergic or sedative 25 26 properties and grip strength based on gender, which previous studies have not done. 27 28 The study is limited by its cross-sectional design. It is not possible to identify a cause- 29 effect relationship between use of medicines with anticholinergic or sedative 30 31 properties and reduced physical function or poorer appetite using this study design. 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on September 26, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 26 4 1 2 3 Introduction BMJ Open: first published as 10.1136/bmjopen-2019-029221 on 4 September 2019. Downloaded from 4 5 Medicines with anticholinergic or sedative properties are commonly prescribed to older 6 7 people (1), with prevalence estimates ranging from 13 to 42% for medicines with sedative 8 properties (2, 3) and from 8 to 36% for medicines with anticholinergic properties (3, 4). 9 10 Adverse effects of these medicines, like falls and confusion are detrimental to older people. 11 12 This risk is increased due to age-related changes in pharmacokinetics and 13 14 pharmacodynamics, the presence of multiple co-morbidities and the use of multiple 15 medicines with subsequent increased probability of drug interactions (5, 6). The cumulative 16 17 medication burden of anticholinergic and sedative medicines is often unintentional and 18 For peer review only 19 compounded by the fact that many medicines with anticholinergic properties also have 20 21 sedative properties (5). 22 23 24 Use of medicines with anticholinergic or sedative properties can directly lead to adverse 25 26 events (5) which are easily recognised and potentially rectifiable. Use of medicines with 27 anticholinergic or sedative properties has also been associated with frailty (7), and frailty may 28 29 contribute to an increased risk of adverse events (8). However, medicines with 30 31 anticholinergic or sedative properties often have what might be considered “minor side 32 33 effects” which are difficult to detect and frequently unrecognised. These side effects, which 34 we describe as medicine-induced deterioration, particularly if the cumulative effect builds 35 36 slowly over time, is often misattributed as geriatric syndromes, frailty or simply changes due 37 http://bmjopen.bmj.com/ 38 to aging. Medicine-induced deterioration may include decline in physical function, decline in 39 40 cognitive function and loss of appetite. While these same symptoms may occur independently 41 due to aging, medicines with anticholinergic or sedative properties have side effect profiles 42 43 that also contribute to these declines. The lack of recognition of these signs and symptoms as 44 medicine-induced may subsequently contribute to increased risk of frailty and subsequent 45 on September 26, 2021 by guest.
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