A Digitally Enabled, Pharmacist service to detecT medicine harms in residential aged care (nursing home) (ADEPT): protocol for a feasibility study.

INTRODUCTION: This feasibility study aims to develop and test a new model of practice in Australia using digital technologies to enable pharmacists to monitor early signs and symptoms of medicine-induced harms in residential aged care. METHODS AND ANALYSIS: Thirty residents will be recruited from an aged care facility in South Australia. The study will be conducted in two phases. In phase I, the study team will work with aged care software providers and developers of digital technologies (a wearable activity tracker and a sleep tracking sensor) to gather physical activity and sleep data, as well as medication and clinical data from the electronic medication management system and aged care clinical software. Data will be centralised into a cloud-based monitoring platform (TeleClinical Care (TCC)). The TCC will be used to create dashboards that will include longitudinal visualisations of changes in residents' health, function and medicine use over time. In phase II, the on-site pharmacist will use the centralised TCC platform to monitor each resident's medicine, clinical, physical activity and sleep data to identify signs of medicine-induced harms over a 12-week period.A mixed methods process evaluation applying the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) evaluation framework will be used to assess the feasibility of the service. Outcome measures include service reach, changes in resident symptom scores (measured using the Edmonton Symptom Assessment System), number of medication adverse events detected, changes in physical activity and sleep, number of pharmacist recommendations provided, cost analysis and proportion of all pharmacists' recommendations implemented at 4-week, 8-week and 12-week postbaseline period. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of South Australia's Human Research Ethics Committee (205098). Findings will be disseminated through published manuscripts, conference presentations and reporting to the study funder. TRIAL REGISTRATION NUMBER: ACTRN12623000506695.

Data-Driven Interventions for an Emergency Preparedness System: A National Experience in Australia.

Natural disasters and health emergencies disproportionally affect vulnerable populations causing disruptions to usual care and increasing chronic disease burden. Data and digital technologies are important tools to identify and mitigate indirect effects of emergencies. In this paper, we describe the methods used in the development of a series of digital emergency preparedness interventions to mitigate the direct and indirect consequences of the COVID-19 pandemic in the veteran community in Australia. The case studies demonstrate the use of data for surveillance, patient phenotyping, data-driven decision support and stakeholder communication in primary care. The intervention successfully increased appropriate healthcare use by vulnerable individuals and could be expanded to other populations.

To test or to not test: A retrospective cross-sectional study on potentially inappropriate use of pathology testing in South Australian hospitals.

OBJECTIVES: To measure rates of potentially inappropriate pathology testing in the hospital setting. METHODS: Retrospective cross-sectional study in hospital setting from July 2021 to December 2021. We examined 3 potentially inappropriate uses: overordering, selection errors, and unnecessary repeat testing. Overordering included vitamin D and lipids (rarely required in acute hospital care). Selection error was the ratio of iron studies to standalone ferritin requests. Unnecessary repeats included any repeat vitamin D, lipids, iron, or ferritin in an episode of care or C-reactive protein (CRP) repeated within 3 days and N-terminal pro-brain natriuretic peptide (NT-proBNP) within 7 days and repeated previously abnormal CRP and NT-proBNP tests. Costs of inappropriate tests were estimated using the Australian Medicare Benefits Schedules. RESULTS: Among 55,904 test requests, 15% (n = 8120) were potentially inappropriate. Vitamin D was frequently ordered (n = 4498), as were lipids (n = 2872). Ratio of iron studies to standalone ferritin was 36. Of 19,233 repeat CRPs, 36% (n = 6947) were within 3 days and 62% (n = 179) of repeat NT-proBNPs were within 7 days of the first test. For initially abnormal tests, 89% of CRPs and 97% of NT-proBNPs remained abnormal. Inappropriate test costs accounted for 12% to 30% of costs. CONCLUSIONS: Frequent potential inappropriate use and selection of pathology tests was observed in South Australian hospitals.

Temporal trends in percutaneous coronary intervention in Australia: A retrospective analysis from 2000-2021.

