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Aim: To investigate the incidence of, and factors associated with addition and switching of glucose-lowering medications within 12-months of initiating metformin or a sulfonylurea for type 2 diabetes (T2D). Methods: We identified 109,573 individuals aged 18-99 years who initiated metformin or a sulfonylurea between July 2013 and April 2015 using Australian National Diabetes Service Scheme (NDSS) data linked with national dispensing data. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CI) for factors associated with time to addition to or switch from metformin or sulfonylurea over a 12-months follow-up. Results: Treatment addition or switching occurred in 18% and 4% of individuals who initiated metformin and in 28% and 13% of individuals who initiated sulfonylureas. Median time to addition was 104 days for metformin and 82 days for sulfonylureas. Median time to switching was 63 days for metformin and 52 days for sulfonylureas. Congestive heart failure, nicotine dependence, end stage renal disease and dispensing of systemic corticosteroids were associated with higher likelihood of treatment additions and switching in individuals initiating metformin. Antipsychotic dispensing was associated with a higher likelihood of treatment addition in individuals initiating sulfonylureas. Women initiating metformin were less likely to receive treatment additions but more likely to switch treatment than men. Conclusion: Nearly one quarter of Australians who initiate treatment for T2D with metformin or sulfonylureas switch or receive additional treatment within 12-months, with those who initiate sulfonylureas more likely to switch or receive additional treatment than those who initiate metformin., Competing Interests: JB has received grant income paid to his employer from NHMRC, Australian Government Department of Health, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, GSK Independent Medical Education and several aged care provider organizations. JI reports grants from AstraZeneca, Amgen, Dementia Australia Research Foundation, National Health and Medical Research Council, and National Breast Cancer Foundation, outside the submitted work. JES is supported by a National Health and Medical Research Council Investigator grant. JES reports personal fees from Astra Zeneca, Sanofi, Novo Nordisk, MSD, Eli Lilly, Pfizer, Mylan and Zuellig outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wood, Magliano, Bell, Shaw and Ilomäki.)

Frailty, dementia and complex multimorbidity are highly prevalent among residents of long-term care facilities (LTCFs). Prescribing for residents of LTCFs is often informed by disease-specific clinical practice guidelines based on research conducted among younger and more robust adults. However, frailty and cognitive impairment may modify medication benefits and risks. Residents with frailty and advanced dementia may be at increased susceptibility to adverse drug events (ADEs) and often have a lower likelihood of achieving long-term therapeutic benefit from chronic preventative medications. For this reason, there is a strong rationale for deprescribing, particularlyamong residents with high medication burdens, swallowing difficulties or limited dexterity. Conversely, frailty and dementia have also been associated with under-prescribing of clinically indicated medications. Unnecessarily withholding treatment based on assumed risk may deprive vulnerable population groups from receiving evidence-based care. There is a need for specific evidence regarding medication benefits and risks in LTCF residents with frailty and dementia. Observational studies conducted using routinely collected health data may complement evidence from randomized controlled trials that often exclude people living with dementia, frailty and in LTCFs. Balancing over- and under-prescribing requires consideration of each resident's frailty and cognitive status, therapeutic goals, time-to-benefit, potential ADEs, and individual values or preferences. Incorporating frailty screening into medication review may also provide better alignment of medication regimens to changing goals of care. Timely identification of frail residents as part of treatment decision-making may assist with targeting interventions to minimize and monitor for ADEs. Shifting away from rigid application of conventional disease-specific clinical practice guidelines may provide an individualized and more holistic assessment of medication benefits and risks in the LTCF setting.

Objective: To investigate the prevalence, outcomes, and factors associated with potential glycemic overtreatment and undertreatment of type 2 diabetes mellitus (T2DM) in long-term care facilities (LTCFs)., Design: Systematic review., Setting and Participants: Residents with T2DM and aged ≥60 years living in LTCFs., Measures: Articles published between January 2000 and September 2020 were retrieved following a systematic search of MEDLINE, EMBASE, Cochrane Library, CINAHL plus, and gray literature. Inclusion criteria were the reporting of (1) potential overtreatment and undertreatment quantitatively defined (implicitly or explicitly) based on hemoglobin A1c (HbA1c) and/or blood glucose; (2) prevalence, outcomes, and associated factors of potential glycemic overtreatment and undertreatment; and (3) the study involved residents of LTCFs., Results: Fifteen studies were included. Prevalence of potential overtreatment (5%-86%, n = 15 studies) and undertreatment (1.4%-35%, n = 8 studies) varied widely among facilities and geographical locations, and according to definitions used. Prevalence of potential overtreatment was 16%-74% when defined as treatment with a glucose-lowering medication in a resident with ≥1 hypoglycemia risk factor or serious comorbidity, together with a HbA1c <7% (n = 10 studies). Potential undertreatment was commonly defined as residents on glucose-lowering medication having HbA1c >8.5% and the prevalence 1.4%-14.8% (n = 6 studies). No studies prospectively measured resident health outcomes from overtreatment and undertreatment. Potential overtreatment was positively associated with use of oral glucose-lowering medications, dementia diagnosis or dementia severity, and/or need for assistance with activities of daily living (n = 2 studies). Negative association was found between potential overtreatment and use of insulin/combined insulin and oral glucose-lowering medication. No studies reported factors associated with potential undertreatment., Conclusions and Implications: The prevalence of potential glycemic overtreatment and undertreatment varied widely among residents with T2DM depending on the definition(s) used in each study. Longitudinal studies examining associations between glycemic management and health outcomes, and the use of consensus definitions of overtreatment and undertreatment are required to establish findings about actual glycemic overtreatment and undertreatment in LTCFs., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Electronic information systems are becoming increasingly common in residential aged care in Australia. These systems contain valuable data generated during day-to-day care delivery for older adults. These data (termed 'routinely collected residential aged care provider data') are currently underutilised, however have potential significant benefits for both care delivery and research purposes. Routinely collected residential aged care provider data are more readily accessible, contain up-to-date information and can be linked to existing national or state-based administrative data sets, while providing more granular details about care delivered at the coalface. The aim of this paper is to provide clinicians, researchers, policymakers and providers with an understanding of the strengths of these types of data, as well as identifying areas that require future development to maximise their potential to drive improvements in resident care and outcomes. These considerations include data quality, data standardisation and models for data governance, consent and consumer involvement., (© 2021 AJA Inc.)

Background: Venous thromboembolism (VTE) represents a rare but preventable postoperative complication. Unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) are used to prevent VTE, but comparative studies of their safety and efficacy in the neurosurgical context are limited., Objective: To determine the relative safety and efficacy of UH and LMWH for prophylaxis after cranial surgery., Methods: We performed a retrospective analysis of 3204 elective intracranial surgical admissions in 2901 patients over the period 2013 to 2018. From chart review, we extracted demographic and clinical features, including diagnosis and procedure, drugs administered, and the occurrence of VTE events. To compare postoperative outcomes, we performed propensity score matching of patients receiving different drugs, and reviewed postoperative cranial imaging. To contextualize our results, we selected 14 prior neurosurgical studies of VTE prophylaxis to compare our outcomes to the existing literature., Results: In our sample of 3204 admissions, the overall rate of VTE was 0.8% (n = 27). Rates of VTE were not statistically different in matched cohorts receiving UH and LMWH (1.7% vs 1.0%, respectively); however, LMWH was associated with a higher rate of clinically significant intracranial hemorrhage (ICH) (3.4% vs 0.5%, P = .008). Literature review and meta-analysis supported these findings. Across studies, UH and LMWH were associated with similar rates of VTE. Studies in which patients received LMWH reported significantly higher rates of ICH (4.9% higher, P = .005)., Conclusion: We find that LMWH and UH show similar efficacy in preventing VTE; however, LMWH is associated with higher rates of ICH., (© Congress of Neurological Surgeons 2021.)

