Innovations in pharmacovigilance studies of medicines in older people.

Pharmacovigilance is defined by the World Health Organization as "the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine/vaccine related problem". Pharmacovigilance studies are critical for detecting and assessing adverse events of medicines that may not have been observed in clinical trials. This activity is especially important in older people who are often excluded from clinical trials as they have multiple chronic conditions and use multiple medicines for longer durations than the clinical trials. In this narrative review we describe innovative methods in pharmacovigilance studies of medicines in older people that leverage the increasing availability of digital health technologies, electronic health records and real-world health data to identify and quantify medication related harms in older people.

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.

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.

A comparison of survival models for prediction of eight-year revision risk following total knee and hip arthroplasty.

BACKGROUND: There is increasing interest in the development and use of clinical prediction models, but a lack of evidence-supported guidance on the merits of different modelling approaches. This is especially true for time-to-event outcomes, where limited studies have compared the vast number of modelling approaches available. This study compares prediction accuracy and variable importance measures for four modelling approaches in prediction of time-to-revision surgery following total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: The study included 321,945 TKA and 151,113 THA procedures performed between 1 January 2003 and 31 December 2017. Accuracy of the Cox model, Weibull parametric model, flexible parametric model, and random survival forest were compared, with patient age, sex, comorbidities, and prosthesis characteristics considered as predictors. Prediction accuracy was assessed using the Index of Prediction Accuracy (IPA), c-index, and smoothed calibration curves. Variable importance rankings from the Cox model and random survival forest were also compared. RESULTS: Overall, the Cox and flexible parametric survival models performed best for prediction of both TKA (integrated IPA 0.056 (95% CI [0.054, 0.057]) compared to 0.054 (95% CI [0.053, 0.056]) for the Weibull parametric model), and THA revision. (0.029 95% CI [0.027, 0.030] compared to 0.027 (95% CI [0.025, 0.028]) for the random survival forest). The c-index showed broadly similar discrimination between all modelling approaches. Models were generally well calibrated, but random survival forest underfitted the predicted risk of TKA revision compared to regression approaches. The most important predictors of revision were similar in the Cox model and random survival forest for TKA (age, opioid use, and patella resurfacing) and THA (femoral cement, depression, and opioid use). CONCLUSION: The Cox and flexible parametric models had superior overall performance, although all approaches performed similarly. Notably, this study showed no benefit of a tuned random survival forest over regression models in this setting.

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.

Implementation and Evaluation of a Digitally Enabled Precision Public Health Intervention to Reduce Inappropriate Gabapentinoid Prescription: Cluster Randomized Controlled Trial.

BACKGROUND: Digital technologies can enable rapid targeted delivery of audit and feedback interventions at scale. Few studies have evaluated how mode of delivery affects clinical professional behavior change and none have assessed the feasibility of such an initiative at a national scale. OBJECTIVE: The aim of this study was to develop and evaluate the effect of audit and feedback by digital versus postal (letter) mode of delivery on primary care physician behavior. METHODS: This study was developed as part of the Veterans' Medicines Advice and Therapeutics Education Services (MATES) program, an intervention funded by the Australian Government Department of Veterans' Affairs that provides targeted education and patient-specific audit with feedback to Australian general practitioners, as well as educational material to veterans and other health professionals. We performed a cluster randomized controlled trial of a multifaceted intervention to reduce inappropriate gabapentinoid prescription, comparing digital and postal mode of delivery. All veteran patients targeted also received an educational intervention (postal delivery). Efficacy was measured using a linear mixed-effects model as the average number of gabapentinoid prescriptions standardized by defined daily dose (individual level), and number of veterans visiting a psychologist in the 6 and 12 months following the intervention. RESULTS: The trial involved 2552 general practitioners in Australia and took place in March 2020. Both intervention groups had a significant reduction in total gabapentinoid prescription by the end of the study period (digital: mean reduction of 11.2%, P=.004; postal: mean reduction of 11.2%, P=.001). We found no difference between digital and postal mode of delivery in reduction of gabapentinoid prescriptions at 12 months (digital: -0.058, postal: -0.058, P=.98). Digital delivery increased initiations to psychologists at 12 months (digital: 3.8%, postal: 2.0%, P=.02). CONCLUSIONS: Our digitally delivered professional behavior change intervention was feasible, had comparable effectiveness to the postal intervention with regard to changes in medicine use, and had increased effectiveness with regard to referrals to a psychologist. Given the logistical benefits of digital delivery in nationwide programs, the results encourage exploration of this mode in future interventions.