OBJECTIVE: The aim of this study was to describe the trend in percutaneous coronary intervention (PCI) with insertion of a stent in Australia from 2000/01 to 2020/21 and investigate trends in same-day versus non-same-day discharge following PCI. A secondary aim was to compare the rate of coronary artery bypass grafting (CABG) with PCI procedures, while a third aim was to compare marked PCI trend changes with the PCI guidelines during the study period. BACKGROUND: PCI with stent deployment is the most common form of interventional treatment for coronary artery disease, and its use has been expanding since 2000. However, there is a lack of descriptive studies of the national trend in Australia. METHODS: All procedures for PCI and CABG were extracted across 21 years (2000/01 to 2020/21) from the Australian Institute of Health and Welfare data. Age-standardized rates were calculated using the Australian standard population as of June 2001. The ratio of PCI to CABG procedures was also calculated. Trends for PCI were stratified by age, gender, and same-day or overnight discharge episodes. Linear regression analysis was done to compare the age-standardized rates across different age categories. Segmented regression analysis was performed to ascertain the change in the age-standardized rates of PCI during the study period. Whether the changepoints in the trend were matched with guideline updates was also assessed. RESULTS: There were 751 728 PCI procedures in persons aged 30 years and above between 2000/01 and 2020/21. The age-standardized rate for the study period showed that persons aged 60-74 years had a higher rate of procedures (102.7) compared to persons aged 30-59 years (81.3) and 75 years and older (61.8) (P < 0.001). There were two statistically significant changepoints in the overall trend; 2005/06 and 2013/14, matched with the change in PCI guidelines. Despite the lower number of procedures for same-day discharge episodes, there has been an increasing trend since 2014/15. More than two-thirds of all stenting procedures were the insertion of a single stent. PCI to CABG procedure ratio increased from 0.6 in 2000/01 to 1.8 in 2020/21. CONCLUSIONS: There was a varying trend in the age-standardized rate of PCI with a peak in 2005/06. The trend appears to be stabilizing in the later part of the study period, but the rate for same-day discharge episodes showed an increasing trend after 2014/15. There is consistency with changepoints in the trend and updated PCI guideline recommendations. The ratio of PCI with insertion of a stent to CABG procedure increased substantially across the study period.

Opportunities for clinical decision support targeting medication safety in remote primary care management of chronic kidney disease: A qualitative study in Northern Australia.

INTRODUCTION: This study aimed to identify opportunities for clinical decision support targeting medication safety in remote primary care, by investigating the relationship between clinical workflows, health system priorities, cognitive tasks, and reasoning processes in the context of medicines used in people with chronic kidney disease (CKD). METHODS: This qualitative study involved one-on-one, semistructured interviews. The participants were healthcare professionals employed in a clinical or managerial capacity with clinical work experience in a remote health setting for at least 1 year. RESULTS: Twenty-five clinicians were interviewed. Of these, four were rural medical practitioners, nine were remote area nurses, eight were Aboriginal health practitioners, and four were pharmacists. Four major themes were identified from the interviews: (1) the need for a clinical decision support system to support a sustainable remote health workforce, as clinicians were "constantly stretched" and problems may "fall through the cracks"; (2) reliance on digital health technologies, as medical staff are often not physically available and clinicians-on-duty usually "flick an email and give a call so that I can actually talk it through to our GP"; (3) knowledge gaps, as "it takes a lot of mental space" to know each patient's renal function and their medication history, and clinicians believe "mistakes can be made"; and (4) multiple risk factors impacting CKD management, including clinical, social and behavioural determinants. CONCLUSIONS: The high prevalence of CKD and reliance on digital health systems in remote primary health settings can make a clinical decision support system valuable for supporting clinicians who may not have extensive experience in managing medicines for people with CKD.

Pharmacists as patient advocates: A series of case studies illustrating the impacts of a regular pharmacist service in residential aged care (nursing homes).

