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.

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.

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.

Potentially inappropriate prescribing in people with dementia: An Australian population-based study.

OBJECTIVE: To investigate the prevalence of potentially inappropriate prescribing (PIP) using the Screening Tool of Older Person's Prescriptions (STOPP) criteria in people with dementia compared with people without dementia. METHODS: A retrospective cohort study was conducted using the Pharmaceutical Benefits Scheme 10% sample of pharmacy claims. People with dementia were defined as those dispensed a medicine for dementia (cholinesterase inhibitors, memantine, or risperidone for behavioural and psychological symptoms of dementia) between 1 January 2005 and 31 December 2015, aged 65 years or older at 1 January 2016 and alive at the end of 2016. An age- and gender-matched comparison cohort of people not dispensed medicines for dementia was identified. PIP prevalence was determined between 1 January 2016 and 31 December 2016. RESULTS: In total, 8280 people dispensed medicines for dementia and 41 400 comparisons not dispensed medicines for dementia were included: 63% were female and the median age was 82 years. PIP prevalence was 79% among people with dementia compared with 70% among the comparison group (P < .0001). Use of anticholinergics, long-term use of high-dose proton pump inhibitors, and use of benzodiazepines were the most common instances of PIP in people with dementia. After adjustments for age, gender, comorbidity, and number of prescribers, people with dementia were more likely to be exposed to PIP than comparisons (adjusted OR 1.44, 95% CI, 1.35-1.53, P < .0001). CONCLUSIONS: PIP was more common in people dispensed medicines for dementia than comparisons. These results highlight the need for effective interventions to optimize prescribing in people with dementia.

Antipsychotic polypharmacy in older Australians.

ABSTRACTBackground:Antipsychotics are commonly used, and the rate of use is highest, among those aged 65 years or over, where the risk of adverse events is also high. Up to 20% of younger adults use more than one antipsychotic concurrently; however there are few studies on the prevalence of antipsychotic polypharmacy in older people. We aimed to analyze antipsychotic use in elderly Australians, focusing on the prevalence of antipsychotic polypharmacy and the use of medicines to manage adverse events associated with antipsychotics. METHODS: A cross-sectional study was conducted using Australian Department of Veterans' Affairs (DVA) administrative claims data for the period 1 March 2014 to 30 June 2014. Veterans dispensed at least one antipsychotic medicine during the study period was included. We determined the number of participants dispensed antipsychotic polypharmacy and the number of participants dispensed medicines to manage antipsychotic side effects. RESULTS: There were 7,412 participants with a median age of 86 years. Fifty-one percent (n=3,784) were women and 48% (n=3,569) lived in residential aged-care. Fifty one participants (0.7%) were dispensed anticholinergic medicines indicated for the management of antipsychotic-associated extrapyramidal movement disorders and eight (0.1%) were dispensed medicines for the management of hyperprolactinemia. Five percent of participants (n=365) received dual antipsychotics. Dual antipsychotic users were more likely to be under the care of a psychiatrist or to have had a mental health hospitalization than those using a single antipsychotic. CONCLUSIONS: Antipsychotic polypharmacy occurred in one in 20 elderly persons, indicating that there is room for improvement in antipsychotic use in elderly patients.

Reducing hypnotic use in insomnia management among Australian veterans: results from repeated national interventions.

BACKGROUND: The Australian Government Department of Veterans' Affairs (DVA) Veterans' Medicines Advice and Therapeutics Education Services (Veterans' MATES) programme conducted two intervention (March 2009, follow-up intervention June 2012) both of which aimed to reduce hypnotic use among Australian veterans. We evaluated the effectiveness of the interventions, and estimated the associated health consequences. METHODS: Both interventions targeted veterans who had been dispensed hypnotics prior to the intervention. Patient-specific prescriber feedback containing patient details and the volume of hypnotics dispensed, along with tailored educational information, was mailed to general practitioners. Veterans, pharmacists and directors of care in residential aged care facilities were mailed tailored educational information. Interrupted time-series and segmented regression modelling were used to determine the effect of the two interventions on the rate of hypnotics dispensing. The cumulative patient-months of hypnotic treatment avoided as a result of the interventions was calculated. We estimated improvements in health consequences of as a result of hypnotic treatment avoided based on the results of cohort studies in the same population identifying the association between hypnotic and sedative use on the outcomes of falls, and confusion. RESULTS: After the first Veterans' MATES intervention in March 2009, hypnotic use declined by 0.2% each month, when compared to the baseline level (p = 0.006). The intervention effect was attenuated after one year, and use of hypnotics was found to increase by 0.2% per month after March 2010. Following the second intervention in June 2012, there was a further significant decline in use of 0.18% each month over the 12 months of follow up (p = 0.049). The cumulative effect of both interventions resulted in 20,850 fewer patient-months of treatment with hypnotics. This cumulative reduction in hypnotic use was estimated to lead to a minimum of 1 fewer hospital admissions for acute confusion and 7 fewer hospital admissions due to falls. CONCLUSIONS: The Veterans' MATES insomnia interventions which involved multiple stakeholders were effective in reducing hypnotic use among older Australians. Repetition of key messages led to sustained practice change.

