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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. Refereed/Peer-reviewed

Aims The aim of this study was to estimate the 90-day periprosthetic joint infection (PJI) rates following total knee arthroplasty (TKA) and total hip arthroplasty (THA) for osteoarthritis (OA). Methods This was a data linkage study using the New South Wales (NSW) Admitted Patient Data Collection (APDC) and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), which collect data from all public and private hospitals in NSW, Australia. Patients who underwent a TKA or THA for OA between 1 January 2002 and 31 December 2017 were included. The main outcome measures were 90-day incidence rates of hospital readmission for: revision arthroplasty for PJI as recorded in the AOANJRR; conservative definition of PJI, defined by T84.5, the PJI diagnosis code in the APDC; and extended definition of PJI, defined by the presence of either T84.5, or combinations of diagnosis and procedure code groups derived from recursive binary partitioning in the APDC. Results The mean 90-day revision rate for infection was 0.1% (0.1% to 0.2%) for TKA and 0.3% (0.1% to 0.5%) for THA. The mean 90-day PJI rates defined by T84.5 were 1.3% (1.1% to 1.7%) for TKA and 1.1% (0.8% to 1.3%) for THA. The mean 90-day PJI rates using the extended definition were 1.9% (1.5% to 2.2%) and 1.5% (1.3% to 1.7%) following TKA and THA, respectively. Conclusion When reporting the revision arthroplasty for infection, the AOANJRR substantially underestimates the rate of PJI at 90 days. Using combinations of infection codes and PJI-related surgical procedure codes in linked hospital administrative databases could be an alternative way to monitor PJI rates. Cite this article: Bone Joint J 2022;104-B(9):1060–1066.

Background When analyzing the outcomes of joint arthroplasty, an important factor to consider is patient comorbidities. The presence of multiple comorbidities has been associated with longer hospital stays, more postoperative complications, and increased mortality. The American Society of Anesthesiologists (ASA) physical status classification system score is a measure of a patient's overall health and has been shown to be associated with complications and mortality after joint arthroplasty. The Rx-Risk score is another measure for determining the number of different health conditions for which an individual is treated, with a possible score ranging from 0 to 47. Questions/purposes For patients undergoing THA or TKA, we asked: (1) Which metric, the Rx-Risk score or the ASA score, correlates more closely with 30- and 90-day mortality after TKA or THA? (2) Is the Rx-Risk score correlated with the ASA score? Methods This was a retrospective analysis of the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) database linked to two other national databases, the National Death Index (NDI) database and the Pharmaceutical Benefits Scheme (PBS), a dispensing database. Linkage to the NDI provided outcome information on patient death, including the fact of and date of death. Linkage to the PBS was performed to obtain records of all medicines dispensed to patients undergoing a joint replacement procedure. Patients were included if they had undergone either a THA (119,076 patients, 131,336 procedures) or TKA (182,445 patients, 215,712 procedures) with a primary diagnosis of osteoarthritis, performed between 2013 and 2017. We excluded patients with missing ASA information (THA: 3% [3055 of 119,076]; TKA: 2% [4095 of 182,445]). This left 127,761 primary THA procedures performed in 116,021 patients (53% [68,037 of 127,761] were women, mean age 68 ± 11 years) and 210,501 TKA procedures performed in 178,350 patients (56% [117,337 of 210,501] were women, mean age 68 ± 9 years) included in this study. Logistic regression models were used to determine the concordance of the ASA and Rx-Risk scores and 30-day and 90-day postoperative mortality. The Spearman correlation coefficient (r) was used to estimate the correlation between the ASA score and Rx-Risk score. All analyses were performed separately for THAs and TKAs. Results We found both the ASA and Rx-Risk scores had high concordance with 30-day mortality after THA (ASA: c-statistic 0.83 [95% CI 0.79 to 0.86]; Rx-Risk: c-statistic 0.82 [95% CI 0.79 to 0.86]) and TKA (ASA: c-statistic 0.73 [95% CI 0.69 to 0.78]; Rx-Risk: c-statistic 0.74 [95% CI 0.70 to 0.79]). Although both scores were strongly associated with death, their correlation was moderate for patients undergoing THA (r = 0.45) and weak for TKA (r = 0.38). However, the median Rx-Risk score did increase with increasing ASA score. For example, for THAs, the median Rx-Risk score was 1, 3, 5, and 7 for ASA scores 1, 2, 3, and 4, respectively. For TKAs, the median Rx-Risk score was 2, 4, 5, and 7 for ASA scores 1, 2, 3, and 4, respectively. Conclusion The ASA physical status and RxRisk were associated with 30-day and 90-day mortality; however, the scores were only weakly to moderately correlated with each other. This suggests that although both scores capture a similar level of patient illness, each score may be capturing different aspects of health. The Rx-Risk may be used as a complementary measure to the ASA score. Level of evidence Level III, therapeutic study.

BackgroundThe use of health services is likely to vary among veterans with an accepted disability of post-traumatic stress disorder (PTSD), however, the extent of variation is not known. We aimed to determine the extent and type of health services used by veterans with an accepted disability of PTSD.MethodsThe cohort included veterans who served post 1975, were eligible for all Australian Government Department of Veterans’ Affairs funded health services, had PTSD as an accepted disability prior to July 2015 and were alive at the 30 June 2016. Veterans were assigned to groups based on their use of health services using K-means cluster analysis.ResultsThe cohort comprised five clusters involving 2286 veterans. The largest cluster (43%) were a younger, general practitioner (GP) managed cluster who saw their GP quarterly and the psychiatrist twice a year. The second GP cluster (30%) had higher levels of physical comorbidity. The psychiatrist managed cluster (14%) had a mean of 12 psychiatrist visits and one PTSD hospitalisation in the year. The remaining two clusters involved GP and allied healthcare, but no psychologist care. High levels of antidepressant use occurred in all clusters, ranging from 44% up to 69%. The psychiatrist managed cluster had 47% on antipsychotics and 58% on anxiolytics.ConclusionOur study highlights the heterogeneity in health service use. These results identify the significant health utilisation required for up to one-sixth of veterans with PTSD and the significant role of primary care physicians in supporting veterans with PTSD.

Refereed/Peer-reviewed Background and objective: Increasing age, male sex and various chronic conditions have been identified as important risk factors for poor outcomes from COVID-19. The aim of this study was to examine the prevalence of risk factors for poor outcomes due to COVID-19 infection in an older population. Methods: The proportion of the population with one or more risk factors and the prevalence of individual risk factors and multiple risk factors were calculated among Department of Veterans' Affairs (DVA) clients aged >= 70 years. Results: There were 103,422 DVA clients included. Of these, 79% in the community and 82% in residential aged care had at least one risk factor for poor outcomes from COVID-19. Hypertension was most prevalent, followed by chronic heart and airways disease. Over half had >= 2 risk factors, and one in five had >= 3 risk factors across multiple body systems. Discussion: A substantial proportion of older Australians are at risk of poor outcomes from COVID-19 because of their multimorbid risk profile. These patients should be prioritised for proactive monitoring to avoid unintentional harm due to potential omission of care during the pandemic.