The Risk of Preoperative Central Nervous System-Acting Medications on Delirium Following Hip or Knee Surgery: A Matched Case-Control Study.

INTRODUCTION: Medicines acting on the central nervous system can increase the risk of postoperative delirium, but the specific medicines associated with greatest risk remain unclear. OBJECTIVES: We aimed to examine the risk of individual central nervous system-acting medicines used preoperatively on delirium after hip or knee surgery. METHODS: A matched case-control study was conducted using data from the Australian Government Department of Veterans' Affairs. We included people aged 65 years or older who had knee or hip surgery between 2000 and 2019. People with hip or knee surgery who developed postoperative delirium were cases and controls were people with hip or knee surgery but who did not develop postoperative delirium. Use of medicines including anxiolytics, sedatives, and hypnotics, opioid analgesics and antidepressants prior to surgery was compared between cases and controls. RESULTS: A total of 2614 patient cases with postoperative delirium were matched by same sex, age (±2 years), and year of admission (±2 years) with 7842 controls without postoperative delirium. Cases were more likely to be exposed to nitrazepam (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.24-2.64), sertraline (OR = 1.50, 95% CI 1.20-1.87), mirtazapine (OR = 1.38, 95% CI 1.11-1.74), venlafaxine (OR = 1.42, 95% CI 1.02-1.98), citalopram (OR = 1.54, 95% CI 1.19-1.99), escitalopram (OR = 1.42, 95% CI 1.06-1.89) or fluvoxamine (OR = 5.01, 95% CI 2.15-11.68) prior to surgery than controls. At the class level, exposure to benzodiazepines (OR = 1.20, 95% CI 1.05-1.37) and antidepressants (OR = 1.64, 95% CI 1.47-1.83) prior to surgery was significantly higher in cases than in controls. The numbers needed to treat to harm for one additional delirium case were 43 for sertraline, 40 for citalopram, 57 for mirtazapine and 26 for nitrazepam. Whereas, the numbers needed to treat to harm were found to be 20 for sertraline, 17 for citalopram, 19 for mirtazapine and 10 for nitrazepam in the 85 years or older age group, indicating that the harmful effect of these medicines is pronounced as age advances. CONCLUSIONS: People who developed delirium following hip or knee surgery were more likely to be exposed to nitrazepam, sertraline, mirtazapine, venlafaxine, citalopram, escitalopram or fluvoxamine at the time of admission for surgery. Planning to reduce use of these medicines well prior to surgery may decrease the risk of postoperative delirium.

Evaluation of Renal Function Testing in Older Australian Veterans Dispensed Medicines that Require Renal Function Monitoring.

INTRODUCTION: Renal function testing should be performed prior to initiating medicines that require dose adjustment in renal impairment, with ongoing monitoring in continued use, particularly in older people. There is little evidence regarding the extent to which renal function monitoring is performed in older Australians dispensed medicines requiring renal function monitoring. OBJECTIVE: The aim of this study was to determine the extent of renal function testing in older people dispensed medicines requiring renal function monitoring. METHODS: A retrospective analysis of administrative claims data from the Australian Government Department of Veterans' Affairs was conducted for people aged 65 years or older who were dispensed one or more medicines requiring renal function monitoring, from 1 June 2019 to 30 September 2019, to investigate the proportion of people with a claim for a pathology test that included creatinine levels in the 6-12 months before or after dispensing of a medicine requiring renal function monitoring. RESULTS: There were 100,113 people who were dispensed at least one medicine requiring renal function monitoring during the study period, of whom 15% had a history of renal impairment and 16% had diabetes mellitus. Sixty-one percent had a claim for a test in the prior 6 months; this increased to 80% of participants with a claim for a test in the prior 12 months. The rate of claims for testing was lower in aged care facility residents compared with people living in the community (54% vs 62% in the previous 6 months; p < 0.001), and was higher in people with diabetes (75% vs 58%; p < 0.001), history of renal impairment (91% vs 59%; p < 0.001) or heart failure (77% vs 60%; p < 0.001) compared with those without these conditions. CONCLUSION: Medicines that require renal function monitoring are commonly used in older Australians, and while the majority have claims for tests that include renal function, some are missing out.

Medication-related hospital admissions in aged care residents.

