Trajectories of oral bisphosphonate use after hip fractures: a population-based cohort study.

Bisphosphonates prevent future hip fractures. However, we found that one in six patients with hip fractures had a delay in bisphosphonate initiation and another one-sixth discontinued treatment within 12 months after discharge. Our results highlight the need to address hesitancy in treatment initiation and continuous monitoring. PURPOSE: Suboptimal antiresorptive use is not well understood. This study investigated trajectories of oral bisphosphonate use following first hip fractures and factors associated with different adherence and persistence trajectories. METHODS: We conducted a retrospective study of all patients aged ≥ 50 years dispensed two or more bisphosphonate prescriptions following first hip fracture in Victoria, Australia, from 2012 to 2017. Twelve-month trajectories of bisphosphonate use were categorized using group-based trajectory modeling. Factors associated with different trajectories compared to the persistent adherence trajectory were assessed using multivariate multinomial logistic regression. RESULTS: We identified four patterns of oral bisphosphonate use in 1811 patients: persistent adherence (66%); delayed dispensing (17%); early discontinuation (9%); and late discontinuation (9%). Pre-admission bisphosphonate use was associated with a lower risk of delayed dispensing in both sexes (relative risk [RR] 0.28, 95% confidence interval [CI] 0.21-0.39). Older patients ( ≥ 85 years old versus 50-64 years old, RR 0.38, 95% CI 0.22-0.64) had a lower risk of delayed dispensing. Males with anxiety (RR 9.80, 95% CI 2.24-42.9) and females with previous falls had increased risk of early discontinuation (RR 1.80, 95% CI 1.16-2.78). CONCLUSION: Two-thirds of patients demonstrated good adherence to oral bisphosphonates over 12 months following hip fracture. Efforts to further increase post-discharge antiresorptive use should be sex-specific and address possible persistent uncertainty around delaying treatment initiation.

Future Burden of Ischemic Stroke in Australia: Impact on Health Outcomes between 2019 and 2038.

BACKGROUND: Projections of the future burden of ischemic stroke (IS) has not been extensively reported for the Australian population; the availability of such data would assist in health policy planning, clinical guideline updates, and public health. METHODS: First, we estimated the lifetime risk of IS (from age 40 to 100 years) using a multistate life table model. Second, a dynamic multistate model was constructed to project the burden of IS for the whole Australian population aged between 40 and 100 years over a 20-year period (2019-2038). Data for the study were primarily sourced from a large, representative Victorian linked dataset based on the Victorian Admitted Episode Dataset and National Death Index. The model projected prevalent and incident cases of nonfatal IS, fatal IS, and years of life lived (YLL) with and without IS. The YLL outcome was discounted by 5% annually; we varied the discounting rate in scenario analyses. RESULTS: The lifetime risk of IS from age 40 years was estimated as 15.5% for males and 14.0% for females in 2018. From 2019 to 2038, 644,208 Australians were projected to develop incident IS (564,922 nonfatal and 79,287 fatal). By 2038, the model projected there would be 358,534 people with prevalent IS, 35,554 people with incident nonfatal IS and 5,338 people with fatal IS, a 14.2% (44,535), 72.9% (14,988), and 106.3% (2,751) increase compared to 2019 estimations, respectively. Projected YLL (with a 5% discount rate) accrued by the Australian population were 174,782,672 (84,251,360 in males and 90,531,312 in females), with 4,053,794 YLL among people with IS (2,320,513 in males, 1,733,281 in females). CONCLUSION: The burden of IS was projected to increase between 2019 and 2038 in Australia. The outcomes of the model provide important information for decision-makers to design strategies to reduce stroke burden.

Current and Future Cost Burden of Ischemic Stroke in Australia: Dynamic Model.