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 percent 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 percent 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. Refereed/Peer-reviewed

Background: Poor recognition of medicine‐induced dry mouth can have a number of adverse effects, including difficulties with speech, chewing and swallowing dry foods, gum disease, dental caries and oral candidosis. This study examined the prevalence of use of medicines that cause dry mouth and claims for dental services funded by the Department of Veterans’ Affairs (DVA) in an Australian cohort. Methods: We used the DVA administrative health claims data to identify persons using medicines that can cause dry mouth at 1st of September 2016 and determine their DVA dental claims in the subsequent year. Results were stratified by gender, residence in community or residential aged cared facility, and number of medicines. Results: We identified 50,679 persons using medicines known to cause dry mouth. Of these, 72.6% were taking only one medicine that may cause dry mouth, and 21.6% were taking two. Less than half (46.2%) of all people taking at least one of these medicines had a dental claim in the following year. A smaller proportion of women (35.9%) made claims than men (56.9%), χ2 = 2248.77, p

It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6–30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00–1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88–1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04–1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85–1.12) and 1.24 (95% CI 0.97–1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns Refereed/Peer-reviewed

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.

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.

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.

Medicines acting on the central nervous system can increase the risk of postoperative delirium, but the specific medicines associated with greatest risk remain unclear.We aimed to examine the risk of individual central nervous system-acting medicines used preoperatively on delirium after hip or knee surgery.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.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.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.

Objective: To provide insights into complexities of seeking access to state and federal crossjurisdictional data for linkage with the Australian Childhood Immunisation Register (ACIR). We provide recommendations for improving access and receipt of linked datasets involving Australian Government-administered data. Methods: We describe requirements for linking eleven federal and state data sources to establish a national linked dataset for safety evaluation of vaccines. The required data linkage methodology for integrating cross-jurisdictional data sources is also described. Results: Extensive negotiation was required with 18 different agencies for 21 separate authorisations and 12 ethics approvals. Three variations of the 'best practice' linkage model were implemented. Australian Government approval requests spanned nearly four years from initial request for data, with a further year before ACIR data transfer to the linkage agency. Conclusions: Integration of immunisation registers with other data collections is achievable in Australia but infeasible for routine and rapid identification of vaccine safety concerns. Lengthy authorisation requirements, convoluted disparate application processes and inconsistencies in data supplied all contribute to delayed data availability. Implications for public health: Delayed data access for safety surveillance prevents timely epidemiological reviews. Poor responsiveness to safety concerns may erode public confidence, compromising effectiveness of vaccination programs through reduced participation. Refereed/Peer-reviewed

Objectives Studies have identified increased cancer risk among patients undergoing total hip arthroplasty (THA) compared to the general population. However, evidence of all-cause and site-specific cancer risk associated with different bearing surfaces has varied, with previous studies having short latency periods with respect to use of modern Metal-on-Metal (MoM) bearings. Using the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) linked to Australasian Association of Cancer Registries data, our aim was to evaluate risk of all-cause and site-specific cancer according to bearing surfaces in patients undergoing THA for osteoarthritis and whether risk increased with MoM bearings. Methods Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparing number of observed cancer cases to expected number based on incidence rate in the Australian population. All-cause and site-specific cancer rates were calculated for all conventional stemmed THA (csTHA) and resurfacing THA (rsTHA) procedures performed for osteoarthritis. Cox proportional hazards models were used to compare cancer rates for MoM, ceramic-on-ceramic (CoC) and resurfacing procedures with a comparison group comprising metal-on-polyethylene (MoP) or ceramic-on-polyethylene (CoP) procedures. Results There were 156,516 patients with csTHA procedures and 11,321 with rsTHA procedures for osteoarthritis performed between 1999 and 2012. Incidence of all-cause cancer was significantly higher for csTHA (SIR 1.24, 95% CI 1.22–1.26) and rsTHA (SIR 1.74, 95% CI 1.39–2.04) compared to the Australian population. For csTHA, there was no significant difference in all-site cancer rates for MoM (Hazard Ratio (HR) 1.01, 95%CI 0.96–1.07) or CoC (HR 0.98, 95%CI 0.94–1.02) compared to MoP and CoP bearings. Significantly increased risk of melanoma, non-Hodgkins lymphoma, myeloma, leukaemia, prostate, colon, bladder and kidney cancer was found for csTHA and, prostate cancer, melanoma for rsTHA procedures when compared to the Australian population, although risk was not significantly different across bearing surfaces. Conclusions csTHA and rsTHA procedures were associated with increased cancer incidence compared to the Australian population. However, no excess risk was observed for MoM or CoC procedures compared to other bearing surfaces.

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.The aim of this study was to determine the extent of renal function testing in older people dispensed medicines requiring renal function monitoring.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.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.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.

Objective: To determine the prevalence of medication- related hospitalisations pre-ceded 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 sub-optimal medication- related processes of care. Interventions to improve use of medi-cines for aged care residents in these areas are warranted. Refereed/Peer-reviewed

Background The case-crossover design is suited to medication safety studies but is vulnerable to exposure misclassification. Using the example of tricyclic antidepressants and the risk of hip fracture, we present a data visualisation tool for observing exposure misclassification in case-crossover studies. Methods A case-crossover study was conducted using Australian Government Department of Veterans’ Affairs claims data. Beneficiaries aged over 65 years who were hospitalised for hip fracture between 2009 and 2012 were included. The case window was defined as 1–50 days pre fracture. Control window one and control window two were defined as 101–150 and 151–200 days pre fracture, respectively. Patients were stratified by whether exposure status changed when control window two was specified instead of control window one. To visualise potential misclassification, each subject’s tricyclic antidepressant dispensings were plotted over the 200 days pre fracture. Results The study population comprised 8828 patients with a median age of 88 years. Of these subjects, 348 contributed data to the analyses with either control window. The data visualisation suggested that 14% of subjects were potentially misclassified with control window one while 45% were misclassified with control window two. The odds ratio for the association between tricyclic antidepressants and hip fracture was 1.18 (95% confidence interval = 0.91–1.52) using control window one, whereas risk was significantly increased (odds ratio = 1.43, 95% confidence interval = 1.11–1.83) using control window two. Conclusions Exposure misclassification was less likely to be present with control window one than with an earlier control window, control window two. When specifying different control windows in a case-crossover study, data visualisation can help to assess the extent to which exposure misclassification may contribute to variable results.

The Veterans' Medicines Advice and Therapeutics Education Services (MATES) program is a national data driven, behaviorally informed, health intervention to improve the use of medicines among Australian veterans. The program, which has been operating since 2004, has led the way in the use of government held data assets to generate evidenced-based health information, which, when provided to clinicians alongside educational materials, can make demonstrable improvements in health and promote practice change.