Background: Little is known about changes in pro re nata (PRN) medication prescribing and administration in residential aged care facilities (RACFs) over time., Objective: To determine the prevalence and factors associated with PRN medication administration in RACFs and examine changes over 12-months., Methods: Secondary analyses utilizing data from the SIMPLER randomized controlled trial (n = 242 residents, 8 RACFs) was undertaken. PRN medication data were extracted from RACF medication charts. Factors associated with PRN medication administration in the preceding week were explored using multivariable logistic regression., Results: At baseline, 211 residents (87.2%) were prescribed ≥1 PRN medication, with 77 (36.5%) administered PRN medication in the preceding week. PRN administration was more likely in non-metropolitan areas, and less likely among residents with more severe dementia symptoms and greater dependence with activities of daily living. No significant differences in overall PRN prescribing or administration in 162 residents alive at 12-month follow-up were observed., Conclusions: Despite being frequently prescribed, the contribution of PRNs to overall medication use in RACFs is small. PRN prescribing and administration was relatively static over 12-months despite likely changes in resident health status over this period, suggesting further exploration of PRN prescribing in relation to resident care needs may be warranted., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Hip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records., Methods and Analysis: This retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported., Ethics and Dissemination: Each participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences., Competing Interests: Competing interests: ICKW, SW, KMCV, A-MT, HTS, J-YS, DP-A, MMdA, EC-CL, KK, CD-P, MC, AHYC, and JSB had financial support from Amgen Inc. for the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute kidney injury (AKI) is a recognised complication of coronavirus disease 2019 (COVID-19), yet the reported incidence varies widely and the associated risk factors are poorly understood., Methods: Data was collected on all adult patients who returned a positive COVID-19 swab while hospitalised at a large UK teaching hospital between 1st March 2020 and 3rd June 2020. Patients were stratified into community- and hospital-acquired AKI based on the timing of AKI onset., Results: Out of the 448 eligible patients with COVID-19, 118 (26.3 %) recorded an AKI during their admission. Significant independent risk factors for community-acquired AKI were chronic kidney disease (CKD), diabetes, clinical frailty score and admission C-reactive protein (CRP), systolic blood pressure and respiratory rate. Similar risk factors were significant for hospital-acquired AKI including CKD and trough systolic blood pressure, peak heart rate, peak CRP and trough lymphocytes during admission. In addition, invasive mechanical ventilation was the most significant risk factor for hospital-acquired AKI (adjusted odds ratio 9.1, p < 0.0001) while atrial fibrillation conferred a protective effect (adjusted odds ratio 0.29, p < 0.0209). Mortality was significantly higher for patients who had an AKI compared to those who didn't have an AKI (54.3 % vs. 29.4 % respectively, p < 0.0001). On Cox regression, hospital-acquired AKI was significantly associated with mortality (adjusted hazard ratio 4.64, p < 0.0001) while community-acquired AKI was not., Conclusions: AKI occurred in over a quarter of our hospitalised COVID-19 patients. Community- and hospital-acquired AKI have many shared risk factors which appear to converge on a pre-renal mechanism of injury. Hospital- but not community acquired AKI was a significant risk factor for death., (© 2021. The Author(s).)

Complex medication regimens are highly prevalent, burdensome for residents and staff, and associated with poor health outcomes in residential aged care facilities (RACFs). The SIMPLER study was a non-blinded, matched-pair, cluster randomized controlled trial in eight Australian RACFs that investigated the one-off application of a structured 5-step implicit process to simplify medication regimens. The aim of this study was to explore the processes underpinning study implementation and uptake of the medication simplification intervention. A mixed methods process evaluation with an explanatory design was undertaken in parallel with the main outcome evaluation of the SIMPLER study and was guided by an established 8-domain framework. The qualitative component included a document analysis and semi-structured interviews with 25 stakeholders (residents, family, research nurses, pharmacists, RACF staff, and a general medical practitioner). Interviews were transcribed verbatim and reflexively thematically content analyzed. Descriptive statistics were used to summarize quantitative data extracted from key research documents. The SIMPLER recruitment rates at the eight RACFs ranged from 18.9% to 48.6% of eligible residents (38.4% overall). Participation decisions were influenced by altruism, opinions of trusted persons, willingness to change a medication regimen, and third-party hesitation regarding potential resident distress. Intervention delivery was generally consistent with the study protocol. Stakeholders perceived regimen simplification was beneficial and low risk if the simplification recommendations were individualized. Implementation of the simplification recommendations varied between the four intervention RACFs, with simplification implemented at 4-month follow-up for between 25% and 86% of residents for whom simplification was possible. Good working relationships between stakeholders and new remunerated models of medication management were perceived facilitators to wider implementation. In conclusion, the one-off implicit medication simplification intervention was feasible and generally delivered according to the protocol to a representative sample of residents. Despite variable implementation, recommendations to simplify complex regimens were valued by stakeholders, who also supported wider implementation of medication simplification in RACFs.

Background: Medicine use is considered off-label when used for an indication, at a dose, via a route of administration or in a patient group not included in the approved product information. Off-label use varies according to therapeutic class and patient group, and often occurs in those who are vulnerable., Objective: The aim of this article is to discuss ethical, practice and policy considerations associated with off-label medicine use., Discussion: A number of professional organisations have issued guidance in relation to off-label medicine use. Prescribers should inform patients and document consent when prescribing off-label, including an open discussion about known and unknown benefits and risks. It is important that the prescriber documents the reason for off-label use in the patient's record and ensures that patients are aware of the intended duration and relevant monitoring. Australia's new national health priority of Quality Use of Medicine and Medicine Safety should stimulate all stakeholders including consumers to work together to address off-label medicine use.

Background: Use of physical and chemical restraints are common in residential aged care facilities worldwide. Restraint use can pose harm to residents even causing deaths., Objective: To synthesize the prevalence and variability in physical and chemical restraint use, and examine factors that may contribute to this variability of prevalence rates., Methods: Six health science databases were searched from inception up to 21st January 2020. Quantitative studies investigating restraint use in residential aged care facilities that reported data from year 2000 onwards were included. Meta-analyses of binomial data using a random effect model were performed to pool proportions of physical or chemical restraints with 95% confidence intervals. Univariable meta-regression analyses were used to assess factors that may contribute to the variability in physical and chemical restraint prevalence. Multiple meta-regression analyses were performed where possible to construct models of factors contributing to these variations., Results: Eighty-five papers were included. The pooled proportion of physical and chemical restraint use in residential aged care facilities were 33% and 32% respectively. Bedrails (44%) and benzodiazepines (42%) were the most prevalent forms of physical and chemical restraint respectively. Studies from North America (lower prevalence) [coefficient (95% CI): -0.15 (-0.27, -0.03)], measurement approaches using direct observation (higher prevalence) [0.17 (0.02, 0.33)] and a combination of multiple measurement approaches (higher prevalence) [0.17 (0.05, 0.29)] explained 25.5% of variability in the prevalence of physical restraint. Multiple meta-regression analyses were not performed to identify factors that may explain the observed variability in chemical restraint prevalence due to the small number of studies with data available., Conclusion: Variability in prevalence of physical restraint could be explained partly by different measurement approaches and geographical regions. Valid and reliable measurement approaches across different regions is required to understand cultural differences due to geographical region effects on the prevalence of physical restraint use., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Use of high-risk medications is common and associated with adverse effects in older adults, including those living with dementia. A Computerised Clinical Decision Support System (CCDSS) called G-MEDSS© (Goal-directed Medication Review Electronic Decision Support System) contains tools that identify medications with anticholinergic and sedative effects and align older adult's health and medication goals of care with medication management strategies., Objectives: To describe the utility of a CCDSS called G-MEDSS in Home Medicines Review (HMR) by an accredited clinical pharmacist (ACP) using a mixed-methods process evaluation method., Methods: A mixed-methods process evaluation was conducted as part of a nation-wide cluster-randomised clinical trial evaluating the effectiveness of implementing G-MEDSS in HMR. Data were collected from ACPs and HMR recipients (the patient) using a feedback survey (ACPs and HMR recipients) and one-on-one telephone interviews (HMR recipients). Quantitative and qualitative data were combined at the start of analysis. Content analysis of the qualitative data was conducted, and emerging categories were linked to quantitative data., Results: Feedback surveys were completed by eight ACPs and 26 HMR recipients; 11 HMR recipients completed one-on-one telephone interviews. Overall, ACPs and HMR recipients who received the intervention reported a positive attitude towards the utility of G-MEDSS in HMR. ACPs reported that G-MEDSS enhanced their ability to make evidence-based recommendations about anticholinergic and sedative medications, and to better align HMR recommendations with HMR recipients' goals of care. However, ACPs described that it was difficult to obtain goals of care from HMR recipients. HMR recipients gave mixed reports about the ACPs consultations: some HMR recipients reported that they were engaged in discussions about their views on medications, whilst other participants reported that discussions about their concerns towards medications and goals was limited., Conclusions: This study suggests that a CCDSS, such as G-MEDSS, demonstrates good utility to assist ACPs to identify and assess anticholinergic and sedative medications. Given the mixed feedback from the ACPs on the different components of the G-MEDSS, further refinement of these tools and their use in combination in practice may be needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This systematic review aimed to identify thematic elements within definitions of physical and chemical restraint, compare explicit and implicit definitions, and synthesize reliability and validity of studies examining physical and/or chemical restraint use in long-term care. Studies were included that measured prevalence of physical and/or chemical restraint use, or evaluated an intervention to reduce restraint use in long-term care. 86 papers were included in this review, all discussed physical restraint use and 20 also discussed chemical restraint use. Seven themes were generated from definitions including: restraint method, setting resident is restrained in, stated intent, resident capacity to remove/control, caveats and exclusions, duration, frequency or number, and consent and resistance. None of the studies reported validity of measurement approaches. Inter-rater reliability was reported in 27 studies examining physical restraint use, and only one study of chemical restraint. Results were compared to an existing consensus definition of physical restraint, which was found to encompass many of the thematic domains found within explicit definitions. However, studies rarely applied measurement approaches that reflected all of the identified themes of definitions. It is necessary for a consensus definition of chemical restraint to be established and for measurement approaches to reflect the elements of definitions.