BACKGROUND: Stroke remains one of the leading causes of morbidity and mortality in Australia. The objective of this study was to estimate the current and future cost burden of ischemic stroke (IS) in Australia. METHOD: First, chronic management costs following IS were derived for all people aged ≥ 30 years discharged from a public or private hospital in Victoria, Australia between July 2012 and June 2017 (n = 34 471). These costs were then used to project total costs following IS (combination of acute event and chronic management cost) over a 20-year period (2019-2038) for people aged between 30 and 99 years in Australia using a dynamic multistate lifetable model. Data for the dynamic model were sourced from the Victorian Admitted Episodes Dataset (VAED) and supplemented with other published data. RESULT: The estimated annual total chronic management cost following IS was 13 525 Australian dollars (AUD) per person (95%CI: AUD 13 380, AUD 13 670) for cohorts in the VAED between July 2012 and June 2017. The annual chronic management cost was estimated to decline following IS. The highest cost was incurred in the first year of follow-up post-IS (AUD 14 309 per person) and declined to AUD 9 776 in the sixth year of follow-up post-IS. The total healthcare cost for people aged 30-99 years was projected to be AUD 47.7 billion (95% UI: AUD 44.6 billion, AUD 51.0 billion) over the 20-year period (2019-2038) Australia-wide, of which 91.3% (AUD 43.6 billion) was attributed to chronic management costs and the remaining 8.7% (AUD 4.2 billion) were due to acute IS events. CONCLUSION: IS has and will continue to have a considerable financial impact in the next two decades on the Australian healthcare system. Our estimated and projected cost burden following IS provides important information for decision making in relation to IS.

Acute kidney injury, renal impairment and renal failure associated with sodium glucose co-transporter-2 inhibitors in at-risk groups: A systematic review.

Randomized controlled trials (RCTs) show a reduction in acute kidney injury, renal impairment and acute renal failure after initiation of a sodium glucose cotransporter-2 inhibitor. Observational literature on the association is conflicting, but important to understand for populations with a higher risk of medication-related adverse renal events. We aimed to systematically review the literature to summarize the association between sodium glucose cotransporter-2 inhibitor use and acute kidney injury, renal impairment and acute renal failure in three at-risk groups: older people aged >65 years, people with heart failure and people with reduced renal function. A systematic search of Embase (1974 until 23 February 2024) and PubMed (1946 until 23 February 2024) was performed. RCTs were included if they reported numbers of acute kidney injury or acute renal failure in people using sodium glucose cotransporter-2 inhibitors compared to other diabetic therapies. Studies needed to report results by level of renal function, heart failure status or age. Of 922 results, eight studies were included. The absolute risk of acute kidney injury or acute renal failure was higher in people >65 years compared to those <65 years, higher in people with heart failure (vs without) and higher in people with reduced kidney function (vs preserved kidney function), but insufficient evidence to determine if the relative effect of sodium glucose cotransporter-2 inhibitors on this risk was similar for each group. At-risk cohorts are associated with a higher incidence of acute kidney problems in users of sodium glucose cotransporter-2 inhibitors.

Trajectories of prescription opioid tapering in patients with chronic non-cancer pain: a retrospective cohort study, 2015-2020.

OBJECTIVE: To identify common opioid tapering trajectories among patients commencing opioid taper from long-term opioid therapy for chronic non-cancer pain and to examine patient-level characteristics associated with these different trajectories. DESIGN: A retrospective cohort study. SETTING: Australian primary care. SUBJECTS: Patients prescribed opioid analgesics between 2015 and 2020. METHODS: Group-based trajectory modeling and multinomial logistic regression analysis were conducted to determine tapering trajectories and to examine demographic and clinical factors associated with the different trajectories. RESULTS: A total of 3369 patients commenced a taper from long-term opioid therapy. Six distinct opioid tapering trajectories were identified: low dose / completed taper (12.9%), medium dose / faster taper (12.2%), medium dose / gradual taper (6.5%), low dose / noncompleted taper (21.3%), medium dose / noncompleted taper (30.4%), and high dose / noncompleted taper (16.7%). A completed tapering trajectory from a high opioid dose was not identified. Among patients prescribed medium opioid doses, those who completed their taper were more likely to have higher geographically derived socioeconomic status (relative risk ratio [RRR], 1.067; 95% confidence interval [CI], 1.001-1.137) and less likely to have sleep disorders (RRR, 0.661; 95% CI, 0.463-0.945) than were those who didn't complete their taper. Patients who didn't complete their taper were more likely to be prescribed strong opioids (eg, morphine, oxycodone), regardless of whether they were tapered from low (RRR, 1.444; 95% CI, 1.138-1.831) or high (RRR, 1.344; 95% CI, 1.027-1.760) doses. CONCLUSIONS: Those prescribed strong opioids and high doses appear to be less likely to complete tapering. Further studies are needed to evaluate the clinical outcomes associated with the identified trajectories.