Background This a priori statistical analysis plan describes the analysis for CRISTAL. Methods CRISTAL (cluster-randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study) aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic venous thromboembolism (VTE) following hip arthroplasty (HA) or knee arthroplasty (KA). The study is nested within the Australian Orthopaedic Association National Joint Replacement Registry. The trial was commenced in April 2019 and after an unplanned interim analysis, recruitment was stopped (December 2020), as the stopping rule was met for the primary outcome. The clusters comprised hospitals performing > 250 HA and/or KA procedures per annum, whereby all adults (> 18 years) undergoing HA or KA were recruited. Each hospital was randomised to commence with aspirin, orally, 85–150 mg daily or LMWH (enoxaparin), 40 mg, subcutaneously, daily within 24 h postoperatively, for 35 days after HA and 14 days after KA. Crossover was planned once the registration target was met for the first arm. The primary end point is symptomatic VTE within 90 days. Secondary outcomes include readmission, reoperation, major bleeding and death within 90 days, and reoperation and patient-reported pain, function and health status at 6 months. The main analyses will focus on the primary and secondary outcomes for patients undergoing elective primary total HA and KA for osteoarthritis. The analysis will use an intention-to-treat approach with cluster summary methods to compare treatment arms. As the trial stopped early, analyses will account for incomplete cluster crossover and unequal cluster sizes. Conclusions This paper provides a detailed statistical analysis plan for CRISTAL. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12618001879257. Registered on 19/11/2018.

Refereed/Peer-reviewed Background: The use of cardiac implantable electronic devices (CIED), which includes pacemakers, implantable cardioverter-defibrillators (ICD), cardiac resynchronisation therapy pacemakers (CRT-P) and cardiac resynchronisation therapy defibrillators (CRT-D) has increased over the past 20 years, but there is a lack of real world evidence on the longevity of these devices in the older population which is essential to inform health care delivery and support clinical decisions. Methods and Results: We conducted a retrospective cohort study using data from the Australian Government Department of Veterans’ Affairs database. The cohort consisted of people who had a CIED procedure between 2005 and 2015. The cumulative risk of generator replacement/reoperations was estimated accounting for the competing risk of death. A total of 16,662 patients were included. In pacemaker recipients with an average age of 85 years, the 5-year risk of reoperation ranged from 2.8% in single chamber, 3.6% in dual chamber to 7.6% in CRT-P recipients, while the 5-year risk of dying with the index pacemaker in situ was 63% in single chamber, 46% in dual chamber and 56% in CRT-P recipients. In defibrillator recipients with an average age of 80 years, the 5-year risk of reoperation ranged from 11% in single chamber, 13% in dual chamber to 24% in CRT-D recipients, while the 5-year risk of dying with the index defibrillator in situ was 46% in single chamber, 40% in dual chamber and 41% in CRT-D recipients. Conclusion: In this cohort of older patients the 5-year risk of generator reoperation was low in pacemaker recipients whereas up to one in four CRT-D recipients would have a reoperation within 5 years.

ObjectivesTo 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.DesignA prospective cohort intervention.ParticipantsThe 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 measuresAn 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.ResultsIn the first month after the intervention, the rate of claims increased 6.3-fold (95% CI: 5.2 to 7.6, pConclusionsThe 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.

ObjectiveEducational, 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.DesignWe 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).SettingPrimary care practices providing care to Australian veterans.ParticipantsGeneral practitioners (GPs) targeted by 51 distinct behaviour change interventions, implemented between November 2004 and June 2018.Primary and secondary outcome measuresWe 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.ResultsOn 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.ConclusionsThe finding provides additional evidence encouraging the use of behaviour change techniques, in particular prompt and goal setting, in audit and feedback interventions.

Background: There is increasing interest in the development of statistical models that can be used to estimate risk of adverse patient outcomes after joint arthroplasty. Competing risk approaches have been recommended to estimate risk of longer-term revision, which is often likely to be precluded by the competing risk of death. However, a common approach is to ignore the competing risk by treating death as a censoring event and using standard survival models such as Cox regression. It is well-known that this approach can overestimate the event risk for population-level estimates, but the impact on the estimation of a patient’s individualized risk after joint arthroplasty has not been explored. Questions/purposes: We performed this study to (1) determine whether using a competing risk or noncompeting risk method affects the accuracy of predictive models for joint arthroplasty revision and (2) determine the magnitude of difference that using a competing risks versus noncompeting risks approach will make to predicted risks for individual patients. Methods: The predictive performance of a standard Cox model, with competing risks treated as censoring events, was compared with the performance of two competing risks approaches, the cause-specific Cox model and Fine-Gray model. Models were trained and tested using data pertaining to 531,304 TKAs and 274,618 THAs recorded in the Australian Orthopaedic Association National Joint Replacement Registry between January 1, 2003 and December 31, 2017. The registry is a large database with near-complete capture and follow-up of all hip and knee joint arthroplasty in Australia from 2003 onwards, making it an ideal setting for this study. The performance of the three modeling approaches was compared in two different prediction settings: prediction of the 10-year risk of all-cause revision after TKA and prediction of revision for periprosthetic fracture after THA. The calibration and discrimination of each approach were compared using the concordance index, integrated Brier scores, and calibration plots. Calibration of 10-year risk estimates was further assessed within subgroups of age by comparing the observed and predicted proportion of events. Estimated 10-year risks from each model were also compared in three hypothetical patients with different risk profiles to determine whether differences in population-level performance metrics would translate into a meaningful difference for individual patient predictions. Results: The standard Cox and two competing risks models showed near-identical ability to distinguish between high-risk and low-risk patients (c-index 0.64 [95% CI, 0.64 to 0.64] for all three modeling approaches for TKAs and 0.66 [95% CI 0.66 to 0.66] for THA). All models performed similarly in patients younger than 75 years, but for patients aged 75 years and older, the standard Cox model overestimated the risk of revision more than the cause-specific Cox and Fine-Gray model did. These results were echoed when predictions were made for hypothetical individual patients. For patients with a low competing risk of mortality, the 10-year predicted risks from the standard Cox, cause-specific Cox, and Fine-Gray models were similar for TKAs and THAs. However, a larger difference was observed for hypothetical 89-year-old patients with increased mortality risk. In TKAs, the revision risk for an 89-year-old patient was so low that this difference was negligible (0.83% from the cause-specific Cox model versus 1.1% from the standard Cox model). However, for THAs, where older age is a risk factor for both death and revision for periprosthetic fracture, a larger difference was observed in the 10-year predicted risks for a hypothetical 89-year-old patient (3.4% from the cause-specific Cox model versus 5.2% from the standard Cox model). Conclusion: When developing models to predict longer-term revision of joint arthroplasty, failing to use a competing risks modeling approach will result in overestimating the revision risk for patients with a high risk of mortality during the surveillance period. However, even in an extreme instance, where both the frequency of the event of interest and the competing risk of death are high, the largest absolute difference in predicted 10-year risk for an individual patient was just 1.8%, which may not be of consequence to an individual. Despite these findings, when developing or using risk prediction models, researchers and clinicians should be aware of how competing risks were handled in the modeling process, particularly if the model is intended for use populations where the mortality risk is high. Level of Evidence: Level III, therapeutic study. Refereed/Peer-reviewed