In the SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER) cluster-randomized controlled trial, we investigated the impact of a structured medication regimen simplification intervention on medication incidents in residential aged care facilities (RACFs) over a 12-month follow-up. A clinical pharmacist applied the validated 5-step Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE) for 96 of the 99 participating residents in the four intervention RACFs. The 143 participating residents in the comparison RACFs received usual care. Over 12 months, medication incident rates were 95 and 66 per 100 resident-years in the intervention and comparison groups, respectively (adjusted incident rate ratio (IRR) 1.13; 95% confidence interval (CI) 0.53-2.38). The 12-month pre/post incident rate almost halved among participants in the intervention group (adjusted IRR 0.56; 95%CI 0.38-0.80). A significant reduction in 12-month pre/post incident rate was also observed in the comparison group (adjusted IRR 0.67, 95%CI 0.50-0.90). Medication incidents over 12 months were often minor in severity. Declines in 12-month pre/post incident rates were observed in both study arms; however, rates were not significantly different among residents who received and did not receive a one-off structured medication regimen simplification intervention.

Aims: The Goal-directed Medication Review Electronic Decision Support System (G-MEDSS) assesses and reports a patient's goals, attitudes to deprescribing and Drug Burden Index (DBI) score, a measure of cumulative exposure to anticholinergic and sedative medications. This study evaluated the effect of implementing G-MEDSS in home medicines reviews (HMRs) on DBI exposure and clinical outcomes., Methods: A cluster-randomised clinical trial was performed across Australia. Accredited clinical pharmacists were randomised into intervention (G-MEDSS with usual care HMR) or comparison groups (usual care HMR alone). Patients were recruited by pharmacists from those routinely referred by general practitioners for HMR. The primary outcome was the proportion of patients with any reduction in DBI at 3-months follow-up. Secondary outcomes included change in DBI continuous score at 3-months, HMR recommendations to change DBI and clinical outcomes., Results: There were 201 patient participants at baseline (n = 88 intervention, n = 113 comparison), with 159 followed-up at 3-months (n = 63 intervention, n = 96 comparison). The proportion of patients with a reduction in DBI was not significantly different at 3-months (intervention 17%, comparison 11%; adjusted odds ratio 1.44, 95% confidence interval 0.56-3.80). Regarding secondary outcomes, there was no difference in change in DBI score at 3-months. However, the HMR report made recommendations to reduce DBI for a significantly greater proportion of patients in the intervention than in the comparison group (intervention 37%, comparison 14%; adjusted odds ratio 3.20, 95% confidence interval 1.50-6.90). No changes were observed in clinical outcomes., Conclusion: Implementation of G-MEDSS within HMR did not reduce patients' DBI at 3 months compared with usual care HMR., (© 2020 British Pharmacological Society.)

Background: The Frailty In Residential Sector over Time (FIRST) Study is a 3-year prospective cohort study investigating the health of residents living in residential aged care services (RACS) in South Australia. The study aims to examine the change in frailty status and associated health outcomes., Methods: This interim report presents data from March 2019-October 2020. The study setting is 12 RACS from one organisation across metropolitan and rural South Australia involving 1243 residents. All permanent (i.e. respite or transition care program excluded) residents living in the RACS for at least 8 weeks were invited to participate. Residents who were deemed to be medically unstable (e.g. experiencing delirium), have less than 3 months to live, or not fluent in English were excluded. Data collected included frailty status, medical diagnoses, medicines, pain, nutrition, sarcopenia, falls, dementia, anxiety and depression, sleep quality, quality of life, satisfaction with care, activities of daily living, and life space use at baseline and 12-months. Data Linkage will occur over the 3 years from baseline., Results: A total of 561 permanent residents (mean age 87.69 ± 7.25) were included. The majority of residents were female (n = 411, 73.3%) with 95.3% (n = 527) being classified as either frail (n = 377, 68.2%) or most-frail (n = 150, 27.1%) according to the Frailty Index (FI). Most residents were severely impaired in their basic activities of daily living (n = 554, 98.8%), and were at-risk of malnutrition (n = 305, 55.0%) and at-risk of sarcopenia (n = 492, 89.5%). Most residents did not experience pain (n = 475, 85.4%), had normal daytime sleepiness (n = 385, 69.7%), and low anxiety and depression scores (n = 327, 58.9%)., Conclusion: This study provides valuable information on the health and frailty levels of residents living in RACS in South Australia. The results will assist in developing interventions that can help to improve the health and wellbeing of residents in aged care services., Trial Registration: Prospectively registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12619000500156 ).

Rationale/aim: Medication administration is a complex and time-consuming task in residential aged care facilities (RACFs). Understanding the time associated with each administration step may help identify opportunities to optimize medication management in RACFs. This study aimed to investigate the time taken to administer medications to residents, including those with complex care needs such as cognitive impairment and swallowing difficulties., Method: A time-and-motion study was conducted in three South Australian RACFs. A representative sample of 57 scheduled medication administration rounds in 14 units were observed by a single investigator. The rounds were sampled to include different times of day, memory support units for residents living with dementia and standard units, and medication administration by registered and enrolled nurses. Medications were administered from pre-prepared medication strip packaging. The validated Work Observation Method By Activity Timing (WOMBAT) software was used to record observations., Results: Thirty nurses were observed. The average time spent on scheduled medication administration rounds was 5.2 h/unit of average 22 residents/day. The breakfast medication round had the longest duration (1.92 h/unit). Resident preparation, medication preparation and provision, documentation, transit, communication, and cleaning took an average of 5 minutes per resident per round. Medication preparation and provision comprised 60% of overall medication round time and took significantly longer in memory support than in standard units (66 vs 49 seconds per resident per round for preparation, 79 vs 58 for provision; P < .001 for both). Almost half (42%) of tablets/capsules were crushed in memory support units. The time taken for medication administration was not significantly different among registered and enrolled nurses., Conclusions: Nurses took an average of 5 minutes to administer medications per resident per medication round. Medication administration in memory support units took an additional minute per resident per round, with almost half of tablets and capsules needing to be crushed., (© 2020 John Wiley & Sons, Ltd.)

Objective: To investigate administration of pro re nata (PRN) medications and nurse-initiated medications (NIMs) in Australian aged care services over a 12-month period., Design: Twelve-month longitudinal audit of medication administrations., Setting and Participants: Three hundred ninety-two residents of 10 aged care services in regional Victoria, Australia., Methods: Records of PRN and NIM administration were extracted from electronic and hard copy medication charts. Descriptive statistics were used to calculate medication administration per person-month. Poisson regression was used to estimate predictors of PRN administration., Results: Over a median follow-up of 12 months (interquartile range 10-12 months), 93% of residents were administered a PRN medication and 41% of residents an NIM on 21,147 and 552 occasions, respectively. The mean number of any PRN administration was 5.85 per person-month. The most frequently administered PRN medications per person-month were opioids 1.54, laxatives 0.96, benzodiazepines 0.72, antipsychotics 0.48, paracetamol 0.46, and topical preparations 0.42. Three-quarters of residents prescribed a PRN opioid or PRN benzodiazepine and two-thirds of residents prescribed a PRN antipsychotic had the medication administered on 1 or more occasions over the follow-up., Conclusions and Implications: Most residents were administered PRN medications. Administration was in line with Australian regulations and institutional protocols. However, the high frequency of PRN analgesic, laxative, and psychotropic medication administration highlights the need for regular clinical review to ensure ongoing safe and appropriate use., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Falls are associated with considerable morbidity and mortality in aged care services and falls risk increasing drugs (FRIDs) are often overlooked as a contributor to falls. This study aims to investigate the association between the risk of falling and use of FRIDs from aged care services. Inverse-probability-weighted multinomial logistic regression was used to estimate the association between falls risk and regular FRIDs in 383 residents from six Australian aged care services. Overall, residents at high and low falls risk had similar prevalence of FRIDs. Prevalence of antipsychotics and sedative-hypnotics was low. Residents at high falls risk had higher adjusted odds of using ≥2 psychotropic medications (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.17-2.61) and ≥2 medications that cause/worsen orthostatic hypotension (OR = 3.59, 95% CI = 2.27-5.69). High prevalence of FRIDs was mainly attributable to medications for which residents had clinical indications. Clinicians appeared to have largely avoided FRIDs that explicit criteria deem potentially inappropriate for high falls risk.

