Background: The proportion of frail older people is growing in Australia and Malaysia with implications in all sectors of society. The prevalence of polypharmacy and use of potentially inappropriate medications (PIMs) is highest among the oldest old (≥80 years), especially women. Medication reviews can optimise medications although the outreach of medication reviews in Malaysia is limited. In Australia, Residential Medication Management Reviews (RMMRs) and Home Medicines Reviews (HMRs) are remunerated by the Government. There is little evidence about the association between frailty, polypharmacy and PIMs, andthe impact of RMMRs and HMRs and associated medication costs. Therefore, this thesis determined common combinations of medications to underpin prevalence and associations between polypharmacy, PIMs and frailty, and the uptake and impact of RMMRs and HMRs. In Malaysia, the algorithm that underpinned an app to facilitate medication reviews, MedReview, was designed by the candidate and evaluated. Methods: Data were obtained from participants enrolled in the Australian Longitudinal Study on Women’s Health from 2003 (aged 77 to 82 years) to 2017 (aged 91 to 96 years). Latent class analysis was used to determine medication combinations, and generalised estimating equations were used in regression analyses to determine associations over time. Data from a validated questionnaire distributed among Malaysian community pharmacists were rigorously evaluated using factor analysis. Results: Frail women aged ≥77 years had an 8% increased risk of having continuous polypharmacy and a 2% increased risk of using PIMs, both when adjusted for othercharacteristics. There was a high tendency to medications of multiple anatomical groups, including regular use of antiinfectives. In 2017, only 26% of eligible women residing in aged care and 3% of eligible women residing in the community received RMMRs and HMRs, respectively. RMMRs did not reduce the use of PIMs and polypharmacy, whereas HMRs increased polypharmacy and PIMs, in the following year. Women experienced increased out-of-pocket (OOP) medication and PIM costs over time, with women who 25 received medication reviews having higher OOP costs. In Malaysia, community pharmacistshad a positive attitude about the MedReview app and intended to use it, finding it trustworthy. Conclusions: The thesis provides evidence that medications for older people can still be optimised, especially for the frail oldest old, and that the RMMRs and HMRs in Australia may not be appropriately targeting this segment of the population. The evidence can be used by policy-makers in Australia and provides a reference point for other countries. This study also provided a platform to encourage the uptake of medication reviews in Malaysia, Australia and elsewhere, by designing and evaluating the MedReview app. Keywords: Frailty, Home Medicines Review, medication costs, medication reviews, medication use, older women, polypharmacy, potentially inappropriate medications, Residential Medication Management Reviews, technology

Medication reviews form the backbone of pharmacotherapy optimisation among the older population. Acknowledging the association of frailty and quality of life with medication appropriateness is beneficial in optimising medications among the elderly. This study developed an individualised approach to medication management among older people residing in aged care facilities, and assessed their frailty and quality of life. The approach is centred on medication appropriateness and comprises a five-step medication review algorithm that is supplemented with a 10-component tool, the Medication Appropriateness Index-Geriatric version (MAI-G). The MAI-G incorporates geriatric components and is useful in quantifying medication appropriateness. The components in the MAl-G closely correspond to components in the algorithm to allow for quick and unequivocal extrapolation. The algorithm and MAI-G were implemented in a 6-month prospective study among 202 residents aged 65 years and above across 17 aged care facilities in Klang Valley, Malaysia. The mean age ± standard deviation of the participants was 76.81 ± 7.79 years, with females dominating the study population (62.4%). The number of inappropriate medications detected by the MAI-G decreased from 0.83 ± 0.93 at baseline, to 0.76 ± 0.92 at 6- months. The proportion of inappropriate medications detected by the MAl-G that were not detected by the MAl was high, 39.7% at baseline, 34.8% at 3-months and 34.3% at 6-months. Interestingly frailty and quality of life status improved at 6-months although there was no statistically significant association between medication appropriateness and the risk of reporting frailty (OR 4.64, 95% CI: 0.83-25.76), or medication appropriateness and the risk of reporting poor quality of life, at 6-months (OR 1.60, 95% CI: 0.47-5.49). This study provides an overview of the frailty and quality of life status of aged care residents in Malaysia, and suggests that urgent attention from health care professionals is warranted, to improve their health care, particularly the prescribing of potentially inappropriate medications. The findings support the need for a comprehensive medication review process that is supplemented by a medication appropriateness quantification tool which is geriatric-specific.