Patterns of 12-Month Post-Myocardial Infarction Medication Use According to Revascularisation Strategy: Analysis of 15,339 Admissions in Victoria, Australia.

AIM: Clinical guidelines recommend secondary prevention medications following myocardial infarction (MI) regardless of revascularisation strategy. Studies suggest that there is variation in post-MI medication use following percutaneous coronary intervention (PCI) and coronary artery bypass grafts (CABG). We investigated initial dispensing and 12-month patterns of medication use according to revascularisation strategy following non-ST-elevation MI (NSTEMI). METHOD: We included all public and private hospital admissions for NSTEMI for patients aged ≥30 years in Victoria, Australia, between July 2012 and June 2017. We investigated initial dispensing of P2Y12 inhibitors (P2Y12i), statins (total and high intensity), angiotensin-converting-enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), and beta blockers within 60 days after discharge. Twelve-month post-MI medication use was estimated as the proportion of days covered (PDC) over a 12-month period from the date of hospital discharge. Analyses were performed using adjusted regression models, stratified by revascularisation strategy. RESULTS: There were 15,399 admissions for NSTEMI: 11,754 with PCI and 3,645 with CABG. Following adjustments, predicted probability of initial dispensing in the PCI and CABG groups, respectively, was 0.94 (95% confidence interval 0.93-0.95) vs 0.17 (0.13-0.21) for P2Y12i; 0.69 (0.66-0.71) vs 0.42 (0.37-0.48) for ACEi/ARB; 0.59 (0.57-0.62) vs 0.69 (0.64-0.74) for beta blockers; 0.89 (0.87-0.91) vs 0.89 (0.85-0.92) for statins; and 0.60 (0.57-0.62) vs 0.69 (0.63-0.73) for high intensity statins. The 12-month PDC in the PCI and CABG groups, respectively, was 0.82 (0.80-0.83) vs 0.12 (0.09-0.15) for P2Y12i; 0.62 (0.60-0.65) vs 0.43 (0.39-0.48) for ACEi/ARB; 0.53 (0.51-0.55) vs 0.632 (0.58-0.66) for beta blockers; 0.79 (0.78-0.81) vs 0.78 (0.74-0.81) for statins; and 0.49 (0.47-0.51) vs 0.55 (0.50-0.59) for high intensity statins. CONCLUSIONS: Post-discharge dispensing of secondary prevention medications differed with respect to revascularisation strategy from 2012 to 2017, despite clear evidence of benefit during this period. Interventions may be needed to address possible clinician and patient uncertainty about the benefits of secondary prevention medications, regardless of revascularisation strategy.

COVID-19 restrictions and the incidence and prevalence of prescription opioid use in Australia - a nationwide study.

The COVID-19 pandemic has disrupted seeking and delivery of healthcare. Different Australian jurisdictions implemented different COVID-19 restrictions. We used Australian national pharmacy dispensing data to conduct interrupted time series analyses to examine the incidence and prevalence of opioid dispensing in different jurisdictions. Following nationwide COVID-19 restrictions, the incidence dropped by -0.40 (95% confidence interval [CI]: -0.50, -0.31), -0.33 (95% CI: -0.46, -0.21) and -0.21 (95% CI: -0.37, -0.04) per 1000 people per week and the prevalence dropped by -0.85 (95% CI: -1.39, -0.31), -0.54 (95% CI: -1.01, -0.07) and -0.62 (95% CI: -0.99, -0.25) per 1000 people per week in Victoria, New South Wales and other jurisdictions, respectively. Incidence and prevalence increased by 0.29 (95% CI: 0.13, 0.44) and 0.72 (95% CI: 0.11, 1.33) per 1000 people per week, respectively in Victoria post-lockdown; no significant changes were observed in other jurisdictions. No significant changes were observed in the initiation of long-term opioid use in any jurisdictions. More stringent restrictions coincided with more pronounced reductions in overall opioid initiation, but initiation of long-term opioid use did not change.