Objectives: To investigate frailty prevalence, cross-sectional associations, predictive validity, concurrent validity, and cross-cultural adaptations of the FRAIL-NH scale., Design: Systematic review., Setting and Participants: Frail residents living in nursing homes., Methods: MEDLINE, EMBASE, CINAHL, and Cochrane Library were searched from January 2015 to June 2021 for primary studies that used the FRAIL-NH scale, irrespective of study designs and publication language., Results: Overall, 40 studies conducted across 20 countries utilized the FRAIL-NH scale; majority in Australia (n=14), followed by China (n=6), United States (n=3), and Spain (n=3). The scale has been translated and back-translated into Brazilian Portuguese, Chinese, and Japanese. Various cut-offs have been used, with ≥2 and ≥6 being the most common cut-offs for frail and most frail, respectively. When defined using these cut-offs, frailty prevalence varied from 15.1-79.5% (frail) to 28.5-75.0% (most frail). FRAIL-NH predicted falls (n=2), hospitalization or length of stay (n=4), functional or cognitive decline (n=4), and mortality (n=9) over a median follow-up of 12 months. FRAIL-NH has been compared to 16 other scales, and was correlated with Fried's phenotype (FP), Frailty Index (FI), and FI-Lab. Four studies reported fair-to-moderate agreements between FRAIL-NH and FI, FP, and the Comprehensive Geriatric Assessment. Ten studies assessed the sensitivity and specificity of different FRAIL-NH cut-offs, with ≥8 having the highest sensitivity (94.1%) and specificity (82.8%) for classifying residents as frail based on FI, while two studies reported an optimal cut-off of ≥2 based on FI and FP, respectively., Conclusion: In seven years, the FRAIL-NH scale has been applied in 20 countries and adapted into three languages. Despite being applied with a range of cut-offs, FRAIL-NH was associated with higher care needs and demonstrated good agreement with other well-established but more complex scales. FRAIL-NH was predictive of adverse outcomes across different settings, highlighting its value in guiding care for frail residents in nursing homes., Competing Interests: RV was previously a board member of Resthaven Inc. and is currently on the clinical governance committee. In the recent past, she has received honoraria, speakers and educational grants in various combinations from Nutricia, Abbott and Nestlé. JSB has received research grants paid to his employer from NHMRC, Dementia Australia Research Foundation, Yulgilbar Foundation, Dementia Centre for Research Collaboration, Victorian Government Department of Health and Human Services, GlaxoSmithKline Independent Medical Education, Aged Care Quality and Safety Commission, and several aged care provider organizations. SJL, SL and LAD declare no conflicts of interest.

Background: After a dementia diagnosis, goals of care are often reassessed, including the use of preventive medications like statins., Objective: To examine changes in statin use after initiating medication for managing dementia., Methods: A case-crossover study utilizing medication dispensing data from the Australian Pharmaceutical Benefits Scheme (PBS) 10% random sample was conducted. Use of statins was compared in the 12 months pre- and post-initiation (pre-period and post-period) of anti-dementia medications or risperidone for behavioural symptoms of dementia. Individuals aged ≥65 years who had their first dispensing of anti-dementia medication or risperidone between July 2006 and June 2017 and survived ≥12 months after their first supply were included. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for change in statin use in the discordant pairs., Results: The cohort (n = 19,809) had a median age of 81 years and 61% were female. Statins were less likely to be used after initiating anti-dementia medication or risperidone (OR 0.50; 95%CI 0.45-0.55). The OR for statin use in the post-period versus the pre-period decreased annually over the 11 years from 1.21; 95%CI 0.84-1.75 in 2006-7 to 0.31; 95%CI 0.24-0.41 in 2016-17 (p for interaction <0.05)., Conclusion: Statins are more likely to be ceased than started after initiating medication for dementia. This may reflect changes in goals of care, or changes in the interpretation of the available evidence for the safety and efficacy of statins in older people living with dementia., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: The risks of intensive blood glucose lowering may outweigh the benefits in vulnerable older people., Objectives: Our primary aim was to determine whether age, frailty, or dementia predict discharge treatment types for patients with type 2 diabetes (T2D) and related complications. Secondly, we aimed to determine the association between prior hypoglycemia and discharge treatment types., Design, Setting and Participants: We conducted a cohort study involving 3,067 patients aged 65-99 years with T2D and related complications, discharged from Melbourne's Eastern Health Hospital Network between 2012 and 2016., Measurements: Multinomial logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for the association between age, frailty, dementia and hypoglycemia, and being prescribed insulin-only, non-insulin glucose-lowering drugs (GLDs) or combined insulin and non-insulin GLDs compared to no GLD. International Classification of Diseases-10 codes were used to identify dementia status and prior hypoglycemia; frailty was quantified using the Hospital Frailty Risk Score., Results: Insulin-only, non-insulin GLDs, combined insulin and non-insulin GLDs, and no GLDs were prescribed to 19%, 39%, 20%, and 23% of patients, respectively. Patients >80 years were less likely than patients aged 65-80 to be prescribed any of the GLD therapies, (eg. non-insulin GLDs [OR 0.67; 95%CI 0.55-0.82]), compared to no GLD. Similarly, high vs. low frailty scores were associated with not being prescribed any of the three GLD therapies, (eg. non-insulin GLDs [OR 0.63; 95%CI 0.45-0.87]). However, dementia was not associated with discharge prescribing of GLD therapies. Patients with a hypoglycemia-related admission were more likely than those not hospitalized with hypoglycemia to receive insulin-only (OR 4.28; 95%CI 2.89-6.31)., Conclusions: Clinicians consider age and frailty when tailoring diabetes treatment regimens for patients discharged from hospital with T2D and related complications. There is scope to optimize prescribing for patients with dementia and for those admitted with hypoglycemia., Competing Interests: J.S.B. has received grant income paid to his employer from NHMRC, Australian Government Department of Health, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, GSK Independent Medical Education and several aged care provider organizations. M.C reports personal fees from Nestlé, outside the submitted work. J.I. reports grants from AstraZeneca, Amgen, Dementia Australia Research Foundation, National Health and Medical Research Council, and National Breast Cancer Foundation, outside the submitted work. S.W., D.J.M., L.F., and C.K. have no competing interests to declare.

Background: Older people use increasingly complex medication regimens. Complex regimens are challenging to administer, particularly for those with cognitive impairment, frailty, poor eyesight or limited dexterity. Complex regimens have been linked to non-adherence, medication errors and hospital admissions., Objective: The aim of this article is to describe strategies to reduce the complexity of medication regimens in community and residential aged care settings., Discussion: Medication regimen simplification is the process of reducing medication burden through strategies such as consolidating dosing times, standardising routes of administration, using long-acting rather than shorter-acting formulations, and switching to combination products in place of single-ingredient products. Obtaining a best possible medication history, ensuring appropriateness of current therapy, and deprescribing are important steps prior to implementing regimen simplification. Implementing such strategies should be based on a discussion and consideration of patient preferences, and include clinical judgement to limit the risk of unintended consequences for patients or carers.