Preoperative medication use and postoperative delirium: a systematic review.

BACKGROUND: Medications are frequently reported as both predisposing factors and inducers of delirium. This review evaluated the available evidence and determined the magnitude of risk of postoperative delirium associated with preoperative medication use. METHODS: A systematic search in Medline and EMBASE was conducted using MeSH terms and keywords for postoperative delirium and medication. Studies which included patients 18 years and older who underwent major surgery were included. The methodological quality of included studies was assessed independently by two authors using the Newcastle-Ottawa quality assessment scale for cohort studies. RESULTS: Twenty-nine studies; 25 prospective cohort, three retrospective cohort and one post hoc analysis of RCT data were included. Only four specifically aimed to assess medicines as an independent predictor of delirium, all other studies included medicines among a number of potential predictors of delirium. Of the studies specifically testing the association with a medication class, preoperative use of beta-blockers (OR = 2.06[1.18-3.60]) in vascular surgery and benzodiazepines RR 2.10 (1.23-3.59) prior to orthopedic surgery were significant. However, evidence is from single studies only. Where medicines were included as one possible factor among many, hypnotics had a similar risk estimate to the benzodiazepine study, with one significant and one non-significant result. Nifedipine use prior to cardiac surgery was found to be significantly associated with delirium. The non-specific grouping of psychoactive medication use preoperatively was generally higher with an associated two-to-seven-fold higher risk of postoperative delirium, while only two studies included narcotics without other agents, with one significant and one non-significant result. CONCLUSIONS: There was a limited number of high quality studies in the literature quantifying the direct association between preoperative medication use and postsurgical delirium. More studies are required to evaluate the association of specific preoperative medications on the risk of postoperative delirium so that comprehensive guidelines for medicine use prior to surgery can be developed to aid delirium prevention. TRIAL REGISTRATION: This systematic review has been registered on PROSPERO International prospective register of systematic reviews (Registration number: CRD42016051245 ).

Use of proton pump inhibitors among older Australians: national quality improvement programmes have led to sustained practice change.

OBJECTIVE: To evaluate the impact of national multifaceted initiatives to improve use of proton pump inhibitors (PPIs) on the use of PPIs among older Australians. DESIGN: Interrupted time series analysis using administrative health claims data from the Australian Government Department of Veterans' Affairs (DVA). SETTING: Australia. PARTICIPANTS: All veterans and dependents who received PPIs between January 2003 and December 2013. INTERVENTION(S): National, multifaceted interventions to improve PPI use were conducted by the Australian Government Department of Veterans' Affairs Veterans' MATES programme and Australia's NPS MedicineWise in April 2004, June 2006, May 2009 and August 2012. MAIN OUTCOME MEASURE(S): Trends in monthly rate of use of any PPI among the veteran population, and the monthly rate of use of low strength PPIs among all veterans dispensed a PPI. RESULTS: Interventions in 2004, 2006, 2009 and 2012 slowed the rate of increase in PPI use significantly, with the 2012 intervention resulting in a sustained 0.04% decrease in PPI use each month. The combined effect of all four interventions was a 20.9% (95% CI 7.8-33.9%) relative decrease in PPI use 12 months after the final intervention. The four interventions also resulted in a 42.2% (95% CI 19.9-64.5%) relative increase in low strength PPI use 12 months after the final intervention. CONCLUSIONS: National multifaceted programmes targeting clinicians and consumers were effective in reducing overall PPI use and increasing use of low strength PPIs. Interventions to improve PPI use should incorporate regular repetition of key messages to sustain practice change.

Suboptimal medication-related quality of care preceding hospitalisation of older patients.