Objective To determine whether differences in combination DTaP vaccine types at 2, 4 and 6 months of age were associated with mortality (all-cause or non-specific), within 30 days of vaccination. Design Observational nationwide cohort study. Setting Linked population data from the Australian Childhood Immunisation Register and National Death Index. Participants Australian infants administered a combination trivalent, quadrivalent or hexavalent DTaP vaccine (DTaP types) between January 1999 and December 2010 at 2, 4 and 6 months as part of the primary vaccination series. The study population included 2.9, 2.6, & 2.3 million children in the 2, 4 and 6 month vaccine cohorts, respectively. Main outcome measures Infants were evaluated for the primary outcome of all-cause mortality within 30 days. A secondary outcome was non-specific mortality (unknown cause of death) within 30 days of vaccination. Non-specific mortality was defined as underlying or other cause of death codes, R95 ‘Sudden infant death syndrome’, R96 ‘Other sudden death, cause unknown’, R98 ‘Unattended death’, R99 ‘Other ill-defined and unspecified cause of mortality’ or where no cause of death was recorded. Results The rate of 30 day all-cause mortality was low and declined from 127.4 to 59.3 deaths per 100,000 person-years between 2 and 6 month cohorts. When compared with trivalent DTaP vaccines, no elevated risk in all-cause or non-specific mortality was seen with any quadrivalent or hexavalent DTaP vaccines, for any cohort. Conclusion Use of routine DTaP combination vaccines with differing disease antigens administered during the first six months of life is not associated with infant mortality.

Background Four-component meningococcal B (4CMenB) vaccine is licensed in many countries but has had limited use in adolescents despite this age group being at increased risk of meningococcal disease. Objectives To assess the safety profile of two doses of 4CMenB in adolescents. Methods Cluster randomised controlled trial of senior school students in South Australia (SA) with participating schools randomised to intervention (4CMenB) or control. Vaccine safety was monitored using the South Australian Vaccine Safety Surveillance System (SAVSS), a spontaneous reporting system for adverse events following immunisation (AEFI) with enhanced follow-up of AEFI. Results 58,637 doses of 4CMenB vaccine were administered to 30,522 students (median age 16 years) during 2017–2018. Of 18,348 and 12,174 students vaccinated in 2017 and 2018, 97.3% and 84.3%, respectively, received both scheduled doses (N = 28,115). 193 AEFI in 187 students were reported with a reporting rate of 0.32% (95%CI: 0.28–0.39%). Seventy individuals sought medical review, including nine serious adverse events. 98% (166/169) of those who were contactable for AEFI follow-up (87.6% 169/193) reported resolution of the event. Most common AEFI were injection site reaction (126/193), headache (99/193) and nausea (61/193). AEFI were more frequently reported in females (aOR = 1.409 (95%CI: 1.002, 1.980)), schools with high level of educational advantage (adjusted Odds Ratio (aOR) = 1.515 (95%CI: 1.005, 2.284)), following first dose (aOR = 1.619 (95%CI: 1.168, 2.244)), and in 2017 (aOR = 1.437 (95%CI: 1.001, 2.064)). Reported AEFI declined with increasing age (aOR = 0.771 (95%CI: 0.673, 0.883)). Conclusion In this largest post-licensure use of 4CMenB in adolescents, the low AEFI reporting rate provides real-world evidence of 4CMenB safety in this age group. (ClinicalTrials.gov number: NCT03089086).

Summary Background The use of medications to treat attention deficit hyperactivity disorder (ADHD) has increased, but the prevalence of ADHD medication use across different world regions is not known. Our objective was to determine regional and national prevalences of ADHD medication use in children and adults, with a specific focus on time trends in ADHD medication prevalence. Methods We did a retrospective, observational study using population-based databases from 13 countries and one Special Administrative Region (SAR): four in Asia and Australia, two in North America, five in northern Europe, and three in western Europe. We used a common protocol approach to define study populations and parameters similarly across countries and the SAR. Study populations consisted of all individuals aged 3 years or older between Jan 1, 2001, and Dec 31, 2015 (dependent on data availability). We estimated annual prevalence of ADHD medication use with 95% CI during the study period, by country and region and stratified by age and sex. We reported annual absolute and relative percentage changes to describe time trends. Findings 154·5 million individuals were included in the study. ADHD medication use prevalence in 2010 (in children aged 3–18 years) varied between 0·27% and 6·69% in the countries and SAR assessed (0·95% in Asia and Australia, 4·48% in North America, 1·95% in northern Europe, and 0·70% in western Europe). The prevalence of ADHD medication use among children increased over time in all countries and regions, and the absolute increase per year ranged from 0·02% to 0·26%. Among adults aged 19 years or older, the prevalence of any ADHD medication use in 2010 varied between 0·003% and 1·48% (0·05% in Asia and Australia, 1·42% in North America, 0·47% in northern Europe, and 0·03% in western Europe). The absolute increase in ADHD medication use prevalence per year ranged from 0·0006% to 0·12%. Methylphenidate was the most commonly used ADHD medication in most countries. Interpretation Using a common protocol and data from 13 countries and one SAR, these results show increases over time but large variations in ADHD medication use in multiple regions. The recommendations of evidence-based guidelines need to be followed consistently in clinical practice. Further research is warranted to describe the safety and effectiveness of ADHD medication in the short and long term, and to inform evidence-based guidelines, particularly in adults. Funding None

Background: Frailty and medicine-related problems are common among the elderly and have been associated with an increased risk of adverse outcomes. However, there has been limited research on the association between frailty and medicines use. Aim: To determine the distribution of frailty among older people who used medicines and to examine the difference in frailty scores over time with continuation or discontinuation of specific medicines. Methods: The study population was from the Australian Longitudinal Study of Ageing (ALSA). The data used in the analysis were collected in 1992 (wave 1) and in 1995 (wave 3). Frailty scores were assessed at both waves using a modified version of the Frailty Index. Non-parametric tests were used to examine the difference in the distribution of frailty scores in relation to medicines used at baseline. Medicine use was categorised into continued or stopped by comparing use at wave 3 to use at baseline. A t-test was used to compare the mean changes in frailty scores between the two groups, with a p-value of

Based on data from the Longitudinal Study of Australian Children linked with pharmacy dispensing data from the Australian Government’s Pharmaceutical Benefits Scheme, we calculated the 1-year prevalence of psychotropic medicine supply in children and adolescents with Autism Spectrum Disorder (ASD) as reported by parents in 2014. The majority of children and adolescents with ASD in Australia were not treated with psychotropic medicine. One-third had claims for at least one psychotropic medication, most commonly medications for attention-deficit/hyperactivity disorder (ADHD), and antidepressants. Antipsychotics were supplied to less than one in twenty children and approximately one in ten adolescents. In line with findings from North America, psychotropic medicine was more often supplied to children and adolescents with ASD and comorbid ADHD. Refereed/Peer-reviewed