Frailty is a geriatric condition associated with increased vulnerability to adverse drug events and medication-related harm. Existing clinical practice guidelines rarely provide medication management recommendations specific to frail older people. This report presents international consensus principles, generated by the Optimizing Geriatric Pharmacotherapy through Pharmacoepidemiology Network, related to medication management in frail older people. This consensus comprises 7 principles for clinical practice, 6 principles for research, and 4 principles for education. Principles for clinical practice include (1) perform medication reconciliation and maintain an up-to-date medication list; (2) assess and plan based on individual's capacity to self-manage medications; (3) ensure appropriate prescribing and deprescribing; (4) simplify medication regimens when appropriate to reduce unnecessary burden; (5) be alert to the contribution of medications to geriatric syndromes; (6) regularly review medication regimens to align with changing goals of care; and (7) facilitate multidisciplinary communication among patients, caregivers, and healthcare teams. Principles for research include (1) include frail older people in randomized controlled trials; (2) consider frailty status as an effect modifier; (3) ensure collection and reporting of outcome measures important in frailty; (4) assess impact of frailty on pharmacokinetics and pharmacodynamics; (5) encourage frailty research in under-researched settings; and (6) utilize routinely collected linked health data. Principles for education include (1) provide undergraduate and postgraduate education on frailty; (2) minimize low-value care related to medication management; (3) improve health and medication literacy; and (4) incorporate evidence in relation to frailty into clinical practice guidelines. These principles for clinical practice, research and education highlight different considerations for optimizing medication management in frail older people. These principles can be used in conjunction with existing best practice guidelines to help achieve optimal health outcomes for this vulnerable population. Implementation of the principles will require multidisciplinary collaboration between healthcare professionals, researchers, educators, organizational leaders, and policymakers., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Residential medication management reviews (RMMRs) are comprehensive medication reviews conducted by clinical pharmacists and general medical practitioners. RMMRs are the primary government-funded service to optimize medication management in Australian residential aged care facilities (RACFs) and are recommended for all new residents. This study investigated resident characteristics associated with timely RMMR provision within 90 days of RACF entry and national intrafacility variation in timely RMMR provision., Design: National retrospective cohort study., Setting and Participants: Individuals aged ≥65 years who first entered permanent residential aged care in Australia between January 1, 2012, and December 31, 2015, received at least 1 medication in the previous year, and were alive at 90 days post-RACF entry., Methods: Resident characteristics associated with timely RMMR provision were determined using multivariate logistic regression. Crude and risk-adjusted funnel plots were used to examine intrafacility variation in timely RMMR provision., Results: Of the 143,676 residents from 2799 RACFs included, 30,883 (21.5%) received an RMMR within 90 days. Resident characteristics associated with timely provision included dementia (adjusted odds ratio [aOR] 1.05, 95% confidence interval [CI] 1.02-1.08), primary language other than English (aOR 1.04, 95% CI 1.01-1.09), number of unique prescriptions dispensed in the previous year (aOR [per additional 5 prescriptions] 1.02, 95% CI 1.01-1.03), need for medication administration assistance (aORs ranged from 1.35 to 1.42, compared with residents self-managing) and facility remoteness (aORs ranged from 0.67 to 0.75 for residents outside major cities). The proportion of new residents receiving a timely RMMR ranged from 0% (n = 303 RACFs) to 100% (n = 4 RACFs). There were 174 RACFs (6.2%) in which ≥50% of new residents received a timely RMMR., Conclusions and Implications: Although there was some evidence that RMMRs are targeted to individuals with a greater burden of medication use and those living with dementia, considerable variation in provision exists nationally. This flagship medication review service is generally underutilized among residents of Australian RACFs., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Previous meta-analysis investigating the incidence and prevalence of hypoglycaemia in both types of diabetes is limited. The purpose of this review is to conduct a systematic review and meta-analysis of the existing literature which investigates the incidence and prevalence of hypoglycaemia in individuals with diabetes., Methods: PubMed, Embase and Cochrane library databases were searched up to October 2018. Observational studies including individuals with diabetes of all ages and reporting incidence and/or prevalence of hypoglycaemia were included. Two reviewers independently screened articles, extracted data and assessed the quality of included studies. Meta-analysis was performed using a random effects model with 95% confidence interval (CI) to estimate the pooled incidence and prevalence of hypoglycaemia in individuals with diabetes., Results: Our search strategy generated 35,007 articles, of which 72 studies matched the inclusion criteria and were included in the meta-analysis. The prevalence of hypoglycaemia ranged from 0.074% to 73.0%, comprising a total of 2,462,810 individuals with diabetes. The incidence rate of hypoglycaemia ranged from 0.072 to 42,890 episodes per 1,000 person-years: stratified by type of diabetes, it ranged from 14.5 to 42,890 episodes per 1,000 person-years and from 0.072 to 16,360 episodes per 1,000-person years in type 1 and type 2 diabetes, respectively., Conclusion: Hypoglycaemia is very common among individuals with diabetes. Further studies are needed to investigate hypoglycaemia-associated risk factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Comparative gastrointestinal bleeding (GIB) risk between rivaroxaban and low-dose aspirin is unknown in patients with atrial fibrillation (AF). This study investigated GIB risk with rivaroxaban vs aspirin among two separate AF cohorts in Hong Kong and the United Kingdom, using a common protocol approach., Methods: This was a population-based cohort study using separate data from the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority (2010-2018) and The Health Improvement Network (THIN) database in the United Kingdom (2011-2017). Patients with AF newly prescribed aspirin or rivaroxaban were included. Cox proportional hazards regression was used to compare GIB risks for rivaroxaban vs aspirin, accounting for confounders using propensity score fine stratification approach., Results: In CDARS, 29 213 patients were included; n = 1052 (rivaroxaban), n = 28 161 (aspirin). Crude GIB event rates per 100 patient-years in CDARS were 3.0 (aspirin) and 2.6 (rivaroxaban). No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.04, 95%CI = 0.76-1.42), and in dose-stratified analyses (HR = 1.21, 95%CI = 0.84-1.74 [20 mg/day]; HR = 0.80, 95%CI = 0.44-1.45 [≤15 mg/day]). In THIN, 11 549 patients were included, n = 3496 (rivaroxaban) and n = 8053 (aspirin). Crude GIB event rates were 1.3 (aspirin) and 2.4 (rivaroxaban) per 100 patient-years. No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.40, 95%CI = 1.00-1.98) and low-dose rivaroxaban (≤15 mg/day) (HR = 1.00, 95%CI = 0.56-1.30), but increased GIB risk was observed for rivaroxaban 20 mg/day vs aspirin (HR = 1.57, 95%CI = 1.08-2.29)., Conclusion: In patients with AF, GIB risk was comparable between aspirin and rivaroxaban ≤15 mg/day. GIB risk for rivaroxaban 20 mg/day vs aspirin remains uncertain and warrants further investigation., (© 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Medication review can be delivered using telehealth during the COVID-19 pandemic to ensure ongoing provision of care to vulnerable patient populations and to minimise risk of infection for both patients and health professionals., Objective: The aim of this article is to discuss the evidence related to telehealth medication reviews and provide practical considerations for conducting successful medication reviews by telehealth., Discussion: Leading up to the COVID-19 pandemic, telehealth technologies had been increasingly used to deliver medication review services, mainly to patients in rural and remote areas, and were accepted by patients. Available evidence suggests telehealth medication reviews may positively affect clinical and cost outcomes, but there are ongoing challenges. When delivering these services, appropriate preparation - using support people, maintaining patients' privacy, selecting the most suitable technology on the basis of individual circumstances and ensuring good communication between healthcare professionals involved in medication review cycle of care - can help produce best results for patients.

Background Underrepresentation of older people in clinical trials remains. This study aimed to examine the inclusion of older people and associated safety and efficacy reports from clinical trials of new molecular entities for cardiovascular disease indications since commencement of the US Food and Drug Administration Drug Trial Snapshot (DTS) Program. The DTS provides concise information on participants included in clinical trials supporting US Food and Drug Administration approval of new drugs. Methods and Results A cross-sectional analysis between January 1, 2015 and April 30, 2019 of DTS data including approval date, indication, number of trials and participants, age distribution, efficacy, and safety statements was conducted. Participation-to-prevalence ratio (PPR) was used to describe representation of older participants in trials relative to disease population. Efficacy and safety statements regarding age were compared with drug prescribing information. A total of 72 079 participants from 10 DTS reports were identified and 39 625 (55.0%) were aged ≥65 years old. Overall, 63.6% of cardiovascular disease DTS reports were representative of people aged ≥65 years old for specific cardiovascular disease conditions. Underrepresentation was observed in 4 DTS: 2 for heart failure (PPR 0.48 and 0.62), 1 for pulmonary arterial hypertension (PPR 0.72), and 1 for venous thromboembolism (PPR 0.38). Participants in clinical trials for new drugs for the treatment of atrial fibrillation (PPR 0.99 and 1.21) and hypercholesterolemia (PPR 0.84 and 0.97) were reflective of the older population for these diseases. An increased risk of adverse events in older participants was reported in 40% DTS safety statements but no differences were reported in the drug product information. Conclusions Despite the fact that >60% of cardiovascular disease trial participants for new molecular entities included in the DTS program were representative of the older population in real-world clinical practice, concerns remain for conditions including heart failure or venous thromboembolism. Drug product information safety statements regarding age differences in adverse events were not reflective of trial findings. An increased directive is needed to facilitate the generation of real-world evidence and appropriate reporting within drug product information for these potentially at-risk patient populations.

Background: Fall-related hospitalisations from residential aged care services (RACS) are distressing for residents and costly to the healthcare system. Strategies to limit hospitalisations include preventing injurious falls and avoiding hospital transfers when falls occur., Aims: To undertake a root cause analysis (RCA) of fall-related hospitalisations from RACS and identify opportunities for fall prevention and hospital avoidance., Methods: An aggregated RCA of 47 consecutive fall-related hospitalisations for 40 residents over a 12-month period at six South Australian RACS was undertaken. Comprehensive data were extracted from RACS records including nursing progress notes, medical records, medication charts, hospital summaries and incident reports by a nurse clinical auditor and clinical pharmacist. Root cause identification was performed by the research team. A multidisciplinary expert panel recommended strategies for falls prevention and hospital avoidance., Results: Overall, 55.3% of fall-related hospitalisations were among residents with a history of falls. Among all fall-related hospitalisations, at least one high falls risk medication was administered regularly prior to hospitalisation. Potential root causes of falling included medication initiations and dose changes. Root causes for hospital transfers included need for timely access to subsidised medical services or radiology. Strategies identified for avoiding hospitalisations included pharmacy-generated alerts when medications associated with an increased risk of falls are initiated or changed, multidisciplinary audit and feedback of falls risk medication use and access to subsidised mobile imaging services., Conclusions: This aggregate RCA identified a range of strategies to address resident and system-level factors to minimise fall-related hospitalisations.