OBJECTIVE: To examine the prevalence of suboptimal medication-related processes of care before the hospitalisation of older patients. DESIGN AND SETTING: We conducted a retrospective cohort study using a clinical indicator set related to medication management that has been validated by an expert panel as consisting of suboptimal aspects of medication use that clinicians should be able to foresee and avoid. Australian Government Department of Veterans' Affairs administrative claims data between 1 July 2007 and 30 June 2012 were analysed according to these clinical indicators to assess medication-related processes of care preceding hospitalisation. PARTICIPANTS: Veterans with one or more hospitalisations in Australia for a condition defined by the clinical indicator set. MAIN OUTCOME MEASURE: Prevalence of suboptimal medication-related processes of care before hospitalisation as a proportion of all hospitalisations defined by diagnoses in the clinical indicator set. RESULTS: During the 5-year study period, there were 164,813 hospitalisations with primary diagnoses for conditions included in the clinical indicator set, encompassing 83,430 patients. The overall proportion of hospitalisations that were preceded by suboptimal medication-related processes of care was 25.2% (41,546 hospitalisations); 34.5% of patients (28,807 patients) had at least one hospitalisation and 10.4% (8640 patients) had two or more hospitalisations preceded by suboptimal medication-related processes of care. At least one in 10 hospitalisations for chronic heart failure, ischaemic stroke, asthma, gastrointestinal ulcer or bleeding, fracture, renal failure or nephropathy, hyperglycaemia or hypoglycaemia were preceded by suboptimal medication-related processes of care. CONCLUSIONS: This study highlights conditions for which there are evidence-practice gaps in medication management in the older population. Routine prospective monitoring of these evidence-based, validated, medication-related clinical indicators provides a means for quality improvement in the management of common chronic conditions.

An international comparison of spontaneous adverse event reports and potentially inappropriate medicine use associated with dabigatran.

PURPOSE: The objective of this study was to analyse spontaneous adverse event (SAE) reports associated with the oral anticoagulant dabigatran from Australia, Canada and USA and to examine concomitant medicine use. METHODS: Spontaneous adverse event national databases from Australia, Canada and the USA were used to examine all reports of adverse events associated with dabigatran from 1st August 2005 to 31st March 2013. Disproportionality analysis was conducted for the quantitative detection of signals using the USA database. Concomitant medicine use was examined to identify potentially inappropriate medicines, which may place the patient at increased risk for adverse events. RESULTS: There were a total of 1039, 1333 and 13 788 SAE reports associated with dabigatran from Australia, Canada and USA, respectively. Gastrointestinal (GI) disorders were the most commonly reported adverse event, ranging from 27.5% for Australia and up to 40.5% for USA. Of these, GI haemorrhage accounted for 81.5% of Australian, 71.5% of Canadian and 42% of the USA adverse event reports for GI disorders. Positive signals were confirmed in the USA data (GI haemorrhage; PRR 18.18, χ2 40993.51 and ROR 19.55 95% CI 18.77-20.36). Use of concomitant medicines with the potential to increase bleeding risk across all three countries ranged from 34.1% for Australia to 51.1% for the USA. CONCLUSIONS: A large proportion of adverse events were associated with concomitant therapies, which may have placed the patient at increased risk of harm. This highlights the need for pharmacovigilance by the prescribing clinician to minimise risk and ensure the safe and effective integration of dabigatran into routine clinical practice.

Bridging evidence-practice gaps: improving use of medicines in elderly Australian veterans.

BACKGROUND: The Australian Government Department of Veterans' Affairs (DVA) funds an ongoing health promotion based program to improve use of medicines and related health services, which implements interventions that include audit and feedback in the form of patient-specific feedback generated from administrative claims records. We aimed to determine changes in medicine use as a result of the program. METHODS: The program provides targeted patient-specific feedback to medical practitioners. The feedback is supported with educational material developed by a clinical panel, subject to peer review and overseen by a national editorial committee. Veterans who meet target criteria also receive educational brochures. The program is supported by a national call centre and ongoing national consultation. Segmented regression analyses (interrupted time series) were undertaken to assess changes in medication use in targeted veterans pre and post each intervention. RESULTS: 12 interventions were included; three to increase medicine use, seven which aimed to reduce use, and two which had combination of messages to change use. All programs that aimed to increase medicine use were effective, with relative effect sizes at the time of the intervention ranging from 1% to 8%. Mixed results were seen with programs aiming to reduce inappropriate medicine use. Highly specific programs were effective, with relative effect sizes at the time of the intervention of 10% decline in use of NSAIDs in high risk groups and 14% decline in use of antipsychotics in dementia. Interventions targeting combinations of medicines, including medicine interactions and potentially inappropriate medicines in the elderly did not change practice significantly. Interventions with combinations of messages targeting multiple components of practice had an impact on one component, but not all components targeted. CONCLUSIONS: The Veterans' MATES program showed positive practice change over time, with interventions increasing use of appropriate medicines where under-use was evident and reduced use of inappropriate medicines when single medicines were targeted. Combinations of messages were less effective, suggesting specific messages focusing on single medicines are required to maximise effect. The program provides a model that could be replicated in other settings.

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.

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.

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.

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.

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.

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.