Aim: To compare persistence in people who initiate the combination of amlodipine and statin as a fixed-dose combination (FDC) or separate pill combination (SePC), and assess the impact of prior medicine exposure on this outcome. Method: Prescription dispensing data from a national administrative dataset was used to identify patients initiating FDCs or SePCs of amlodipine and statin between April and September 2013. Each cohort was stratified according to dispensing of calcium channel blockers (CCBs) or statins in the prior 12 months. Time to cessation of combination therapy (persistence) was analyzed over 12 months using Kaplan Meyer survival analysis and Cox proportional hazards (PH) models. Patient factors associated with length of treatment were identified using Cox PH modeling. Results: Of 26,000 people who initiated combination amlodipine and statin, the majority initiated SePCs (77%). The unadjusted cessation rates at 12 months were SePC 40% and FDC 44%. Following adjustment for patient factors, the risk of ceasing combination therapy was higher in those taking the SePC versus FDC, hazard ratio (95% CI): 1.15 (1.11, 1.21). Patients naïve to both therapies had double the cessation rate compared to those who had at least one prior dispensing of a statin. Factors positively associated with persistence were prior use of other antihypertensive drugs and reaching the medicine subsidy safety-net: factors that were more common in users of SePC amlodipine and statin. Conclusion: In this study we found a lower risk (15%) of ceasing combination therapy when people initiate amlodipine and statin in the form of a FDC. While this outcome supports findings in other countries that FDCs improve persistence with combination therapy, prior experience with component or similar medicines has a larger impact on persistence regardless of formulation initiated.

Background Few studies have assessed the risk of hip fracture following concurrent use of psychoactive medicines, and none has investigated combinations with selective serotonin reuptake inhibitors. Objectives To assess the risk of hip fracture in older people as a result of concurrent use of selective serotonin reuptake inhibitors and other psychoactive medicines. Methods A matched case–control design was employed. Cases were Australian Government Department of Veterans’ Affairs beneficiaries aged over 65 years who experienced a hip fracture between 2009 and 2012. Each case was matched with up to four randomly selected controls of the same age (±2 years) and sex. Medicine-hip fracture associations were estimated via conditional logistic regression. The relative excess risk due to interaction (RERI) was calculated to determine whether combined effects differed from the sum of individual effects. Results There were 8828 cases and 35,310 controls. The median age of subjects was 88 years and 63% were women. The risk of hip fracture was elevated for all medicines assessed individually, most notably selective serotonin reuptake inhibitors (initiation: odds ratio [OR] = 2.7, 95% confidence interval [CI] 2.1, 3.6) and opioids (initiation: OR = 2.3, 95% CI 1.9, 2.9). Combinations associated with an increased odds of hip fracture included addition of benzodiazepines to selective serotonin reuptake inhibitor therapy (OR = 3.0, 95% CI 1.9, 4.8; RERI = 0.9, 95% CI −0.5, 2.3), concurrent use of both opioids and selective serotonin reuptake inhibitors (OR = 2.2, 95% CI 1.9, 2.6; RERI = 0.1, 95% CI −0.3, 0.5), addition of opioids to selective serotonin reuptake inhibitor therapy (OR = 3.2, 95% CI 1.8, 5.5; RERI = −0.1, 95% CI −2.0, 1.7), and initiation of both benzodiazepines and selective serotonin reuptake inhibitors (OR = 4.7, 95% CI 1.7, 13; RERI = 1.3, 95% CI −3.8, 6.3). The RERI results suggested that the effect of each of these medicine combinations equalled the sum of the effects of individual medicine use. Conclusions In older people, the concurrent use of selective serotonin reuptake inhibitors and other psychoactive medicines increased the risk of hip fracture as much as the sum of the risks owing to individual medicine use. Our results highlight the need for prescribers to consider the sedative burden of medicines in each older patient as well as the potential for an additive risk of hip fracture when initiating additional psychoactive therapy.

Objectives: To examine the risk of dementia associated with posttraumatic stress disorder (PTSD) and the contribution of antipsychotic use to this risk. Design: Retrospective cohort study Setting: Australia. Administrative claims data from the Australian Government Department of Veterans' Affairs were used. Participants: Male Vietnam veterans aged 55 to 65 at baseline (2001-02) with no preexisting dementia diagnosis (N = 15,612). Measurements: The association between PTSD and dementia was assessed over 12 years of follow-up. Dementia was identified as a hospital diagnosis, dementia record in service disability data, or dispensing of medicines for dementia. Cox-proportional hazards models were used, with age as the time-scale. Results were stratified according to baseline antipsychotic use. Results: No greater risk of dementia was observed with PTSD. In veterans who received antipsychotics, dementia risk was significantly higher than in those who did not (hazard ratio (HR) = 2.1, 95% confidence interval (CI) = 1.4-3.3). Dementia risk was significantly greater in veterans hospitalized for PTSD who received antipsychotics (HR = 2.2, 95% CI = 1.1-4.6) and veterans without PTSD who received antipsychotics (HR = 4.3, 95% CI = 2.1-8.6) than in those without PTSD with no antipsychotic use. Conclusion: Antipsychotic use may be a contributor to dementia risk. These findings should be interpreted with caution because the study design was observational. Further research using prospective study designs in settings where diagnostic data, cognitive function, and disease severity are available are required. Refereed/Peer-reviewed

Objective: To identify factors that contribute to older Australians admitted to hospital with diabetes being re-hospitalised within 30 days of discharge. Design, setting and participants: A retrospective cohort study of Department of Veterans’ Affairs administrative data for all patients hospitalised for diabetes and discharged alive during the period 1 January – 31 December 2012. Main outcome measures: Causes of re-hospitalisation and prevalence of clinical factors associated with re-hospitalisation within 30 days of discharge. Methods: Multivariate logistic regression analysis (backward stepwise) was used to identify characteristics predictive of 30-day re-hospitalisation. Results: 848 people were hospitalised for diabetes; their median age was 87 years (interquartile range, 77–89 years) and 60% were men. 209 patients (24.6%) were re-hospitalised within 30 days of discharge, of whom 77.5% were re-admitted within 14 days of discharge. 51 re-hospitalisations (24%) were for diabetes-related conditions; 41% of those re-admitted within 14 days had not seen their general practitioner between discharge and re-admission. Factors predictive of rehospitalisation included comorbid heart failure (adjusted odds ratio [aOR], 1.49; 95% confidence interval [CI], 1.03–2.17; P = 0.036), numbers of prescribers in previous year (aOR [for each additional prescriber], 1.06; 95% CI, 1.01–1.08; P = 0.031), and two or more hospitalisations in the 6 months before the index admission (aOR, 1.79; 95% CI 1.15–2.78; P = 0.009). Conclusion: Older people hospitalised for diabetes who have comorbid heart failure, multiple recent hospitalisations, and multiple prescribers involved in their care are at greatest risk of being re-admitted to hospital within 30 days. Targeted follow-up during the initial 14 days after discharge may facilitate appropriate interventions that avert re-admission of these at-risk patients. Refereed/Peer-reviewed