Background: There is increasing international interest in initiatives to reduce medication-related harm and preventable hospitalizations in residential aged care services (RACS). The Australian Government recommends that RACS establish multidisciplinary Medication Advisory Committees (MACs). No previous research has specifically investigated the structures and functioning of MACs., Objectives: To explore the current structures and functioning of MACs, and identify opportunities for MACs to better promote safe and effective medication use., Methods: Semi-structured interviews and focus groups were conducted with a maximum variation sample of health professionals (n = 44) across four health services operating across 27 RACS in rural and regional Victoria, Australia. Qualitative data were analyzed using deductive and inductive content analyses. Results were presented to a multidisciplinary expert panel (n = 13) to identify opportunities for improvement., Results: Deductively coded themes included composition and functioning of the MAC, education and information needs and support to better manage polypharmacy. Emergent inductively coded themes included general medical practitioner (GP) and pharmacist engagement, collaboration and effectiveness. Participation by GPs and pharmacists was variable, while no MACs involved residents or family carers. Aged care specific and multidisciplinary MACs were generally more proactive in addressing potential medication-related harm. Education to identify and report adverse drug events with high risk medications was identified as a priority. The multidisciplinary panel made 12 recommendations to promote safe and effective medication use., Conclusion: Despite all MACs having a strong commitment to medication safety, opportunities exist to improve the composition and structure, proactive identification and response to emerging issues, and systems for staff, resident and family carer training., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Neurological and psychiatric (mental health) disorders have a large impact on health burden globally. Cognitive disorders (including dementia) and stroke are leading causes of disability. Mental health disorders, including depression, contribute up to one-third of total years lived with disability. The Neurological and mental health Global Epidemiology Network (NeuroGEN) is an international multi-database network that harnesses administrative and electronic medical records from Australia, Asia, Europe and North America. Using these databases NeuroGEN will investigate medication use and health outcomes in neurological and mental health disorders. A key objective of NeuroGEN is to facilitate high-quality observational studies to address evidence-practice gaps where randomized controlled trials do not provide sufficient information on medication benefits and risks that is specific to vulnerable population groups. International multi-database research facilitates comparisons across geographical areas and jurisdictions, increases statistical power to investigate small subpopulations or rare outcomes, permits early post-approval assessment of safety and effectiveness, and increases generalisability of results. Through bringing together international researchers in pharmacoepidemiology, NeuroGEN has the potential to be paradigm-changing for observational research to inform evidence-based prescribing. The first focus of NeuroGEN will be to address evidence-gaps in the treatment of chronic comorbidities in people with dementia.

Aim: To determine the patterns and predictors of pharmacological treatment initiation for type 2 diabetes and whether treatment initiation is consistent with Australian clinical practice guidelines that recommend metformin monotherapy., Methods: Individuals aged 40-99 years initiating a non-insulin type 2 diabetes medication between July 2013 and February 2018 were identified from a 10% random national sample of pharmacy dispensing data. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the predictors of initiating sulfonylurea monotherapy, non-guideline monotherapy and combination therapy compared with metformin monotherapy. Predictors included age, sex, initiation year and comorbidities determined using the Rx-Risk comorbidity index., Results: Of the 47 860 initiators, [47% women, mean age 60.7 (sd 12.1) years], 85.8%, 4.6%, 1.9% and 7.7% received metformin monotherapy, sulfonylurea monotherapy, non-guideline monotherapy and combination therapy, respectively. Increasing age was associated with increasing odds of initiating sulfonylurea monotherapy and non-guideline monotherapy. Combination therapy initiation was less likely in women (OR 0.74, 95% CI 0.69-0.79) and people with more comorbidities (e.g. OR 0.36, 95% CI 0.29-0.44 for seven or more comorbidities vs. no comorbidities) but more likely in congestive heart failure (OR 1.42, 95% CI 1.22-1.65), cerebrovascular disease (OR 1.50, 95% CI 1.32-1.69) and dyslipidaemia (OR 1.29, 95% CI 1.19-1.40)., Conclusion: Treatment initiation in Australia is largely consistent with clinical practice guidelines, with 86% of individuals initiating metformin monotherapy. Initiation on combination therapy was more common in men and in those with fewer comorbidities., (© 2019 Diabetes UK.)

Background: During the COVID-19 pandemic, vulnerable and older people with chronic and complex conditions have self-isolated in their homes, potentially limiting opportunities for consultations to have medications prescribed and dispensed., Objective: The aim of this article is to describe initiatives to ensure ongoing access to medications during the COVID-19 pandemic., Discussion: Cooperation between wholesalers and purchase limits in pharmacies have helped to ensure supply of essential medications. Therapeutic substitution by pharmacists is permitted for specific products authorised by the Therapeutic Goods Administration. Prescribers are permitted to issue digital image prescriptions, and implementation of electronic prescribing has been fast-tracked. Expanded continued dispensing arrangements introduced during the bushfire crises have been temporarily extended. Pharmacists are permitted to provide medication management reviews via telehealth. A Home Medicines Service has been introduced to facilitate delivery of medications to people who are vulnerable or elderly. Anticipatory prescribing and medication imprest systems are valuable for access to end-of-life medications within residential aged care.

Aims: The objective of this study is to investigate the association between multiple antihypertensive use and mortality in residents with diagnosed hypertension, and whether dementia and frailty modify this association., Methods: This is a two-year prospective cohort study of 239 residents with diagnosed hypertension receiving antihypertensive therapy across six residential aged care services in South Australia. Data were obtained from electronic medical records, medication charts and validated assessments. The primary outcome was all-cause mortality and the secondary outcome was cardiovascular-related hospitalizations. Inverse probability weighted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. Covariates included age, sex, dementia severity, frailty status, Charlson's comorbidity index and cardiovascular comorbidities., Results: The study sample (mean age of 88.1 ± 6.3 years; 79% female) included 70 (29.3%) residents using one antihypertensive and 169 (70.7%) residents using multiple antihypertensives. The crude incidence rates for death were higher in residents using multiple antihypertensives compared with residents using monotherapy (251 and 173/1000 person-years, respectively). After weighting, residents who used multiple antihypertensives had a greater risk of mortality compared with monotherapy (HR 1.40, 95%CI 1.03-1.92). After stratifying by dementia diagnosis and frailty status, the risk only remained significant in residents with diagnosed dementia (HR 1.91, 95%CI 1.20-3.04) and who were most frail (HR 2.52, 95%CI 1.13-5.64). Rate of cardiovascular-related hospitalizations did not differ among residents using multiple compared to monotherapy (rate ratio 0.73, 95%CI 0.32-1.67)., Conclusions: Multiple antihypertensive use is associated with an increased risk of mortality in residents with diagnosed hypertension, particularly in residents with dementia and among those who are most frail.

