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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.

Background: Antidepressants are associated with adverse effects such as sedation and hypotension, which can result in falls and fractures. Few studies have assessed the risk of hip fracture due to mirtazapine, and no known studies have assessed whether the risk of hip fracture is higher in patients taking other antidepressant medicines in combination with mirtazapine. Objectives: This study aimed to examine the risk of hip fracture in older people due to mirtazapine use as well as switching between or concurrently using mirtazapine and other antidepressants. Method: A matched case–control study was conducted. Cases were people aged over 65 years who were eligible for Australian Government Department of Veterans' Affairs (DVA) benefits and who sustained a hip fracture between 2009 and 2012. Each case was matched with up to four randomly selected controls of the same gender and age (± 2 years). Multivariable conditional logistic regression was used to estimate associations between antidepressant use and hip fracture. In order to assess whether combined antidepressant effects differed from the sum of individual effects, the relative excess risk due to interaction (RERI) was calculated. Results: The study population comprised 8828 cases and 35,310 controls. The median age of these participants was 88 years and 63% were women. The risk of hip fracture was increased for mirtazapine (continuous use: odds ratio [OR] 1.27, 95% confidence interval [CI] 1.12–1.44). The combinations associated with increased odds of hip fracture were addition of selective serotonin reuptake inhibitors (SSRIs) to mirtazapine (OR 11, 95% CI 2.2–51; RERI 7.7, 95% CI −9.0 to 24), addition of tricyclic antidepressants (TCAs) to mirtazapine (OR 14, 95% CI 1.4–132; RERI 12, 95% CI −19 to 43) and continuous use of both SSRIs and mirtazapine (OR 2.4, 95% CI 1.4–4.2; RERI 0.4, 95% CI −0.9 to 1.7). RERIs indicated that the effect of each antidepressant pair equalled the sum of the effects of individual antidepressant use. There was no evidence of ...

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. ...

Abstract Background To compare the results of a new-user cohort study design and the self-controlled case series (SCCS) design using the risk of hospitalisation for pneumonia in those dispensed proton pump inhibitors compared to those unexposed as a case study. Methods The Australian Government Department of Veterans' Affairs administrative claims database was used. Exposure to proton pump inhibitors and hospitalisations for pneumonia were identified over a 4 year study period 01 Jul 2007 -30 Jun 2011. The same inclusion and exclusion criteria were applied to both studies, however, the SCCS study included subjects with a least one hospitalisation for pneumonia. Results There were 105,467 subjects included in the cohort study and 6775 in the SCCS. Both studies showed an increased risk of hospitalisations for pneumonia in the three defined risk periods following initiation of proton pump inhibitors compared to baseline. With the highest risk in the first 1 to 7 days (Cohort RR, 3.24; 95% CI (2.50, 4.19): SCCS: RR, 3.07; 95% CI (2.69, 3.50)). Conclusions This study has shown that the self-controlled case series method produces similar risk estimates to a new-users cohort study design when applied to the association of proton pump inhibitors and pneumonia. Exposure to a proton pump inhibitor increases the likelihood of being admitted to hospital for pneumonia, with the risk highest in the first week of treatment.

OBJECTIVE: To 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 PARTICIPANTS: Retrospective 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 MEASURES: The 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. RESULTS: In 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%. CONCLUSIONS: Opioid 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.

Abstract Background To determine the suitability of using the self-controlled case series design to assess improvements in health outcomes using the effectiveness of beta blockers for heart failure in reducing hospitalisations as the example. Methods The Australian Government Department of Veterans' Affairs administrative claims database was used to undertake a self-controlled case-series in elderly patients aged 65 years or over to compare the risk of a heart failure hospitalisation during periods of being exposed and unexposed to a beta blocker. Two studies, the first using a one year period and the second using a four year period were undertaken to determine if the estimates varied due to changes in severity of heart failure over time. Results In the one year period, 3,450 patients and in the four year period, 12, 682 patients had at least one hospitalisation for heart failure. The one year period showed a non-significant decrease in hospitalisations for heart failure 4-8 months after starting beta-blockers, (RR, 0.76; 95% CI (0.57-1.02)) and a significant decrease in the 8-12 months post-initiation of a beta blocker for heart failure (RR, 0.62; 95% CI (0.39, 0.99)). For the four year study there was an increased risk of hospitalisation less than eight months post-initiation and significant but smaller decrease in the 8-12 month window (RR, 0.90; 95% CI (0.82, 0.98)). Conclusions The results of the one year observation period are similar to those observed in randomised clinical trials indicating that the self-controlled case-series method can be successfully applied to assess health outcomes. However, the result appears sensitive to the study periods used and further research to understand the appropriate applications of this method in pharmacoepidemiology is still required. The results also illustrate the benefits of extending beta blocker utilisation to the older age group of heart failure patients in which their use is common but the evidence is sparse.