Dispensing of psychotropic medications to Australian children and adolescents before and during the COVID-19 pandemic, 2013-2021: a retrospective cohort study.

OBJECTIVE: To determine longitudinal patterns of dispensing of antidepressant, anxiolytic, antipsychotic, psychostimulant, and hypnotic/sedative medications to children and adolescents in Australia during 2013-2021. DESIGN: Retrospective cohort study; analysis of 10% random sample of Pharmaceutical Benefits Scheme (PBS) dispensing data. PARTICIPANTS, SETTING: People aged 18 years or younger dispensed PBS-subsidised psychotropic medications in Australia, 2013-2021. MAIN OUTCOME MEASURES: Population prevalence of dispensing of psychotropic medications to children and adolescents, by psychotropic class, gender, and age group (0-6, 7-12, 13-18 years). RESULTS: The overall prevalence of psychotropic dispensing to children and adolescents was 33.8 per 1000 boys and 25.2 per 1000 girls in 2013, and 60.0 per 1000 boys and 48.3 per 1000 girls in 2021. The prevalence of psychotropic polypharmacy was 5.4 per 1000 boys and 3.7 per 1000 girls in 2013, and 10.4 per 1000 boys and 8.3 per 1000 girls in 2021. Prevalent dispensing during 2021 was highest for psychostimulants (boys, 44.0 per 1000; girls, 17.4 per 1000) and antidepressants (boys, 20.4 per 1000; girls, 33.8 per 1000). During 2021, the prevalence of dispensing was higher than predicted by extrapolation of 2013-2019 data for many classes, including antidepressants (boys: +6.1%; 95% CI, 1.1-11.1%; girls: +22.2%; 95% CI, 17.4-26.9%), and psychostimulants (boys: +14.5%; 95% CI, 8.0-21.1%; girls: +27.7%; 95% CI, 18.9-36.6%). The increases were greatest for girls aged 13-18 years (antidepressants: +20.3%; 95% CI, 16.9-23.7%; psychostimulants: +39.0%; 95% CI, 27.9-50.0%). CONCLUSIONS: The prevalence of both psychotropic dispensing and psychotropic polypharmacy for children and adolescents were twice as high in 2021 as in 2013. The reasons and appropriateness of the marked increases in psychotropic dispensing during the COVID-19 pandemic, particularly to adolescent girls, should be investigated.

Preferences for deprescribing antihypertensive medications amongst clinicians, carers and people living with dementia: a discrete choice experiment.

BACKGROUND: Optimal management of hypertension in people with dementia may involve deprescribing antihypertensives. Understanding differing treatment priorities is important to enable patient-centred care. This study explored preferences for antihypertensive deprescribing amongst people living with dementia, carers and clinicians. METHODS: Discrete choice experiments (DCEs) are a stated preference survey method, underpinned by economic theory. A DCE was conducted, and respondents completed 12 labelled choice-questions, each presenting a status quo (continuing antihypertensives) and antihypertensive deprescribing option. The questions included six attributes, including pill burden, and event risks for stroke, myocardial infarction, increased blood pressure, cognitive decline, falls. RESULTS: Overall, 112 respondents (33 carers, 19 people living with dementia, and 60 clinicians) completed the survey. For people with dementia, lower pill burden increased preferences for deprescribing (odds ratio (OR) 1.95, 95% confidence interval (95% CI) 1.08-3.52). Increased stroke risk (for each additional person out of 100 having a stroke) decreased the likelihood of deprescribing for geriatricians (OR 0.71, 95% CI 0.55-0.92) and non-geriatrician clinicians (OR 0.62, 95% CI 0.45-0.86), and carers (OR 0.71, 95% CI 0.58-0.88). Increased myocardial infarction risk decreased preferences for deprescribing for non-geriatricians (OR 0.81, 95% CI 0.69-0.95) and carers (OR 0.84, 95% CI 0.73-0.98). Avoiding cognitive decline increased preferences for deprescribing for geriatricians (OR 1.17, 95% CI 1.03-1.33) and carers (OR 1.27, 95% CI 1.09-1.48). Avoiding falls increased preferences for deprescribing for clinicians (geriatricians (OR 1.20, 95% CI 1.11-1.29); non-geriatricians (OR 1.16, 95% CI 1.07-1.25)). Other attributes did not significantly influence respondent preferences. CONCLUSIONS: Antihypertensive deprescribing preferences differ amongst people with dementia, carers and clinicians. The study emphasises the importance of shared decision-making within the deprescribing process.