Background: Medicine-related problems are common in older people living in residential aged care facilities (RACFs). Recognising the significant medicine-related problems, the Australian government has announced a $345 million funding package to employ on-site pharmacists in RACFs starting in 2023. The new on-site pharmacists are to provide a range of clinical services to reduce medicine-related adverse events, promote quality use of medicines, and improve clinical governance and education. Underpinning these services, the authors argue that pharmacists play the critical role as resident advocates. Objective: This study aims to demonstrate how pharmacists can enhance their advocacy responsibility within and beyond the clinical environment to not only reduce medicine-related adverse events but also improve residents' overall health and quality of life. Methods: This study uses a case series methodology to demonstrate pharmacists' diverse roles in advocating for residents and their families. The case studies were based on participants enrolled in the Reducing Medicine-Induced Deterioration and Adverse Reactions (ReMInDAR) trial, a randomised controlled trial testing the effects of a regular pharmacist service across the Australian RACFs. Results: Pharmacists' advocacy ranged from persistence in follow-up with a resident's general practitioner (GP) to ensure the GP was aware that a patient was experiencing bleeding and bruising while on an anticoagulant, to advocating for a new bed for a resident with peripheral oedema who had been sleeping in his chair due to fear of falling out of his current bed. Conclusions: Our trial focussed on pharmacists serving as the residents' advocate to improve their overall health and quality of life, rather than just addressing a list of medicine-related problems. The pharmacist model used in the ReMInDAR trial supports pharmacists to work to their full scope of practice, helps guide the Australian government's new on-site pharmacist program, and serves as an exemplar pharmacist in aged care model internationally.

Prevalence and Preventability of Adverse Medicine Events in a Sample of Australian Aged-Care Residents: A Secondary Analysis of Data from the ReMInDAR Trial.

BACKGROUND: Aged care residents are vulnerable to the harmful effects of medicines; however, data on the prevalence and preventability of adverse medicine events in aged care residents are scarce. AIM: To determine the prevalence and preventability of adverse medicine events in Australian aged care residents. METHODS: A secondary analysis of data from the Reducing Medicine-Induced Deterioration and Adverse Reactions (ReMInDAR) trial was conducted. Potential adverse medicine events were identified and independently screened by two research pharmacists to produce a short-list of potential adverse medicine events. An expert clinical panel reviewed each potential adverse medicine to determine the likelihood that the event was medicine related (based on the Naranjo Probability Scale criteria). The clinical panel assessed preventability of medicine-related events using Schumock-Thornton criteria. RESULTS: There were 583 adverse events due to medicines, involving 154 residents (62% of the 248 study participants). There was a median of three medication-related adverse events (interquartile range [IQR] 1-5) per resident over the 12-month follow-up period. The most common medication-related adverse events were falls (56%), bleeding (18%) and bruising (9%). There were 482 (83%) medication-related adverse events that were preventable, most commonly falls (66% of preventable adverse medicine events), bleeding (12%) and dizziness (8%). Of the 248 residents, 133 (54% of the cohort) had at least one preventable adverse medicine event, with a median of 2 (IQR 1-4) preventable adverse medicine events per resident. CONCLUSION: In total, 62% of aged care residents in our study had an adverse medicine event and 54% had a preventable adverse medicine event in a 12-month period.

Using wrist-worn accelerometers to identify the impact of medicines with anticholinergic or sedative properties on sedentary time: A 12-month prospective analysis.

INTRODUCTION: Studies have shown that use of medicines with sedative or anticholinergic properties is associated with a decline in physical function; however, the effects have not been quantified, and it is not known how and which specific physical movements are affected. This prospective study quantified the impact of a change in sedative or anticholinergic load over time on 24-hour activity composition. METHODS: This study used data collected from a randomised trial assessing an ongoing pharmacist service in residential aged care. The 24-hour activity composition of sleep, sedentary behaviour, light-intensity physical activity, and moderate to vigorous physical activity was derived from 24-hour accelerometry bands. Mixed effect linear models were used to regress the multivariate outcome of 24-hour activity composition on medication load at baseline and at 12 months. A fixed effect interaction between trial stage and medication load was included to test for differing sedative or anticholinergic load effects at the two trial stages. RESULTS: Data for 183 and 85 participants were available at baseline and 12 months respectively. There was a statistically significant interaction between medication load and time point on the multivariate outcome of 24-hour activity composition (sedative F = 7.2, p < 0.001 and anticholinergic F = 3.2, p = 0.02). A sedative load increase from 2 to 4 over the 12-month period was associated with an average increase in daily sedentary behaviour by an estimated 24 min. CONCLUSION: As sedative or anticholinergic load increased, there was an increase in sedentary time. Our findings suggest wearable accelerometry bands are a possible tool for monitoring the effects on physical function of sedative and anticholinergic medicines. TRIAL REGISTRATION: The ReMInDAR trial was registered on the Australian and New Zealand Trials Registry ACTRN12618000766213.

Precision public-health intervention for care coordination: a real-world study.