Introduction: Medicine safety signal detection methods employed by the medicine regulator in Australia (Therapeutic Goods Administration [TGA], Department of Health) rely predominantly on analysis of spontaneous adverse event (AE) reports, sponsor notifications or information shared by international agencies. The limitations of these methods and the availability of large administrative health data sets has given rise to greater interest in the use of administrative health data to support pharmacovigilance (PV). Objective: We explored whether prescription sequence symmetry analysis (PSSA) of Pharmaceutical Benefits Scheme (PBS) data can enhance signal detection by the TGA, using the AE, heart failure (HF) as a case study. Methods: We applied the PSSA method to all single-ingredient medicines dispensed under the PBS between 2012 and 2016, using furosemide initiation as a proxy for new-onset HF. A signal was considered present if the lower limit of the 95% confidence interval for the adjusted sequence ratio was > 1. We excluded medicines known to cause HF, indicated for HF treatment or indicated for diseases that may contribute to HF. Results: Of the 654 tested medicines, 26 potential new HF signals were detected by PSSA. Five signals had additional support for the possible association provided by biological plausibility, consistency and disproportionate reporting of cases of HF to the TGA and the World Health Organization; and clinical impact. Conclusion: PSSA was able to identify potential signals for further evaluation. With the increasing availability of different administrative health data sources, the strengths and weaknesses of methods used to analyse these data for the purpose of regulatory PV should be evaluated. Refereed/Peer-reviewed

ObjectiveTo measure the paediatric user and prescription prevalence in inpatient and ambulatory settings in South Korea, Hong Kong, Taiwan, Japan and Australia by age and gender. A further objective was to list the most commonly used drugs per drug class, per country.Design and settingHospital inpatient and insurance paediatric healthcare data from the following databases were used to conduct this descriptive drug utilisation study: (i) the South Korean Ajou University School of Medicine database; (ii) the Hong Kong Clinical Data Analysis and Reporting System; (iii) the Japan Medical Data Center; (iv) Taiwan’s National Health Insurance Research Database and (v) the Australian Pharmaceutical Benefits Scheme. Country-specific data were transformed into the Observational Medical Outcomes Partnership Common Data Model.PatientsChildren (≤18 years) with at least 1 day of observation in any of the respective databases from January 2009 until December 2013 were included.Main outcome measuresFor each drug class, we assessed the per-protocol overall user and prescription prevalence rates (per 1000 persons) per country and setting.ResultsOur study population comprised 1 574 524 children (52.9% male). The highest proportion of dispensings was recorded in the youngest age category (ConclusionsCountry-specific paediatric drug utilisation patterns were described, ranked and compared between four East Asian countries and Australia. The widespread use of mucolytics in East Asia warrants further investigation.

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. Refereed/Peer-reviewed

IntroductionVenous thromboembolism (VTE) is a serious complication following hip arthroplasty (HA) and knee arthroplasty (KA). This study aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic VTE following HA and KA.Methods and analysisThis is a cluster randomised, crossover, non-inferiority, trial nested within the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). The clusters will consist of Australian hospitals performing at least 250 HA and/or KA procedures per annum. All adult patients undergoing HA or KA will be included. The intervention will be aspirin, orally, 85–150 mg daily. The comparator will be LMWH (enoxaparin) 40 mg, subcutaneously, daily. Both drugs will commence within 24 hours postoperatively and continue for 35 days after HA and 14 days after KA. Each hospital will be randomised to commence with aspirin or LMWH and then crossover to the alternative treatment after meeting the recruitment target. Data will be collected through the AOANJRR via patient-reported surveys. The primary outcome is symptomatic VTE within 90 days post surgery, verified by AOANJRR staff. The primary analysis will include only patients undergoing elective primary total hip arthroplasty and total knee arthroplasty for osteoarthritis. Secondary outcomes will include symptomatic VTE for all HA and KA (including partial and revision) within 90 days, readmission, reoperation, major bleeding and death within 90 days and reoperation, death and patient-reported pain, function and health status at 6 months. If aspirin is found to be inferior, a cost-effectiveness analysis will be conducted. The study will aim to recruit 15 562 patients from 31 hospitals.Ethics and disseminationEthics approval has been granted. Trial results will be submitted for publication. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001879257, pre-results) and is endorsed by the Australia and New Zealand Musculoskeletal Clinical Trials Network.

ObjectiveTo determine time to opioid cessation post discharge from hospital in persons who had been admitted to hospital for a surgical procedure and were previously naïve to opioids.Design, setting and participantsRetrospective cohort study using administrative health claims database from the Australian Government Department of Veterans’ Affairs (DVA). DVA gold card holders aged between 18 and 100 years who were admitted to hospital for a surgical admission between 1 January 2014 and 30 December 2015 and naïve to opioid therapy prior to admission were included in the study. Gold card holders are eligible for all health services that DVA funds.Main outcome measuresThe outcome of interest was time to cessation of opioids, with follow-up occurring over 12 months. Cessation was defined as a period without an opioid prescription that was equivalent to three times the estimated supply duration. The proportion who became chronic opioid users was defined as those who continued taking opioids for greater than 90 days post discharge. Cumulative incidence function with death as a competing event was used to determine time to cessation of opioids post discharge.ResultsIn 2014–2015, 24 854 persons were admitted for a surgical admission. In total 3907 (15.7%) were discharged on opioids. In total 3.9% of those discharged on opioids became chronic users of opioids. The opioid that the patients were most frequently discharged with was oxycodone; oxycodone alone accounted for 43%, while oxycodone with naloxone accounted for 8%.ConclusionsOpioid initiation post-surgical hospital admission leads to chronic use of opioids in a small percentage of the population. However, given the frequency at which surgical procedures occur, this means that a large number of people in the population may be affected. Post-discharge assessment and follow-up of at-risk patients is important, particularly where psychosocial elements such as anxiety and catastrophising are identified.

Background: Most studies assessing the effect of central nervous system (CNS)-acting medicines on cognitive disturbances have focused on the use of individual medicines. The impact on cognitive function when another CNS-acting medicine is added to a patient's treatment regimen is not well known. Objective: To determine risk of hospitalization for confusion, delirium, or dementia in older people associated with increasing numbers of CNS-acting medicines taken concurrently, as well as the number of standard doses taken each day (measured as defined daily doses). Design: Retrospective cohort study, from July 2011 to June 2012, using health claims data. Setting: Australian veteran population. Participants: A total of 74,321 community-dwelling individuals aged 65 years and over, who were dispensed at least 1 CNS-acting medicine in the year before study entry. Patients with prior hospitalization for confusion or delirium, and those with dementia or receiving palliative care, were excluded. Main outcome measure: Hospitalization for confusion, delirium, or dementia. Results: Over the 1-year study period, 401 participants were hospitalized with confusion, delirium, or dementia. Adjusted analyses showed the risk of hospitalization was 2.4 times greater with the use of 2 CNS-acting medicines compared with no use [incident rate ratio (IRR) 2.39, 95% confidence interval (CI) 1.79-3.19, P < .001], and more than 19 times greater when 5 or more CNS-acting medicines were taken concurrently (IRR 19.35, 95% CI 11.10-33.72, P < .001). Similarly, the risk of hospitalization was significantly increased among patients taking between 1.0 and 1.9 standard doses per day (IRR 2.64, 95% CI 1.99-3.50, P < .001) and between 2.0 and 2.9 standard doses per day (IRR 3.43, 95% CI 2.07-5.69, P < .001) compared with no use. Conclusions: Use of multiple CNS-acting medicines or higher doses is associated with an increased risk of hospitalization for confusion, delirium, or dementia. Health care professionals need to be alert to the contribution of CNS-acting medicines among patients presenting with confusion or delirium and consider strategies to reduce treatment burden where possible. Refereed/Peer-reviewed