OBJECTIVE: To determine the prevalence of medication-related hospitalisations preceded by potentially suboptimal processes of care in aged care residents. METHOD: We conducted a retrospective analysis of administrative claims data from the Australian Government Department of Veterans' Affairs (DVA). We identified all hospital admissions for aged care residents between 1 July 2014 and 30 June 2019. The proportion of hospital admissions preceded by potentially suboptimal medication-related processes of care was determined. RESULTS: A total of 18 874 hospitalisations were included, and 46% were preceded by potentially suboptimal medication-related care. One-quarter of fracture admissions occurred in residents at risk of fracture who were not using a medicine to prevent fracture, and 87% occurred in residents using falls-risk medicines. Thirty per cent of heart failure admissions occurred in patients who were not using an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. CONCLUSION: Nearly half of hospital admissions were preceded by potentially suboptimal medication-related processes of care. Interventions to improve use of medicines for aged care residents in these areas are warranted.

The effects of anticholinergic medications on cognition in children: a systematic review and meta-analysis.

Cognitive side effects of anticholinergic medications in older adults are well documented. Whether these poor cognitive outcomes are observed in children has not been systematically investigated. We aimed to conduct a systematic review and meta-analysis on the associations between anticholinergic medication use and cognitive performance in children. Systematic review was conducted using Medline, PsychInfo, and Embase, identifying studies testing cognitive performance relative to the presence versus absence of anticholinergic medication(s) in children. We assessed effects overall, as well as relative to drug class, potency (low and high), cognitive domain, and duration of administration. The systematic search identified 46 articles suitable for meta-analysis. For the most part, random effects meta-analyses did not identify statistically significant associations between anticholinergic exposure and cognitive performance in children; the one exception was a small effect of anticholinergic anti-depressants being associated with better cognitive function (Hedges' g = 0.24, 95% CI 0.06-0.42, p = 0.01). Anticholinergic medications do not appear to be associated with poor cognitive outcomes in children, as they do in older adults. The discrepancy in findings with older adults may be due to shorter durations of exposure in children, differences in study design (predominantly experimental studies in children rather than predominantly epidemiological in older adults), biological ageing (e.g. blood brain barrier integrity), along with less residual confounding due to minimal polypharmacy and comorbidity in children.

Impact of a patient-specific national programme aimed at increasing the use of emollient moisturisers to reduce the risk of skin tears: a longitudinal cohort study.

OBJECTIVES: To evaluate the impact of a patient-specific national programme targeting older Australians and health professionals that aimed to increase use of emollient moisturisers to reduce to the risk of skin tears. DESIGN: A prospective cohort intervention. PARTICIPANTS: The intervention targeted 52 778 Australian Government's Department of Veterans' Affairs patients aged over 64 years who had risk factors for wound development, and their general practitioners (GPs) (n=14 178). OUTCOME MEASURES: An interrupted time series model compared the rate of dispensing of emollients in the targeted cohort before and up to 23 months after the intervention. Commitment questions were included in self-report forms. RESULTS: In the first month after the intervention, the rate of claims increased 6.3-fold (95% CI: 5.2 to 7.6, p<0.001) to 10 emollient dispensings per 1000 patients in the first month after the intervention. Overall, the intervention resulted in 10 905 additional patient-months of treatment. The increased rate of dispensing among patients who committed to talking to their GP about using an emollient was six times higher (rate ratio: 6.2, 95% CI: 4.4 to 8.7) than comparison groups. CONCLUSIONS: The intervention had a sustained effect over 23 months. Veterans who responded positively to commitment questions had higher uptake of emollients than those who did not.

Determinants of usefulness in professional behaviour change interventions: observational study of a 15-year national program.

OBJECTIVE: Educational, and audit and feedback interventions are effective in promoting health professional behaviour change and evidence adoption. However, we lack evidence to pinpoint which particular features make them most effective. Our objective is to identify determinants of quality in professional behaviour change interventions, as perceived by participants. DESIGN: We performed a comparative observational study using data from the Veterans' Medicines Advice and Therapeutics Education Services program, a nation-wide Australian Government Department of Veterans' Affairs funded program that provides medicines advice and promotes physician adoption of best practices by use of a multifaceted intervention (educational material and a feedback document containing individual patient information). SETTING: Primary care practices providing care to Australian veterans. PARTICIPANTS: General practitioners (GPs) targeted by 51 distinct behaviour change interventions, implemented between November 2004 and June 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: We extracted features related to presentation (number of images, tables and characters), content (polarity and subjectivity using sentiment analysis, number of external links and medicine mentions) and the use of five behaviour change techniques (prompt/cues, goal setting, discrepancy between current behaviour and goal, information about health consequences, feedback on behaviour). The main outcome was perceived usefulness, extracted from postintervention survey. RESULTS: On average, each intervention was delivered to 9667 GPs. Prompt and goal setting strategies in the audit and feedback were independently correlated to perceived usefulness (p=0.030 and p=0.005, respectively). The number of distinct behaviour change techniques in the audit and feedback was correlated with improved usefulness (Pearson's coefficient 0.45 (0.19, 0.65), p=0.001). No presentation or content features in the educational material were correlated with perceived usefulness. CONCLUSIONS: The finding provides additional evidence encouraging the use of behaviour change techniques, in particular prompt and goal setting, in audit and feedback interventions.