Trends of polypharmacy among older people in Asia, Australia and the United Kingdom: a multinational population-based study.

BACKGROUND: Polypharmacy among older people represents a global challenge due to its association with adverse drug events. The reported prevalence of polypharmacy varies widely across countries, and is particularly high in Asian countries. However, there is no multinational study using standardised measurements exploring variations in prescribing trends. OBJECTIVE: To compare polypharmacy trends in older people in Asia, Australia and the United Kingdom. DESIGN: Multinational, retrospective, time-trend, observational study using a common study protocol. SETTING: Outpatient and community settings. SUBJECTS: All individuals aged ≥ 65 years between 2013 and 2016. METHODS: We defined polypharmacy as the concomitant use of ≥5 medications for ≥45 days per year. We estimated the annual prevalence of polypharmacy and calculated average annual percentage change (AAPC) to assess the time trends. RESULTS: A total of 1.62 million individuals were included in this study. The highest prevalence of polypharmacy was observed in Hong Kong (46.4%), followed by Taiwan (38.8%), South Korea (32.0%), the United Kingdom (23.5%) and Australia (20.1%) in 2016. For the time trend, the Asian region showed a steady increase, particularly in Hong Kong and South Korea (AAPC: Hong Kong, 2.7%; South Korea, 1.8%; Taiwan, 1.0%). However, Australia and the United Kingdom showed a decreasing trend (Australia, -4.9%; the United Kingdom, -1.1%). CONCLUSIONS: Polypharmacy prevalence in older people was higher in Hong Kong, Taiwan and South Korea, with an increasing trend over time, compared with Australia and the United Kingdom. Our findings underline the necessity to monitor polypharmacy among older people in Asia by conducting government-level interventions and introducing medicine-optimisation strategies.

Depression and anxiety prevalence in people with cystic fibrosis and their caregivers: a systematic review and meta-analysis.

BACKGROUND: Prevalence of depression and anxiety in people with cystic fibrosis (PwCF) and their caregivers is high, however, results have been inconsistent. This systematic review and meta-analysis aimed to estimate the prevalence of depression and anxiety in PwCF and their caregivers and explore sources of heterogeneity. METHOD: MEDLINE, EMBASE, CINAHL plus and PsychINFO databases were searched from inception to January 2021. Studies were included if a specific psychometric tool (PT) to assess depression or anxiety (rather than quality of life) was used and did not involve a transitory patient state. Random-effects models were applied due to high anticipated heterogeneity and I2 estimates were calculated. Sources of heterogeneity were explored through subgroup comparisons. The presence of small-study effects was investigated visually using funnel plots and statistically using the Egger test. RESULTS: A total of 94 articles (48 full-text publications, 46 abstracts) were included. Depression prevalence in adolescents aged 12-18 years (n = 2386), adults (n = 9206) and caregivers (n = 6617) were 18.7% (95% CI 12.8-25.3%, I2 = 89.2%), 27.2% (95% CI 23.6-31%, I2 = 90.4%), and 32.8% (95% CI 27.9-37.9%, I2 = 90.3%), respectively. Anxiety prevalence in adolescents aged 12-18 years (n = 2142) was 26% (95% CI 19.6-33%, I2 = 86.4%), 28.4% (95% CI 25-31.9%, I2 = 85%) for adults (n = 8175), and 38.4% (95% CI 30.8-46.2%, I2 = 94.6%) for caregivers (n = 5931). Prevalence differed by the PT used and study location. DISCUSSION: This comprehensive analysis found the prevalence of depression and anxiety in PwCF and their caregivers to be high, supporting recommendations for regular screening. Choice of PT significantly influenced prevalence, indicating a need for future studies to identify the optimal PT for each CF population to identify those most at risk.