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

Background: Internationally, antipsychotics are frequently initiated during hospital admission for older patients and use often continues post-discharge without indication. We located no Australian studies on this topic. Objective to identify the hospital admissions (excluding psychosis) associated with antipsychotic initiation and continuation in older Australians. Setting Australian Government Department of Veterans’ Affairs. Method Retrospective analysis of administrative claims data for people admitted to hospital from 1 January 2014 to 31 December 2014, aged ≥ 65 years, who were antipsychotic naïve. Main outcome measure number of admissions associated with antipsychotic initiation, and the major diagnosis groups for these admissions.Where antipsychotics were initiated, we determined the time to cessation of antipsychotics after discharge. Results There were142,009 hospital admissions for 66,415 people with a median age of 86 years. 921 (0.65%) admissions were associated with antipsychotic initiation, most commonly where the primary diagnoses were for mental and behavioural disorders excluding psychosis (17.8%) and injuries (16%). Fourteen percent of antipsychotic initiations were for primary diagnoses of deliriumor dementia. When secondary diagnoses were considered, 55% of antipsychotic initiations were associated with delirium,dementia or both. The median duration of use among people who used antipsychotics was 132 days, and 40% continued use until death or one year follow-up. Conclusion Initiation of antipsychotics during hospital admissions was not frequent in this Australian population. Amongst those who did initiate antipsychotics, for almost half no diagnosis corresponding withan approved indication for use was recorded and long-term use of up to one year was common. Refereed/Peer-reviewed

Objectives: To describe how post-market utilisation analysis in Australia informs cost-effectiveness assessment and pricing decisions, using aflibercept and ranibizumab as case studies. Methods: Pharmaceutical claims were used to identify initiators of aflibercept and ranibizumab in the year after aflibercept-listing (December 2012), and ranibizumab initiators in the year before aflibercept listing. The dispensing rates for each cohort were calculated, and their demographic and clinical characteristics compared using Kruskal-Wallis tests. Results: Aflibercept and ranibizumab each accounted for half the age-related macular degeneration market following ranibizumab listing. Aflibercept initiators had similar dispensing rates to ranibizumab initiators in the pre- and post-aflibercept era (~ three scripts during the first 90 days, and eight to nine scripts during the following 12 months). All cohorts were similar in terms of their age, sex, residential aged-care status and geographic remoteness, and no differences were observed in their overall co-morbidity scores and history of thromboembolic events. Conclusions: Contrary to clinical trial protocols, post-market utilisation research for ranibizumab and aflibercept demonstrates equivalent use in practice in terms of dose frequency, and the demographic and clinical characteristics of initiators. This supports Australia's decision to pay the same price for each rather than giving a premium to aflibercept. Many other countries are likely overpaying for aflibercept if their utilization patterns are similar to Australia's, and could benefit from incorporating routine utilisation assessment. Refereed/Peer-reviewed

ObjectivesThe aim of this study was to compare effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin in the Australian Veteran population.DesignSequential cohort study using inverse probability of treatment weighting (IPTW) and propensity score matching. Initiators of high-strength (apixaban 5 mg, dabigatran 150 mg, rivaroxaban 20 mg) and low-strength DOACS (apixaban 2.5 mg, dabigatran 110 mg, rivaroxaban 15 mg) were compared with warfarin initiators.SettingAustralian Government Department of Veterans’ Affairs claims database.Participants4836 patients who initiated oral anticoagulants (45.8%, 26.0% and 28.2% on low-strength, high-strength DOACs and warfarin, respectively) between August 2013 and March 2015. Mean age was 85, 75 and 83 years for low-strength, high-strength DOACs and warfarin initiators, respectively.Main outcome measuresOne-year risk of hospitalisation for ischaemic stroke, any bleeding event or haemorrhagic stroke. Secondary outcomes were 1-year risk of hospitalisation for myocardial infarction and death.ResultsUsing the IPTW method, no difference in risk of ischaemic stroke or bleeding was found with low-strength DOACs compared with warfarin. As a class, no increased risk of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban (HR 2.25, 95% CI 1.23 to 4.13). For high-strength DOACs, no difference was found for ischaemic stroke compared with warfarin, however, there was a significant reduction in risk of bleeding events (HR 0.63, 95% CI 0.44 to 0.89) and death (HR 0.40, 95% CI 0.28 to 0.58). Propensity score matching showed no difference in risk of ischaemic stroke or bleeding.ConclusionWe found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.

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 sedativeuse 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 June2012, 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 Refereed/Peer-reviewed

Background Prescription sequence symmetry analysis (PSSA) is a signal detection method for adverse drug events. Its capacity to consistently detect adverse drug events across different settings has not been tested. We aimed to determine the consistency of PSSA results for detecting positive and negative control adverse drug events across different settings. Methods Using a distributed network model, we analyzed prescription dispensing data using PSSA in Australia, Hong Kong, Japan, Korea, and Taiwan. Positive control was amiodarone and thyroxine, as a marker of amiodarone-induced hypothyroidism, a known adverse event with a clear temporal relationship to amiodarone initiation. Negative controls were amiodarone and allopurinol, as a marker of amiodarone-induced gout and thyroxine and allopurinol, as a marker of thyroxine-induced gout. Gout is not recorded as an adverse event in product information for either medicine. Adjusted sequence ratios (ASR) were calculated for each country. Pooled estimates were obtained by using the generic inverse variance method. Results A positive association was identified between amiodarone and thyroxine in all settings with a pooled ASR 2.63 (95% confidence interval (CI) 1.47–4.72). Temporal analysis showed the effect occurred within the first few weeks of treatment. No significant associations were found for the negative controls in any setting; pooled ASR were 0.76 (95%CI 0.62–0.93) and 0.98 (95%CI 0.85–1.12) for amiodaroneallopurinol and thyroxine-allopurinol, respectively. Conclusion Despite different health settings, different populations, and different patterns of medicine utilization, PSSA gave consistent estimates across countries for a well-known positive association and two negative control adverse events. © 2015 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. key words—prescription symmetry analysis; pharmacovigilance; amiodarone; hyperthyroidism; pharmacoepidemiology