Use of health and support services by people living with dementia in the community setting.

OBJECTIVE: To determine the access to and use of health-care services by people with dementia in the community. METHODS: A retrospective cross-sectional analysis of the Australian Government Department of Veterans' Affairs (DVA) administrative claims data was conducted. Veterans and their spouses with one or more dementia claims between 1 January 2000 and 30 June 2016, who were aged ≥45 years at the time of the claim and who were still alive and living in the community on 30 June 2017, were included. We assessed the proportions of people with dementia who received medical, pharmacy and medicines, allied health services, and home care supports from 1 July 2016 to 30 June 2017. RESULTS: A total of 10 171 people with dementia were included. They had a median age of 89 years, 60% were female, and 63% lived in a major city. Over the one-year study period, 98% visited the GP and 99% had medicines dispensed at a pharmacy. Eighty-two per cent saw a specialist, and 19% saw a geriatrician. Thirty-one per cent received a DVA-funded dose administration aid to support medication administration, and 19% received a home medicines review. Less than half had claims for occupational therapist services (48%), community nursing (48%), physiotherapists (41%) or dentist visits (33%). Fifty-eight per cent received home care supports, for example domestic assistance. CONCLUSIONS: Many people living with dementia in the community do not access all of the health-care or support services available to them. Ensuring that people with dementia and their carers are supported to access the services available to assist them live in the community setting for as long as possible is important.

Use of analgesics following rescheduling of codeine in Australia: An interrupted time series analysis in the veteran population.

BACKGROUND: The Australian medicines regulator, the Therapeutic Goods Administration (TGA), rescheduled all codeine-containing medicines to be available only on prescription on 1 February 2018. This study was conducted to determine whether use of analgesics changed following codeine re-scheduling to prescription only status, and whether there was a change in the use of codeine preparations and a therapeutic shift to stronger opioids or other analgesics in the Australian veteran population following the change. METHODS: Interrupted time series analysis using Repatriation Pharmaceutical Benefits Scheme (RPBS) claims data from the Australian Government Department of Veterans' Affairs (DVA) for clients with dispensing of opioid and non-opioid analgesics between January 2015 and April 2019. Trends in the monthly rate of analgesic dispensings (opioid and non-opioid) were compared for the period between January 2015 and January 2018 with the period February 2018 to April 2019. RESULTS: Paracetamol with codeine 8mg was the only analgesic with an increased rate of dispensing following the February 2018 codeine scheduling changes. Prior to codeine re-scheduling, the rate of dispensing of paracetamol with codeine 8mg was decreasing by 0.9% each month. Immediately after the scheduling changes, dispensing of paracetamol with codeine 8mg increased by 45% (95%CI=1.282-1.676, p<0.001) and in the fifteen month period thereafter (February 2018 to April 2019), the rate of dispensing increased by 4% each month (95%CI=1.027-1.054, p<0.001). Therapeutic shift from over-the-counter codeine products to other opioids was not observed, with no increase in the rate of dispensing of any of the other opioid (or non-opioid) analgesics following the codeine scheduling changes. CONCLUSION: A significant increase in prescription use of paracetamol with codeine 8mg was observed after the February 2018 codeine re-scheduling. Therapeutic shift to stronger opioid analgesics was not observed in the study population.

Potentially inappropriate medication use and related hospital admissions in aged care residents: The impact of dementia.