Objective: To assess the application of a structured process to consolidate the number of medication administration times for residents of aged care facilities., Design: A nonblinded, matched-pair, cluster randomized controlled trial., Setting and Participants: Permanent residents who were English-speaking and taking at least 1 regular medication, recruited from 8 South Australian residential aged care facilities (RACFs)., Methods: The intervention involved a clinical pharmacist applying a validated 5-step tool to identify opportunities to reduce medication complexity (eg, by administering medications at the same time or through use of longer-acting or combination formulations). Residents in the comparison group received routine care. The primary outcome at 4-month follow-up was the number of administration times per day for medications charted regularly. Resident satisfaction and quality of life were secondary outcomes. Harms included falls, medication incidents, hospitalizations, and mortality. The association between the intervention and primary outcome was estimated using linear mixed models., Results: Overall, 99 residents participated in the intervention arm and 143 in the comparison arm. At baseline, the mean resident age was 86 years, 74% were female, and medications were taken an average of 4 times daily. Medication simplification was possible for 62 (65%) residents in the intervention arm, with 57 (62%) of 92 simplification recommendations implemented at follow-up. The mean number of administration times at follow-up was reduced in the intervention arm in comparison to usual care (-0.36, 95% confidence interval -0.63 to -0.09, P = .01). No significant changes in secondary outcomes or harms were observed., Conclusions and Implications: One-off application of a structured tool to reduce regimen complexity is a low-risk intervention to reduce the burden of medication administration in RACFs and may enable staff to shift time to other resident care activities., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine risks of embolic events, bleeding, and mortality with direct oral anticoagulants (DOACs) vs warfarin in people with atrial fibrillation (AF) and dementia., Design: New-user retrospective cohort study using The Health Improvement Network database., Setting and Participants: A population-based sample comprising people with AF and dementia prescribed DOACs or warfarin from August 2011 to September 2017., Methods: Risk of ischemic stroke (IS), ischemic stroke/transient ischemic attack/systemic embolism (IS/TIA/SE), all-cause mortality, intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and other bleeding were compared for DOACs vs warfarin using propensity score-adjusted Poisson regression. Incidence rate ratios (IRRs) and absolute risk differences (ARDs) were calculated., Results: Overall, 2399 people with AF and dementia initiated DOACs (42%) or warfarin (58%). Before propensity score adjustment, patients who initiated DOACs were older and had more comorbidities. After adjustment, DOAC initiators demonstrated similar risks of IS, TIA, or SE; IS alone; and other bleeding but reduced ICB risk (IRR 0.27, 95% CI 0.08, 0.86; ARD -5.2, 95% CI -6.5, -1.0, per 1000 person-years) compared with warfarin. Increased risk of GIB (IRR 2.11, 95% CI 1.30, 3.42; ARD 14.8, 95% CI 4.0, 32.4, per 1000 person-years) and all-cause mortality (IRR 2.06, 95% CI 1.60, 2.65; ARD 53.0, 95% CI 30.2, 82.8, per 1000 person-years) were observed in DOAC initiators compared with warfarin., Conclusions and Implications: Among people with AF and dementia, initiating treatment with DOACs compared with warfarin was associated with similar risks of IS, TIA, or SE and IS alone. DOAC-treated patients demonstrated reduced ICB risk but increased GIB and all-cause mortality risks. We cannot exclude the possible impact of residual confounding from channeling of DOACs toward older and sicker people, particularly for the outcome of all-cause mortality. Further safety data are urgently needed to confirm findings., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Ocular issues are common, burdensome, and under-researched among residents of aged care services. This study aims to investigate the prevalence of dry eyes or use of ocular lubricants among residents, and the possible association with systemic medications known or suspected to cause dry eyes. A cross-sectional study of 383 residents of six aged care services in South Australia was conducted. Data were extracted from participants' medical histories, medication charts, and validated assessments. The main exposure was systemic medications known to cause, contribute to, or aggravate dry eyes. The primary outcome was documented dry eyes or regular administration of ocular lubricants. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between systemic medications and dry eyes/use of ocular lubricants. Dry eyes were documented for 53 (13.8%) residents and 98 (25.6%) residents were administered ocular lubricants. Overall, 116 (30.3%) residents had documented dry eyes/used ocular lubricants. Of these, half ( n = 58) were taking a medication known to cause, contribute to, or aggravate dry eyes. Taking one or more medications listed as known to cause dry eyes was associated with having dry eyes/use of ocular lubricants (OR 1.83, 95% CI 1.15-2.94). In sub-analyses, no individual medication was associated with dry eyes/use of ocular lubricants. Dry eyes and use of ocular lubricants are common in residential aged care. Our hypothesis generating findings suggest the need for further research into the clinical significance of systemic medications as a possible cause of dry eyes.

Background: The longitudinal pattern of medication use among family caregivers of people with dementia is not well understood, despite the potential for medication over- or under-use., Objectives: To investigate caregiver medication use over a five-year follow-up using data obtained via self-report and from a national prescription register, and compare agreement between medication data obtained from the two sources., Methods: Medication data for 222 family caregivers of people with Alzheimer's disease were obtained via self-report and from the Finnish Social Insurance Institution. Generalised estimating equations, Kappa statistics and related samples Wilcoxon signed rank test were used to analyse medication use over time., Results: The mean number of medications used by caregivers increased from 3.4 to 4.1 (self-reported current regular medications) and 2.4 to 2.8 (reimbursed prescription medications during the past 90 days) over five years (p < 0.001). Significantly, more medications were identified via self-report (mean 3.6, SD = 3.3) than the national prescription register (mean 2.6, SD = 2.4, Z= -12.300, p < 0.001). Agreement between the two data sources was good for cardiovascular medications and anti-hypertensives (Kappa = 0.883-0.967, p < 0.001) and medications for acid-related disorders (Kappa = 0.508-0.092, p < 0.001). Agreement was moderate for analgesics (Kappa = 0.281-0.477, p < 0.001) and psychotropics (Kappa = 0.281-0.562, p < 0.002). The proportion of caregivers using five or more medications increased from 27.5% to 44.6% (self-report), and 16.7% to 27.7% (register) (p < 0.001)., Conclusion: Caregivers use an increasing number of medications in the first five years of caring for persons with dementia, and self-report using a higher number of medications than data from the national prescription register suggest.

Background: Statins are associated with muscle-related adverse events, but few studies have investigated the association with fall-related hospitalizations among residents of long-term care facilities (LTCFs)., Objective: The objective of the study is to investigate whether statin use is associated with fall-related hospitalizations from LTCFs., Methods: A case-control study was conducted among residents aged ≥65 years admitted to hospital from 2013 to 2015. Cases (n = 332) were residents admitted for falls and fall-related injuries. Controls (n = 332) were selected from patients admitted for reasons other than cardiovascular and diabetes. Cases and controls were matched 1:1 by age (±2 years), index date of admission (±6 months), and sex. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression, after considering for history of falls, hypertension, dementia, functional comorbidity index, polypharmacy (≥9 regular preadmission medications), and fall-risk medications. Subanalyses were performed for individual statins, dementia, and statin intensity., Results: Overall, 43.1% of cases and 27.1% of controls used statins. Statins were associated with fall-related hospitalizations (aOR = 2.24, 95% CI 1.56-3.23), in particular simvastatin (aOR = 2.26, 95% CI 1.22-4.20) and atorvastatin (aOR = 2.08, 95% CI 1.33-3.24). Statins were associated with fall-related hospitalizations in residents with (aOR = 2.34, 95% CI 1.33-4.11) and without dementia (aOR = 2.30, 95% CI 1.46-3.63). There was no association between statin intensity and fall-related hospitalizations (aOR = 0.78, 95% CI 0.43-1.40)., Conclusion: This study suggests a possible association between statin use and fall-related hospitalizations among residents living in LTCFs. However, there was minimal evidence for a relationship between statin intensity and fall-related hospitalizations. Further research is required to substantiate these hypothesis-generating findings., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

A cross-linking technique involving application of Bacteriochlorophyll Derivative WST-11 mixed with dextran (WST-D) to the epithelium-debrided cornea and illumination with Near Infrared (NIR), has been identified as a promising therapy for stiffening pathologically weakened corneas. To investigate its effect on corneal collagen architecture, x-ray scattering and electron microscopy data were collected from paired WST-D/NIR treated and untreated rabbit corneas. The treated eye received 2.5 mg/mL WST-D and was illuminated by a NIR diode laser (755 nm, 10 mW/cm 2 ). An increase in corneal thickness (caused by corneal oedema) occurred at 1-day post-treatment but resolved in the majority of cases within 4 days. The epithelium was fully healed after 6-8 days. X-ray scattering revealed no difference in average collagen interfibrillar spacing, fibril diameter, D-periodicity or intermolecular spacing between treated and untreated specimens. Similarly, electron microscopy images of the anterior and posterior stroma in healed WST-D/NIR corneas and untreated controls revealed no obvious differences in collagen organisation or fibril diameter. As the size and organisation of stromal collagen is closely associated with the optical properties of the cornea, the absence of any large-scale changes following treatment confirms the potential of WST-D/NIR therapy as a means of safely stiffening the cornea.