BACKGROUND: Health emergencies disproportionally affect vulnerable populations. Digital tools can help primary care providers find, and reach, the right patients. AIM: To evaluate whether digital interventions delivered directly to GPs' clinical software were more effective at promoting primary care appointments during the COVID-19 pandemic than interventions delivered by post. DESIGN AND SETTING: Real-world, non-randomised, interventional study involving GP practices in all Australian states. METHOD: Intervention material was developed to promote care coordination for vulnerable older veterans during the COVID-19 pandemic, and sent to GPs either digitally to the clinical practice software system or in the post. The intervention material included patient-specific information sent to GPs to support care coordination, and education material sent via post to veterans identified in the administrative claims database. To evaluate the impact of intervention delivery modalities on outcomes, the time to first appointment with the primary GP was measured; a Cox proportional hazards model was used, adjusting for differences and accounting for pre-intervention appointment numbers. RESULTS: The intervention took place in April 2020, during the first weeks of COVID-19 social distancing restrictions in Australia. GPs received digital messaging for 51 052 veterans and postal messaging for 26 859 veterans. The digital group was associated with earlier appointments (adjusted hazard ratio 1.38 [1.34 to 1.41]). CONCLUSION: Data-driven digital solutions can promote care coordination at scale during national emergencies, opening up new perspectives for precision public-health initiatives.

Experiences and perceptions of dementia in Vietnam and among the Vietnamese diaspora: a systematic review of qualitative studies.

Objectives: This paper aimed to review and synthesise the qualitative research evidence on the experiences and perceptions of dementia in Vietnam and among the Vietnamese diaspora.Methods: Systematic searches were conducted in June 2019 using Medline, Embase, Emcare, PsycINFO and Cochrane electronic databases, as well as grey literature. Keywords and Medical Subject Headings [MeSH terms] for dementia and associated terms were combined with keywords for Vietnam and its provinces. Qualitative research articles published in English or Vietnamese were included to examine evidence on the life experiences of Vietnamese people with dementia using thematic analysis.Results: Our searches resulted in 3,940 papers, from which 21 qualitative research studies were included for final analysis. The majority of research has not been undertaken in Vietnam but with the Vietnamese diaspora in Western countries and has taken a cultural perspective to analyses. Research in Western countries has focused on the need for culturally adapted and culturally sensitive models of care. Emerging themes about the life experiences of Vietnamese people with dementia identified from the studies included: many people do not have diagnostic terms for dementia but use the descriptive language of symptoms; stigma was a reported problem and on occasions can be observed in the descriptive language used for people with dementia; cultural and traditional values create both an opportunity and a barrier, supporting compassion, family care and relaxation, but creating barriers to accessing health services or long-term residential care.Conclusions: This is the first systematic review reporting qualitative evidence on the life experiences of people with dementia in Vietnam and among the Vietnamese diaspora. Future research is needed on the voice of people with dementia themselves and their caregivers particularly in Vietnam, and low and middle-income countries with regards to living with dementia, pathways to care from diagnosis, treatment, care and support, additional social care and preparedness for end of life care for people with dementia.

Wrist accelerometer temporal analysis as a prognostic tool for aged care residents: A sub-study of the ReMInDAR trial.

BACKGROUND: Objective measures for screening, prioritizing, and planning care for frail individuals are essential for appropriate aged care provision. This study evaluates metrics derived from actigraphy measures (captured by wrist accelerometer) as a digital biomarker to identify frail individuals at risk of adverse outcomes, including death, hospitalization, and cognitive decline. METHODS: This was a secondary study using data from a randomized controlled trial assessing the effectiveness of an ongoing pharmacist service in residential aged care facilities. Three metrics are studied and compared: the Frailty Index, the daily time spent in light time activity, and the temporal correlation of the actigraphy signal, measured by detrended fluctuation analysis. The association between actigraphy-derived metrics at baseline and adverse events within 12 months (death, cognitive decline, and hospitalizations) was assessed using logistic regression. RESULTS: Actigraphy records were available for 213 participants living in aged-care, median age of 85 years. Individuals with higher temporal correlation (activity is less random) were at lower risk of death (Standardized OR: 0.49; 95% CI 0.34, 0.7, p < 0.001) and hospitalization (Standardized OR: 0.57; 95% CI 0.42, 0.77, p < 0.001) in 12 months, but there was no difference in cognitive decline (Standardized OR: 1; 95% CI 0.74, 1.35, p = 0.98). The predictive model that included temporal correlation had an area under the curve of 0.70 (CI 0.60-0.80) for death and 0.64 (CI 0.54-0.72) for hospitalization. CONCLUSION: Temporal correlation of the actigraphy signal from aged care residents was strongly associated with death and hospitalization, but not cognitive decline. Digital biomarkers may have a place as an objective, accurate, and low-cost patient metric to support risk stratification and clinical planning.