AIMS: To determine the prevalence of potentially inappropriate medication (PIM) use at hospital admission and discharge, and the contribution to hospital admission among residential aged care facility residents with and without dementia. METHODS: We conducted a secondary analysis using data from a multihospital prospective cohort study involving consecutively admitted older adults, aged 75 years or older, who were taking 5 or more medications prior to hospital admission and discharged to a residential aged care facility in South Australia. PIM use was identified using the 2015 Screening Tool for Older Persons' Prescription and 2019 Beers criteria. An expert panel of clinicians with geriatric medicine expertise evaluated the contribution of PIM to hospital admission. RESULTS: In total, 181 participants were included, the median age was 87.5 years and 54.7% were female. Ninety-one (50.3%) had a diagnosis of dementia. Participants with dementia had fewer PIMs, according to at least 1 of the 2 screening criteria, than those without dementia, at admission (dementia: 76 [83.5%] vs no dementia: 84 [93.3%], P = .04) and discharge (78 [85.7%] vs 83 [92.2%], P = .16). PIM use was causal or contributory to the admission in 28.1% of study participants (n = 45) who were taking at least 1 PIM at admission. CONCLUSIONS: Over 80% of acutely admitted older adults took PIMs at hospital admission and discharge and for over a quarter of these people the admissions were attributable to PIM use. Hospitalisation presents an opportunity for comprehensive medication reviews, and targeted interventions that enhance such a process could reduce PIM use and related harm.

Comorbidities in an Australian sample of chronic and new opioid users.

INTRODUCTION AND AIMS: Mental health disorders and substance abuse are risk factors that both precede and follow chronic opioid use. We predicted that incident opioid users would have lower rates of mental health comorbidities than chronic opioid users, but that incident chronic opioid users would have lower rates of mental health comorbidities than prevalent chronic users. DESIGN AND METHODS: We used administrative health claims data to evaluate differences in lifetime mental health and substance abuse comorbidity profiles of people who were prevalent and incident chronic opioid users, as well as those who used opioids acutely. Results were stratified by age. RESULTS: Over 5,188 people were prevalent chronic opioid users at study entry. Of the 10,079 people who initiated opioids, 10.2 per-cent had a subsequent chronic episode (incident chronic) and the remainder stopped within 90 days (incident acute). In prevalent chronic users compared to incident chronic users, rates of depression and anxiety were higher across all age groups (odds ratio (OR) across age groups range from = 1.60, 95 percent confidence interval (CI) = 1.35,1.89, to OR = 6.66, 95 percent CI = 3.02, 14.69) and prevalence of alcohol abuse was higher in those aged 55 to 74 years (OR = 5.11, 95 percent CI = 1.83, 14.24, p = 0.002). Acute users were less likely than incident chronic users to have depression and anxiety in those aged over 74 years (depression OR = 0.82, 95 per-cent CI = 0.70, 0.95; anxiety OR = 0.82, 95% CI 0.70, 0.98). CONCLUSIONS: Mental health morbidities commonly associated with chronic opioid use increase in prevalence as chronic use continues.

Reducing medicine-induced deterioration and adverse reactions (ReMInDAR) trial: study protocol for a randomised controlled trial in residential aged-care facilities assessing frailty as the primary outcome.

INTRODUCTION: Many medicines have adverse effects which are difficult to detect and frequently go unrecognised. Pharmacist monitoring of changes in signs and symptoms of these adverse effects, which we describe as medicine-induced deterioration, may reduce the risk of developing frailty. The aim of this trial is to determine the effectiveness of a 12-month pharmacist service compared with usual care in reducing medicine-induced deterioration, frailty and adverse reactions in older people living in aged-care facilities in Australia. METHODS AND ANALYSIS: The reducing medicine-induced deterioration and adverse reactions trial is a multicentre, open-label randomised controlled trial. Participants will be recruited from 39 facilities in South Australia and Tasmania. Residents will be included if they are using four or more medicines at the time of recruitment, or taking more than one medicine with anticholinergic or sedative properties. The intervention group will receive a pharmacist assessment which occurs every 8 weeks. The pharmacists will liaise with the participants' general practitioners when medicine-induced deterioration is evident or adverse events are considered serious. The primary outcome is a reduction in medicine-induced deterioration from baseline to 6 and 12 months, as measured by change in frailty index. The secondary outcomes are changes in cognition scores, 24-hour movement behaviour, grip strength, weight, percentage robust, pre-frail and frail classification, rate of adverse medicine events, health-related quality of life and health resource use. The statistical analysis will use mixed-models adjusted for baseline to account for repeated outcome measures. A health economic evaluation will be conducted following trial completion using data collected during the trial. ETHICS AND DISSEMINATION: Ethics approvals have been obtained from the Human Research Ethics Committee of University of South Australia (ID:0000036440) and University of Tasmania (ID:H0017022). A copy of the final report will be provided to the Australian Government Department of Health. TRIAL REGISTRATION NUMBER: Australian and New Zealand Trials Registry ACTRN12618000766213.