Background: Global Initiative for Asthma step 5 therapies (GINA-5), other than inhaled corticosteroids and long-acting β-agonists in fixed dose combinations (ICS/LABA FDC), often entail more expensive (eg, monoclonal biologics) or less safe (eg, maintenance oral corticosteroids [OCS]) treatments. It is therefore important to assess poor inhaler adherence as a possible cause of suboptimal response to ICS/LABA FDC before additional GINA-5., Objective: To determine rates of, and time to, additional GINA-5 after first-year ICS/LABA FDC use, and their association with inhaler adherence., Methods: Patients initiating ICS/LABA FDC between 2013 and 2017 were identified from Australian national dispensing data. Group-based trajectory modeling was used to estimate medication adherence patterns. Multivariable Cox proportional hazards models were used to examine the association between adherence trajectories and GINA-5 addition during 2-year follow-up., Results: In total, 3062 new ICS/LABA FDC users were identified, of whom 120 (3.9%) received additional GINA-5 (OCS: 89; long-acting muscarinic antagonists: 39; biologics: <3). Mean time to commencing additional GINA-5 was 705.2 (standard deviation, 1.7) days. Adherence trajectories were nonpersistent use (20%), seasonal use (8%), poor adherence (58%), and good adherence (13%). Although poor adherence was associated with longer time to additional GINA-5 (adjusted hazard ratio: 0.58; 95% confidence interval: 0.35-0.95), over 80% of additional GINA-5 was commenced in poorly adherent patients. Use of ≥2 OCS/antibiotic courses also predicted additional GINA-5., Conclusions: Almost 1 in 20 people with asthma commenced additional GINA-5 after ICS/LABA initiation, most of whom (>80%) were poorly adherent to inhaled preventers. There is a substantial unmet need for inhaler adherence to be addressed before prescribing additional GINA-5., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Strong and high-dose opioids are associated with opioid overdose and death. The objective of this study was to determine the rate and predictors of transitioning to high-dose or strong opioids among people initiating opioids., Design: Retrospective cohort study., Setting: Australia., Participants: People initiating opioid analgesics from July 2013 to January 2018 were identified from a random 10% sample of Australia's Pharmaceutical Benefits Scheme eligible population., Measurements: Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the predictors of escalating to ≥ 50 mg oral morphine equivalents (OMEs)/day (cohort 1); ≥ 90 mg OMEs/day (cohort 2) and transitioning from weak opioids to strong opioids (cohort 3) over 12 months of follow-up. Predictors included age, sex, number of comorbidities, history of depression, prior treatment for cancer and selected other medication use., Findings: In total, 861 691 people initiated opioids at average doses < 50 mg OMEs/day (cohort 1), 874 401 at < 90 mg OMEs/day (cohort 2) and 603 884 initiated weak opioids (cohort 3). Overall, 1.4% of people escalated to doses ≥ 50 mg OMEs/day, 0.8% to doses ≥ 90 mg OMEs/day and 7.3% transitioned to strong opioids. The strongest predictors of transitioning included prior treatment for cancer [cohort 1: HR = 3.19, 95% CI = 3.00-3.40; cohort 2: HR = 4.19, 95% CI = 3.90-4.51; cohort 3: HR = 2.07, 95% CI = 1.95-2.18] and age ≥ 75 years (cohort 1: HR = 3.04, 95% CI = 2.73-3.38; cohort 2: HR = 2.51, 95% CI = 2.17-2.89; cohort 3: HR = 1.88, 95% CI = 1.80-1.96). Females transitioned to high doses and strong opioids less rapidly than males (cohort 1: HR = 0.79, 95% CI = 0.76-0.82; cohort 2: HR = 0.70, 95% CI = 0.66-0.73; cohort 3: HR = 0.95, 95% CI = 0.93-0.96)., Conclusions: In Australia, more than one in every 13 people initiating weak opioids transition to strong opioids. By extrapolation, more than 26 000 Australian adults initiating opioids escalate to high doses each year. People with cancer treatment history, older people and males transition to strong and high-dose opioids more rapidly than others., (© 2019 Society for the Study of Addiction.)

Background and Objectives: Frailty is a dynamic process with potential transitions over time. However, there is limited understanding of the patterns of frailty improvement. We conducted a systematic review and meta-analysis to estimate the natural rate of frailty regression among community-dwelling older adults aged at least 60 years., Research Design and Methods: Systematic searches for studies reporting frailty improvement were performed in 5 databases (Medline, Embase, CINAHL plus, Web of Science, and PsycINFO) from inception until January 2019., Results: Twenty-five studies from 26 countries were included. Among a baseline population of more than 50,000 individuals, the pooled prevalence of pre-frailty and frailty was 50.5% (95% confidence interval [CI] 47.8-53.3) and 12.8% (95% CI 9.1-17.0), respectively. During a median follow-up of 3.0 (range 1-10.0) years, 23.3% of surviving pre-frail individuals regressed to a robust state and 35.2% of surviving frail individuals reversed to a pre-frail or robust state. The pooled remission rates among people with pre-frailty and frailty were 80.4 (95% CI 61.7-104.6) and 135.3 (95% CI 98.1-186.5) per 1,000 person-years, respectively. Frailty and pre-frailty improvement rates varied by sex, diagnostic criteria, study region, and follow-up duration. The remission rates were significantly reduced when accounting for progressions to death. The heterogeneity of included studies was high which reflected considerable differences in methodological approach., Discussion and Implications: Although frailty is highly prevalent in older people, natural remission is possible and common. Improved understanding of the factors that confer increased likelihood of frailty regression may support the design of interventions to reduce the burden of frailty., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate oral anticoagulant (OAC) prescribing trends in type 2 diabetes mellitus (T2DM) in the UK from 2001 to 2015., Design: A cross-sectional drug utilisation study., Setting: Electronic health records from The Health Improvement Network primary care database in the UK., Participants: Individuals with T2DM who received a record of OAC prescription., Outcome Measures: The prescribing trends of OAC medications in individuals with T2DM were examined from 2001 to 2015, stratified by age, gender and therapeutic classifications., Results: A total of 361 635 individuals with T2DM were identified, of whom 36 570 were prescribed OAC from 2001 to 2015. The prevalence of OAC prescribing increased by 50.0%, from 1781 individuals receiving OAC prescriptions (IROACP) (4.4 (95% CI 4.2 to 4.6) per 100 persons) in 2001, to 17 070 IROACP (6.6 (95% CI 6.5 to 6.7) per 100 persons) in 2015. The prevalence of warfarin prescribing decreased by 14.0%, from 1761 individuals receiving warfarin prescriptions (IRWP) (98.9 (95% CI 98.4 to 99.4) per 100 persons) in 2001, to 14 533 IRWP (85.1 (95% CI 84.6 to 85.7) per 100 persons) in 2015. This corresponded with increased prescribing of direct oral anticoagulants (DOACs), from 18 individuals receiving DOAC prescriptions (IRDOACP) (0.1 (95% CI 0.08 to 0.23) per 100 persons) in 2010, to 3016 IRDOACP (17.6 (95% CI 17.1 to 18.2) per 100 persons) in 2015, during the same period., Conclusions: Prescribing of OACs in individuals with T2DM increased from 2001 to 2015. Since the introduction of DOACs, there has been a clear shift in prescribing towards these agents. Future studies are needed to assess the safety of coadministration of OAC medications and antidiabetic therapy with T2DM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Infections are leading causes of hospitalizations from residential aged care services (RACS), which provide supported accommodation for people with care needs that can no longer be met at home. Preventing infections and early and effective management are important to avoid unnecessary hospital transfers, particularly in the Australian setting where new quality standards require RACS to minimize infection-related risks. The objective of this study was to examine root causes of infection-related hospitalizations from RACS and identify strategies to limit infections and avoid unnecessary hospitalizations. An aggregate root cause analysis (RCA) was undertaken using a structured local framework. A clinical nurse auditor and clinical pharmacist undertook a comprehensive review of 49 consecutive infection-related hospitalizations from 6 RACS. Data were collected from nursing progress notes, medical records, medication charts, hospital summaries, and incident reports using a purpose-built collection tool. The research team then utilized a structured classification system to guide the identification of root causes of hospital transfers. A multidisciplinary clinical panel assessed the root causes and formulated strategies to limit infections and hospitalizations. Overall, 59.2% of hospitalizations were for respiratory, 28.6% for urinary, and 10.2% for skin infections. Potential root causes of infections included medications that may increase infection risk and resident vaccination status. Potential contributors to hospital transfers included possible suboptimal selection of empirical antimicrobial therapy, inability of RACS staff to establish on-site intravenous access for antimicrobial administration, and the need to access subsidized medical services not provided in the RACS (e.g., radiology and pathology). Strategies identified by the panel included medication review, targeted bundles of care, additional antimicrobial stewardship initiatives, earlier identification of infection, and models of care that facilitate timely access to medical services. The RCA and clinical panel findings provide a roadmap to assist targeting services to prevent infection and limit unnecessary hospital transfers from RACS.

Background: Warfarin is underutilised in frail older people because of the fear of bleeding complications. Drug interactions are an independent bleeding risk factor. However, the extent to which potential drug interactions are taken into account at warfarin therapy initiation in frail patients is not known., Objective: The objective of this study was to investigate the use of potentially interacting drugs increasing the bleeding risk before and after warfarin initiation in frail and non-frail patients., Methods: We conducted an observational study including inpatients aged ≥ 60 years initiated on warfarin in a tertiary hospital in Adelaide, South Australia. Frailty status was assessed with the Reported Edmonton Frail Scale. Medication charts were reviewed before and after warfarin initiation., Results: In total, 151 patients (102 non-frail and 49 frail) were included. Before warfarin initiation, the use of clopidogrel and acetaminophen was more common in frail patients compared with non-frail patients (25.5% vs 10.2%, p = 0.0135, 63.8% vs 35.7% p = 0.0014, respectively). The use of non-steroidal anti-inflammatory drugs, 9.2% in non-frail patients and 6.4% in frail patients before warfarin initiation, was completely stopped after warfarin initiation in both groups. The use of antiplatelet drugs decreased from 56.1% in non-frail patients and 66.0 % in frail patients to 12.2% and 14.9%, respectively. Instead, the use of drugs affecting the metabolism of warfarin or vitamin K increased in both groups. No statistically significant difference was seen in the exposure to interacting drugs between study groups after warfarin initiation. Acetaminophen, senna glycosides and cytochrome P450 2C9 inhibiting drugs were the most common interacting drugs at discharge used in 49.0%, 18.4% and 20.4% of non-frail patients and 53.2%, 29.8% and 19.1% of frail patients, respectively., Conclusions: The overall frequency of potential drug interactions was moderate and frail patients were not exposed to warfarin drug interactions more often than non-frail patients. Further studies in larger study populations are required to verify these results.