Frailty trajectory over one year among residential aged care (nursing home) residents.

Objectives: Large population-based studies examining frailty trajectory found a linear increase in frailty over time. The pattern in which frailty changes over time for an individual person is less well-described. We examined the frailty trajectory of older adults living in aged-care in Australia. Materials and methods: This secondary study used data from a randomised controlled trial involving 39 aged-care facilities in Australia. The trial intervention was an on-going pharmacist-led intervention occurring every 8 weeks over 12 months aimed at preventing medicine-induced deterioration and adverse reactions. Frailty was assessed using the Frailty Index. Participants were categorised as non-frail, pre-frail and frail. Individual frailty trajectory over 12 months was visualised using the alluvial plot. Case notes were examined to explore reasons for any rapid transitions in frailty status. Results: A total of 248 participants was included. At baseline, 40.3% were non-frail and 59.7% were pre-frail. The proportion of participants who were non-frail and pre-frail decreased over time; 15.7% were frail at 6 months and 23.4% were frail at 12 months. Overall, twenty different combinations of frailty transitions were identified over 12 months. Retrospective analysis of case notes suggest that death or transition from non-frail to frail was often preceded by hospitalisation, falls, medication change or clinically significant deterioration in grip strength or cognition. Conclusion: The degree of frailty increased over time, but there were variations in the individual trajectories. Regular monitoring of events that precede changes in frailty status is needed to identify strategies to prevent further deterioration in residents' conditions.

Medicine-Induced Acute Kidney Injury Findings from Spontaneous Reporting Systems, Sequence Symmetry Analysis and a Case-Control Study with a Focus on Medicines Used in Primary Care.

INTRODUCTION: Primary care provides an opportunity to prevent community acquired, medicine or drug-induced acute kidney injury. One of the barriers to proactive prevention of medicine-induced kidney injury in primary care is the lack of a list of nephrotoxic medicines that are most problematic in primary care, particularly one that provides a comparison of risks across medicines. OBJECTIVE: The aim of this study was to consolidate evidence on the risks associated with medicines and acute kidney injury, with a focus on medicines used in primary care. METHOD: We searched the MEDLINE and EMBASE databases to identify published studies of all medicines associated with acute kidney injury identified from spontaneous report data. For each medicine positively associated with acute kidney injury, as identified from spontaneous reports, we implemented a sequence symmetry analysis (SSA) and a case-control design to determine the association between the medicine and hospital admission with a primary diagnosis of acute kidney injury (representing community-acquired acute kidney injury). Administrative claims data held by the Australian Government Department of Veterans' Affairs for the study period 2005-2019 were used. RESULTS: We identified 89 medicines suspected of causing acute kidney injury based on spontaneous report data and a reporting odds ratio above 2, from Japan, France and the US. Spironolactone had risk estimates of 3 or more based on spontaneous reports, SSA and case-control methods, while furosemide and trimethoprim with sulfamethoxazole had risk estimates of 1.5 or more. Positive association with SSA and spontaneous reports, but not case control, showed zoledronic acid had risk estimates above 2, while candesartan telmisartan, simvastatin, naproxen and ibuprofen all had risk estimates in SSA between 1.5 and 2. Positive associations with case-control and spontaneous reports, but not SSA, were found for amphotericin B, omeprazole, metformin, amlodipine, ramipril, olmesartan, ciprofloxacin, valaciclovir, mycophenolate and diclofenac. All with the exception of metformin and omeprazole had risk estimates above 2. CONCLUSION: This research highlights a number of medicines that may contribute to acute injury; however, we had an insufficient sample to confirm associations of some medicines. Spironolactone, furosemide, and trimethoprim with sulfamethoxazole are medicines that, in particular, need to be used carefully and monitored closely in patients in the community at risk of acute kidney injury.

Correction: Lim et al. Patient-Reported Questionnaires to Identify Adverse Drug Reactions: A Systematic Review. Int. J. Environ. Res. Public Health 2021, 18, 11877.

