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Harry Wu,1 Lisa Kouladjian O’Donnell,1 Kenji Fujita,1 Nashwa Masnoon,1,2 Sarah N Hilmer1 1Departments of Clinical Pharmacology and Aged Care, Faculty of Medicine and Health, The University of Sydney, Kolling Institute, Royal North Shore Hospital, Sydney, NSW, Australia; 2Department of Pharmacy, Royal North Shore Hospital, St Leonards, NSW, AustraliaCorrespondence: Sarah N HilmerLevel 13, Kolling Institute of Medical Research, Royal North Shore Hospital, Reserve Road, St Leonards, NSW, 2065, AustraliaTel +612 9926 4481Email sarah.hilmer@sydney.edu.auAbstract: Polypharmacy is a major challenge in healthcare for older people, and is associated with increased risks of adverse outcomes, such as delirium, falls, frailty, cognitive impairment and hospitalization. There is significant public and professional interest in the role of deprescribing in reducing medication-related harms in older people. We aim to provide a narrative review of 1) the safety and efficacy of deprescribing interventions, 2) the challenges and solutions of deprescribing research and implementation in clinical practice, and 3) the benefits of using Computerized Clinical Decision Support Systems (CCDSS) and Quality Indicators (QIs) in deprescribing research and practice. Deprescribing is an established management strategy to minimize polypharmacy and potentially inappropriate medications. There is limited clinical evidence for its efficacy on global and geriatric outcomes. Various challenges at patient, healthcare professional and healthcare system levels may impact on the success of deprescribing interventions in research and practice. Management strategies that target all levels of the healthcare system are required to overcome these challenges. Future studies may consider large multicenter prospective designs to establish the effects and sustainability of deprescribing interventions on clinical outcomes.Keywords: deprescribing, polypharmacy, geriatric, older people, computerized clinical decision support, quality indicator

Background: Polypharmacy has been associated with increased mortality but the contribution of different medication-related factors to this is unknown. Aims: The aim of this study was to identify demographic and medication-related predictors of mortality in the older population. Given the intrinsic link between polypharmacy and multimorbidity, the secondary aim was to examine if the medicines or underlying diseases predicted mortality. Methods: Patients aged ≥ 65 years from an outpatient multimorbidity clinic were included. Medication-related factors included the medicines count, high-risk medicines, inappropriate medicines duplication, and potential drug–drug and drug–disease interactions. Logistic regression was used to identify mortality predictors within a year of clinic discharge from the outpatient clinic. Patients attend the clinic until medications and comorbidity management have been optimised, at which point they are discharged from the clinic, and their General Practitioner provides ongoing care. Results: A total of 584 patients were included (median age 80.0 years) and 9.9% (n = 58) died within a year of discharge. Demographics, namely age (adjusted odds ratio [aOR] 1.05; 95% CI 1.01–1.09; p = 0.018) and being male (aOR 5.10; 95% CI 2.63–9.88; p < 0.001); chronic disease, namely heart failure (aOR 3.36; 95% CI 1.78–6.35; p < 0.001); and medication-related factors, namely the number of sedative and anticholinergic medicines (aOR 1.66; 95% CI 1.19–2.33; p = 0.003) predicted mortality in the study population. Conclusion: Whilst polypharmacy has been defined using the number of medicines in the literature, a combination of demographics, chronic disease and medications predicted mortality in our study. This provides guidance for the development of future tools and guidelines regarding the inclusion of key factors for identifying high-risk patients at risk of adverse health outcomes such as mortality. Refereed/Peer-reviewed

Objective: To identify demographic and medication-related predictors of unplanned hospitalisation and combine them into a hospitalisation risk score.Methods: Patients aged ≥65 years from an outpatient multimorbidity clinic were included. Hospitalisation predictors within a year of clinic discharge were identified using logistic regression. A risk score was developed. The area under the curve(AUC) was used to assess its predictive ability, compared to that of the medicines count (definition of polypharmacy). Results: A total of 598 patients were included (median age of 80.0 years). 58.0%(n = 347) were hospitalised within a year of clinic discharge. The AUC for the risk score incorporating age, medicines count, heart failure (HF), atherosclerotic disease and systemic steroids was 0.67 [95% CI 0.62-0.71], compared to 0.62 [95% CI 0.58-0.67] for the medicines count. Conclusion: A hospitalisation risk score incorporating demographics, medicines,namely steroids, and diseases such as HF had increased predictive ability compared to the medicines count, providing guidance for developing future polypharmacy tools. Refereed/Peer-reviewed