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02010-z.

Background: Multiple studies have assessed the appropriateness of the use of medicines for nursing home residents; however, few have included duration of use in their assessment. The aim of this study was to assess the level and duration of use of medications recommended for short-term use in residents of aged care facilities in Australia. Methods: Australian Government Department of Veterans' Affairs (DVA) administrative claims data were used for this study. Veterans eligible for all health services subsidised by DVA were followed for one year from 1 July 2015 to 30 June 2016. The number of days covered for each medicine was calculated by multiplying the number of prescriptions dispensed during the year by the pack duration for the medicine. The pack duration was calculated by dividing the quantity supplied at each dispensing by the usual number of doses per day in older people according to Australian prescribing guidelines. The proportion of patients using each medicine and the number of days covered during the study period were determined. Results: 14, 237 residents met the inclusion criteria. One in five participants were dispensed antipsychotics, and the median duration of use was 180 days in the one-year period. More than one-third were dispensed a benzodiazepine, and the median duration of use was 240 days in the year. Half were dispensed an opioid analgesic with a median duration of use of 225 days in the year. Fifty-two percent were dispensed proton pump inhibitors with a median duration of use of 360 days in the year. A quarter received an antibiotic recommended for the management of urinary tract infection, with a median duration of use of 14 days in the year. Conclusion: Long-term use of antipsychotics, benzodiazepines, opioid analgesics and proton pump inhibitors is common in aged care residents. Ensuring appropriate duration of use for these medicines is necessary to reduce risk of harm.

Background: Risperidone is the only antipsychotic approved in Australia for the management of the behavioural and psychological symptoms of dementia (BPSD). In June 2015, the Australian Government Therapeutic Goods Administration (TGA) amended the indication to restrict use in BPSD to patients with Alzheimer's dementia for a maximum twelve-week duration. We aimed to determine whether the rate and duration of risperidone use for BPSD decreased following the regulatory changes. Methods: we conducted a study using the Australian Government Department of Veterans' Affairs administrative claims data and Pharmaceutical Benefits Scheme (PBS) 10% sample data. We included people aged 65 years or older and compared the rate and duration of risperidone use before and after the TGA labelling changes. Results: There was a sustained decrease in the trend of risperidone use for BPSD following the TGA labelling changes, with a monthly decrease of 1.7% in the aged care population, 0.5% in the community living population and 1.5% in the general older Australian population. Overall, in the 24 months post the TGA changes the reduction in the rate of use of risperidone ranged from 20% to 28% lower than compared to what the rate would have been without the TGA changes. The median duration of use of risperidone in aged-care residents decreased from 338 days in the year prior to the TGA labelling changes, to 240 days per person in the year after the changes. Conclusion: The TGA labelling changes were associated with a significant reduction in the rate of use of risperidone for BPSD in veterans living in both the aged care and community settings, and in the general older Australian population. The labelling changes were also associated with a reduced duration of risperidone use in aged care residents, although for most people the duration of use still exceeded the recommended 12-week maximum duration.

OBJECTIVES: The 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. DESIGN: Sequential 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. SETTING: Australian Government Department of Veterans' Affairs claims database. PARTICIPANTS: 4836 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 MEASURES: One-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. RESULTS: Using 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. CONCLUSION: We found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.

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.

Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (https://creativecommons.org/licenses/by-nc/3.0) ; Background and purpose — It is unclear whether metal particles and ions produced by mechanical wear and corrosion of hip prostheses with metal-on-metal (MoM) bearings have systemic adverse effects on health. We compared the risk of heart failure in patients with conventional MoM total hip arthroplasty (THA) and in those with metal-on-polyethylene (MoP) THA. Patients and methods — We conducted a retrospective cohort study using data from the Australian Government Department of Veterans' Affairs health claims database on patients who received conventional THA for osteoarthritis between 2004 and 2012. The MoM THAs were classified into groups: Articular Surface Replacement (ASR) XL Acetabular System, other large-head (LH) (> 32 mm) MoM, and small-head (SH) (≤ 32 mm) MoM. The primary outcome was hospitalization for heart failure after THA. Results — 4,019 patients with no history of heart failure were included (56% women). Men with an ASR XL THA had a higher rate of hospitalization for heart failure than men with MoP THA (hazard ratio (HR) = 3.2, 95% CI: 1.6–6.5). No statistically significant difference in the rate of heart failure was found with the other LH MoM or SH MoM compared to MoP in men. There was no statistically significant difference in heart failure rate between exposure groups in women. Interpretation — An association between ASR XL and hospitalization for heart failure was found in men. While causality between ASR XL and heart failure could not be established in this study, it highlights an urgent need for further studies to investigate the possibility of systemic effects associated with MoM THA.

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

Objective: To provide insights into complexities of seeking access to state and federal cross-jurisdictional 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.

Abstract 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.