There was an error in the original publication [...].

Monoclonal antibodies and Fc-fusion protein biologic medicines: A multinational cross-sectional investigation of accessibility and affordability in Asia Pacific regions between 2010 and 2020.

Background: Monoclonal antibody (mAb) and Fc-fusion protein (FcP) are highly effective therapeutic biologics. We aimed to analyse consumption and expenditure trends in 14 Asia-Pacific countries/regions (APAC) and three benchmark countries (the UK, Canada, and the US). Methods: We analysed 440 mAb and FcP biological products using the IQVIA-MIDAS global sales database. For each year between 2010 and 2020 inclusive, we used standard units (SU) sold per 1000 population and manufacture level price (standardised in 2019 US dollars) to evaluate consumption (accessibility) and expenditure (affordability). Changes of consumption and expenditure were estimated using compound annual growth rate (CAGR). Correlations between consumption, country's economic and health performance indicators were measured using Spearman correlation coefficient. Findings: Between 2010 and 2020, CAGRs of consumption in each region ranged from 7% to 34% and the CAGRs of expenditure ranged from 9% to 31%. The median consumption of biologics was extremely low in lower-middle-income economies (0·29 SU/1000 population) compared with upper-middle-income economies (1·20), high-income economies (40·94) and benchmark countries (109·55), although the median CAGRs of biologics consumption in lower-middle-income economies (31%) was greater than upper-middle-income (14%), high-income economies (13%) and benchmark countries (9%). Consumption was correlated with GDP per capita [Spearman's rank correlation coefficient (r) = 0·75, p < 0·001], health expenditure as a percentage of total (r = 0·83, p < 0·001) and medical doctors' density (r = 0·85, p < 0·001). Interpretation: There have been significant increases in mAb and FcP biologics consumption and expenditure, however accessibility of biological medicines remains unequal and is largely correlated with country's income level. Funding: This research was funded by NHMRC Project Grant GNT1157506 and GNT1196900; Enhanced Start-up Fund for new academic staff and Internal Research Fund, Department of Medicine, LKS Faculty of Medicine, University of Hong Kong.

Pioglitazone use in Australia and the United Kingdom following drug safety advisories on bladder cancer risk: An interrupted time series study.

PURPOSE: National regulators in Australia and the United Kingdom issued safety advisories on the association between pioglitazone use and bladder cancer in July 2011. The Australian advisory noted that males were at higher risk of bladder cancer than females, while the UK advisory highlighted a new recommendation, suggest careful consideration in the elderly due to increasing risk with age. This study examined whether these differences in the advisories had different age- and sex-based impacts in each country. METHODS: Interrupted time series analysis was used to compare pioglitazone use (prescriptions/100000 population) in Australia and the United Kingdom for the 24 months before and 11 months after the July 2011 safety advisories (study period July 2009-June 2012). Separate models were used to compare use by sex and age group (≥65 years vs. <65 years) in each country. RESULTS: Pioglitazone use fell in Australia (17%) and the United Kingdom (24%) following the safety advisories. Use of pioglitazone fell more for males (18%) than females (16%) in Australia, and more for females (25%) than males (23%) in the United Kingdom; however, neither difference was statistically significant (Australia p = 0.445, United Kingdom p = 0.462). Pioglitazone use fell to a similar extent among older people than younger people in the United Kingdom (23% vs. 26%, p = 0.354), and did not differ between age groups in Australia (both 18%, p = 0.772). CONCLUSIONS: The results indicate that differences in the Australian and UK safety advisories resulted in substantial reductions in pioglitazone use at the population level in both countries, however, differences by sub-groups were not observed.

Hydroxyzine Initiation Following Drug Safety Advisories on Cardiac Arrhythmias in the UK and Canada: A Longitudinal Cohort Study.