Background: Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) are common conditions. The use of mesh in the surgical treatment of these conditions in Australia is unclear. Aim: To examine the use of mesh in POP and SUI procedures in an Australian national cohort of older women. Methods: We conducted a population‐based cohort study using data from the Australian Government Department of Veterans' Affairs (DVA) database. The cohort consisted of older women who had POP and SUI procedures between 1 July, 2005 and 31 December, 2016. Women who received mesh were identified by matching device billing codes with the Australian Government's Prosthesis List. Results: In total, 3129 women experienced 3472 hospitalisations for POP and SUI procedures, with 74% of the women aged 75 years and older. There were 2276 (66%) hospitalisations with single POP repairs, 608 (18%) with single SUI procedures and 588 (17%) with concomitant POP and SUI procedures. Mesh was used in 23% of single procedures for POP, in 89% of single procedures for SUI and in 90% of concomitant POP and SUI procedures. The use of mesh in POP procedures decreased from a peak of 33% in 2008 down to 8% by 2016, whereas the use of mesh in SUI procedures increased from 77% in 2006 to 91% by 2016. Conclusion: Mesh was commonly used in SUI procedures, whereas use of mesh in POP repair was less common and the use decreased rapidly after 2011, when warnings about use of mesh in POP were first issued. Refereed/Peer-reviewed

Purpose: The safety of nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in Asia-Pacific countries has had limited study. We assessed the risk of hospitalization for gastrointestinal events with loxoprofen and mefenamic acid compared with other NSAIDs in Asia-Pacific populations. Methods: We conducted a cohort study using a distributed network with a common data model in Australia, Hong Kong, Japan, Korea, and Taiwan. We included patients who initiated diclofenac, loxoprofen, mefenamic acid, or celecoxib and followed them until their first gastrointestinal hospitalization, switch or discontinuation of medication, disenrollment, or end of database coverage. We used Cox proportional hazards models to assess hospitalization risk. Results: We identified 9879 patients in Japan, 70 492 in Taiwan, 263 741 in Korea, and 246 in Hong Kong who initiated an NSAID, and 44 013 patients in Australia, a predominantly Caucasian population. The incidence of gastrointestinal hospitalization was 25.6 per 1000 person-years in Japan, 32.8 in Taiwan, 11.5 in Korea, 484.5 in Hong Kong, and 35.6 in Australia. Compared with diclofenac, the risk of gastrointestinal events with loxoprofen was significantly lower in Korea (hazards ratio, 0.37; 95% CI, 0.25-0.54) but not in Japan (1.65; 95% CI, 0.47-5.78). The risk of gastrointestinal events with mefenamic acid was significantly lower in Taiwan (0.45; 95% CI, 0.26-0.78) and Korea (0.11; 95% CI, 0.05-0.27) but not Hong Kong (2.16; 95% CI, 0.28-16.87), compared with diclofenac. Conclusions: Compared with diclofenac, loxoprofen was associated with a lower risk of gastrointestinal hospitalizations in Korea and mefenamic acid with a lower risk in Taiwan and Korea Refereed/Peer-reviewed

Background: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.

National interventions to promote HMRs, comprising patient‐specific prescriber feedback and tailored educational materials for patients and clinicians, were conducted in 2004, 2006 and 2011 through the Veterans’ Medicines Advice and Therapeutics Education Services (Veterans’ MATES) program. Primary care patients taking multiple medicines were targeted in each intervention, while primary care patients taking multiple medicines who did not receive the intervention served as comparisons. Monthly HMR rates among targeted patients and a comparison group in the 9 months post‐intervention were determined using health claims data from the Australian Government Department of Veterans’ Affairs and compared using log binomial regression models. Overall trends in the rate of HMRs between November 2001 and December 2016 were also determined. Refereed/Peer-reviewed

Objectives: To evaluate the prevalence and change in analgesic medications use prior to joint replacement in older patients between 2001 and 2012. Methods: A population based epidemiological study was conducted. Opioids, non-steroidal anti-inflammatories (NSAIDs), paracetamol, corticosteroid injections, medications for neuropathic pain, hypnotics, and muscle relaxants supplied 1 year prior to total knee replacement (TKR, n = 15,517) and hip replacement (THR, n = 10,018) were assessed. Patient characteristics and surgical indication adjusted prevalence ratios (PRs) and 95% confidence intervals (CI) are provided. Results: From 2001 to 2012, in the TKR cohort (median age 78.9) the prevalence of opioid use prior to surgery increased from 37% to 49% (PR = 1.01, 95% CI 1.00-1.01, P = 0.01), while in the THR cohort (median age 81.1) it increased from 44% to 54% (PR = 1.01, 95% CI 1.01-1.02, P < 0.001). Paracetamol use increased from 52% to 61% (PR = 1.0, 95% CI 1.0-1.0, P = 0.913) in the TKR cohort and from 55% to 67% (PR = 1.01, 95% CI 1.00-1.01, P = 0.005) in the THR cohort. Neuropathic pain medication use increased from 5% to 11% in the TKR cohort (PR = 1.04, 95% CI 1.02-1.06, P < 0.0001) and from 6% to 12% in the THR cohort (PR = 1.06, 95% CI 1.04-1.09, P < 0.0001). NSAID use decreased from 76% to 50% in the TKR cohort (PR = 0.96, 95% CI 0.95-0.96, P < 0.0001), and from 81% to 47% in THR cohort (PR = 0.95, 95% CI 0.94-0.95, P < 0.0001). Corticosteroid injections prevalence also decreased (TKR: 21-18%, PR = 0.97, 95% CI 0.96-0.97, P < 0.001, THR: 18-17%, PR = 0.97, 95% CI 0.96-0.98, P < 0.001). Conclusion: Pain medication utilization prior to joint replacement surgery changed significantly in this national older cohort of patients during the 2000s. Refereed/Peer-reviewed

Introduction: A large number of older people receive pacemakers each year but broad population-based studies that describe complications following pacemaker implantation in this population are lacking. Methods: We conducted a retrospective cohort study using data from the Australian Government Department of Veterans' Affairs database. The cohort consisted of patients who received a pacemaker from 2005 to 2014. The outcomes were subsequent rehospitalizations for infections, procedure-related complications, thromboembolism, cardiovascular events (heart failure, myocardial infarction, and atrial fibrillation), and reoperation of pacemaker, and mortality. Results: There were 10 883 pacemakers recipients, the median age was 86 years (interquartile range 83-89), 61% were males, and 74% received a dual-chamber pacemaker. Within 90 days postdischarge, rehospitalizations were occasioned by pacemaker infection in 0.5%, device-related complications in 1.5%, cerebral infarction in 0.7%, and heart failure in 6% of single-chamber pacemaker recipients. In dual-chamber pacemaker recipients rehospitalizations were occasioned by pacemaker infection in 0.4%, septicemia in 0.4%, device-related complications in 1.2%, cerebral infarction in 0.3%, and heart failure in 3%. Rehospitalizations for pacemaker adjustment occurred in 1.5% of patients. The 90-day postdischarge mortality was 5% and 3% in patients with single- and dual-chamber pacemaker, respectively. Conclusion: Rehospitalizations for infection, procedure-related complications, or thromboembolism occurred in 1% to 2% of patients within 90 days postdischarge, while 10% of single chamber and 7% of dual-chamber recipients experienced a rehospitalization for a cardiovascular event. Refereed/Peer-reviewed