Background: In the literature, polypharmacy is commonly defined as using five or more medicines. Little is known about how physicians and pharmacists define and assess polypharmacy in practice.Aim: This study determined how expert physicians and pharmacists define and assess polypharmacy in practice.Methods: An online survey was sent to 25 expert physicians and pharmacists who were chosen if they had done significant work in the area of polypharmacy through major research, clinical practice or both, to identify how experts define and assess polypharmacyin practice. Results: Twenty-two participants completed the survey (88% response rate). There was strong agreement between experts, including which factors are important when assessing polypharmacy (intraclass correlation coefficient = 0.94). Respondents used the numberof medicines (n = 18 respondents; 56.3% of all definitions), such as five or more medicines, and brief descriptions (n = 4 respondents;43.7% of all definitions), such as assessing appropriateness given comorbidities, to define polypharmacy. Respondents commonly indicated patient factors such as functional status (n = 11 respondents; 50%) and medicine-related factors such as drug-drug interactions(n = 11; 50%) as important when assessing polypharmacy. Experts reported low use of externally validated polypharmacy tools during polypharmacy assessment, with 36.4% (n = 8) being unfamiliar with or never or rarely using these tools.Conclusion: Medication- and patient-related factors beyond a medicines count were deemed important in assessing polypharmacy. Given the low use of externally validated polypharmacy tools, strategies that include important medication- and patient-related factors are required to facilitate polypharmacy rationalisation. Refereed/Peer-reviewed

Background: This systematic review aims to summarise available patient-reported questionnaires to detect adverse drug reactions (ADRs) that can be utilised by healthcare professionals in clinical practice and to summarise the psychometric properties (validity, reliability, and responsiveness) of the questionnaires. Methods: A systematic literature search was conducted using Medline, Pubmed, Embase, and Emcare databases to screen for articles published between January 2000 and July 2020. Data items regarding validity, reliability, and responsiveness were extracted independently by two authors. The methodological quality was assessed using the COSMIN (Consensus-Based Standards for the Selection of Health Measurement Instruments) checklist. Results: A total of 1563 unique article titles were identified after removing duplicates. Following shortlisting of relevant articles, 19 patient-reported ADR questionnaires were identified. Questionnaires most commonly focused on mental health medications (42.1%, n = 8), followed by general questionnaires applicable to any medication (21.1%, n = 4). Many questionnaires did not report assessing the validity and reliability of the measurement tool. For example, only 11 questionnaires (58%) mentioned assessing content validity, in addition to criterion or construct testing. Conclusion: This systematic review summarised the available patient-reported questionnaires that can be used in research and clinical practice to identify ADRs. Results of this systematic review highlight the need for more robust validity and reliability testing when developing patient-reported ADR questionnaires. Refereed/Peer-reviewed

Background: There are tools and criteria in the literature aimed at distinguishing between appropriate and inappropriate medicines use. However, many have not been externally validated with regard to patient-related outcomes, potentially limiting their use in clinical practice. Objectives: The aim of the study was to conduct a systematic review to summarise (1) available prescribing appropriateness assessment tools and criteria, and (2) their associations with patient-related outcomes (external validity). Methods: A systematic review was conducted using MEDLINE, EMBASE and Informit (Health Collection) databases to screen for articles in English that examined (1) tools to assess the appropriateness of prescribing and (2) associations of tools with patient-related outcomes, published between 2000 and 2016, without any limits placed on the study design, participant age or setting. Results: After screening 1710 articles, removing duplicates and shortlisting relevant articles, 42 prescribing assessment tools were identified. Out of the 42 tools, 78.6% (n = 33) provided guidance around stopping inappropriate medications, 28.6% (n = 12) around starting appropriate medications, 61.9% (n = 26) were explicit (criteria based) and 31.0% (n = 13) had been externally validated, with hospitalisation being the most commonly used patient-related outcome (n = 9, 21.4%). Conclusion: The results of this systematic review highlight the need for evidence-based and externally validated tools, which combine the different aspects of medication management to optimise patient-related outcomes. PROSPERO registration number: CRD42017067233. Refereed/Peer-reviewed

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. Refereed/Peer-reviewed

Background: Patient education delivered through pharmacist counselling is important in promoting the safe and effective use of anticoagulants. Aim: To evaluate the extent to which patients retain information after counselling from a clinical pharmacist about the anticoagulant warfarin; to perform a brief analysis of the cost-analysis of warfarin counselling; and to investigate relationships between case-specific characteristics and patient outcomes. Method: A total of 22 patients was recruited. Eligibility criteria included age ≥18 years, new initiation of warfarin in hospital, intact cognition and an expectation of self-administration of warfarin after discharge. Key elements of knowledge were assessed immediately after counselling and 6 weeks after counselling. The duration of each counselling session was recorded as a surrogate for costs involved, and case-specific characteristics were documented. Results: Participants demonstrated an ability to recall an average (mean standard deviation) of 79.9 14.6% of key information elements immediately after counselling, significantly higher than was observed 6 weeks after counselling (71.0 11.7%; p = 0.02). The percentage of participants achieving an ‘acceptable’ score for knowledge was 68.2%, both immediately after counselling and 6 weeks later. No significant relationships between specific case characteristics and patient outcomes, duration of counselling or overall warfarin knowledge retention scores 6 weeks after counselling were demonstrable. Conclusion: These findings imply that more emphasis should be placed on educating patients on the critical information elements for warfarin counselling. Further research is required to explore potential relationships between case-specific characteristics and patient outcomes, as well as the costs associated with the counselling process. Refereed/Peer-reviewed