INTRODUCTION: Regulatory advisories on hydroxyzine and risk of QT prolongation and Torsade de pointes (TdP) were issued in the UK in April 2015 and Canada in June 2016. We hypothesized patients with risk factors for QT prolongation and TdP, compared with those without risk factors, would be less likely to initiate hydroxyzine in the UK and in British Columbia (BC), Canada, following advisories. METHODS: We conducted a longitudinal study with repeated measures, and evaluated hydroxyzine initiation in a UK cohort and a concurrent BC control cohort (April 2013-March 2016) as well as in a BC advisory cohort (June 2014-May 2017). RESULTS: This study included 247,665 patients in the UK cohort, 297,147 patients in the BC control cohort, and 303,653 patients in the BC advisory cohort. Over a 12-month post-advisory period, hydroxyzine initiation decreased by 21% in the UK (rate ratio 0.79, 95% confidence interval 0.66-0.96) relative to the expected level of initiation based on the pre-advisory trend. Hydroxyzine initiation did not change in the BC control cohort or following the Canadian advisory in the BC advisory cohort. The decrease in hydroxyzine initiation in the UK in the 12 months after the advisories was not significantly different for patients with risk factors compared with those without risk factors. CONCLUSION: Hydroxyzine initiation decreased in the UK, but not in BC, in the 12 months following safety advisories. The decrease in hydroxyzine initiation in the UK was not significantly different for patients with versus without risk factors for QT prolongation and TdP.

Effect of an ongoing pharmacist service to reduce medicine-induced deterioration and adverse reactions in aged-care facilities (nursing homes): a multicentre, randomised controlled trial (the ReMInDAR trial).

OBJECTIVE: To assess the effectiveness of a pharmacist-led intervention using validated tools to reduce medicine-induced deterioration and adverse reactions. DESIGN AND SETTING: Multicenter, open-label parallel randomised controlled trial involving 39 Australian aged-care facilities. PARTICIPANTS: Residents on ≥4 medicines or ≥1 anticholinergic or sedative medicine. INTERVENTION: Pharmacist-led intervention using validated tools to detect signs and symptoms of medicine-induced deterioration which occurred every 8 weeks over 12 months. COMPARATOR: Usual care (Residential Medication Management Review) provided by accredited pharmacists. OUTCOMES: Primary outcome was change in Frailty Index at 12 months. Secondary outcomes included changes in cognition, 24-hour movement behaviour by accelerometry, grip strength, weight, adverse events and quality of life. RESULTS: 248 persons (median age 87 years) completed the study; 120 in the interventionand, 128 in control arms. In total 575 pharmacist, sessions were undertaken in the intervention arm. There was no statistically significant difference for change in frailty between groups (mean difference: 0.009, 95% CI: -0.028, 0.009, P = 0.320). A significant difference for cognition was observed, with a mean difference of 1.36 point change at 12 months (95% CI: 0.01, 2.72, P = 0.048). Changes in 24-hour movement behaviour, grip strength, adverse events and quality of life were not significantly different between groups. Point estimates favoured the intervention arm at 12 months for frailty, 24-hour movement behaviour and grip strength. CONCLUSIONS: The use of validated tools by pharmacists to detect signs of medicine-induced deterioration is a model of practice that requires further research, with promising results from this trial, particularly with regards to improved cognition.

The association between exacerbation of chronic obstructive pulmonary disease and timing of paracetamol use: a cohort study in elderly Australians.

BACKGROUND: In elderly populations, paracetamol may be used regularly for conditions such as osteoarthritis. Paracetamol has been associated with respiratory disease through a proposed mechanism of glutathione depletion and oxidative stress. Given that chronic obstructive pulmonary disease (COPD) is frequently co-morbid with osteoarthritis, this study investigated whether the dose and timing of paracetamol exposure may induce COPD exacerbations. METHODS: The study population was 3523 Australian Government Department of Veterans' Affairs full entitlement holders who had existing COPD on 1 January 2011, who were dispensed at least one prescription of paracetamol between 1 January 2011 and 30 September 2015, and had no paracetamol dispensed in the 6 months prior to 1 January 2011. The outcome was time to first hospitalisation for COPD exacerbation after initiation of paracetamol. A weighted cumulative exposure approach was used. RESULTS: The association between paracetamol exposure and COPD exacerbation was protective or harmful depending on the dose, duration, and recency of exposure. Compared to non-use, current use at the maximum dose of 4 g daily for 7 days was associated with a lower risk (HR = 0.78, 95% CI = 0.67-0.92) and a higher risk after 30 days (HR = 1.27, 95% CI = 1.06-1.52). Risk declined to baseline after 2 months. For past use, there was a short-term increase in risk on discontinuation depending of dose, duration and time since stopping. CONCLUSIONS: Patients and doctors should be aware of the possible risk of COPD exacerbation with higher dose paracetamol 1 to 6 weeks after initiation or discontinuation, but no increased risk after 2 months.