Temporal and age-specific trends in incidence and 1-year case-fatality of hospitalized ischaemic stroke in Victoria, Australia.

OBJECTIVES: Investigate temporal and age-specific trends in the incidence of ischaemic stroke and case-fatality risk in Victoria, Australia. MATERIALS AND METHODS: Patients hospitalised with first ischaemic stroke between 2012 and 2018 were included. Trends in age-standardised incidence rates of ischaemic stroke were assessed using linear regression models. Cox proportional hazard regression models were used to examine the case-fatality risk. RESULTS: Overall age-standardised incidence of ischaemic stroke was stable from 2012/13 to 2017/18 (87.6 to 84.8 events per 100,000 population; Annual percentage change [APC] -0.32; 95% Confidence interval [CI] -1.13 to 0.50). The incidence declined in females (APC -1.00; 95% CI -1.49 to -0.50), people aged 75-84 years (APC -1.60; 95% CI -2.83 to -0.36) and in metropolitan areas (APC -0.74; 95% CI -1.02 to -0.45). The risk of 1-year case-fatality (HR 0.85; 95% CI 0.78 to 0.93) significantly declined in 2016/17 compared to 2012/13. CONCLUSIONS: Overall ischaemic stroke incidence remained stable while decreasing trends were observed in females, elderly and metropolitan areas. 1-year case-fatality declined from 2012 to 2017.

A Systems-Based Analysis of Mono- and Combination Therapy for Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections.

Antimicrobial resistance is a global threat. As "proof-of-concept," we employed a system-based approach to identify patient, bacterial, and drug variables contributing to mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKp) bloodstream infections exposed to colistin (COL) and ceftazidime-avibactam (CAZ/AVI) as mono- or combination therapies. Patients (n = 49) and CRKp isolates (n = 22) were part of the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a multicenter, observational, prospective study of patients with carbapenem-resistant Enterobacterales (CRE) conducted between 2011 and 2016. Pharmacodynamic activity of mono- and combination drug concentrations was evaluated over 24 h using in vitro static time-kill assays. Bacterial growth and killing dynamics were estimated with a mechanism-based model. Random Forest was used to rank variables important for predicting 30-day mortality. Isolates exposed to COL+CAZ/AVI had enhanced early bacterial killing compared to CAZ/AVI alone and fewer incidences of regrowth compared to COL and CAZ/AVI. The mean coefficient of determination (R2) for the observed versus predicted bacterial counts was 0.86 (range: 0.75 - 0.95). Bacterial subpopulation susceptibilities and drug mechanistic synergy were essential to describe bacterial killing and growth dynamics. The combination of clinical (hypotension), bacterial (IncR plasmid, aadA2, and sul3) and drug (KC50) variables were most predictive of 30-day mortality. This proof-of-concept study combined clinical, bacterial, and drug variables in a unified model to evaluate clinical outcomes.

Switching, Persistence and Adherence to Statin Therapy: a Retrospective Cohort Study Using the Australian National Pharmacy Data.

BACKGROUND: Statins are widely prescribed for the primary and secondary prevention of cardiovascular disease (CVD), but their effectiveness is dependent on the level of adherence and persistence. OBJECTIVES: This study aimed to explore the patterns of switching, adherence and persistence among the Australian general population with newly dispensed statins. METHODS: A retrospective cohort study was conducted using a random sample of data from the Australian national prescription claims data. Switching, adherence to and persistence with statins were assessed for people starting statins from 1 January 2015 to 31 December 2019. Switching was defined as either switching to another intensity of statin, to another statin or to a non-statin agent. Non-persistence to treatment was defined as discontinuation (i.e. ≥90 days with no statin) of coverage. Adherence was measured using proportion of days covered (PDC), and patients with PDC < 0.80 were considered non-adherent. Cox proportional hazard models were used to compare discontinuation, switching and reinitiation between different statins. RESULTS: A cohort of 141,062 people dispensed statins and followed over a median duration of 2.5 years were included. Of the cohort, 29.3% switched statin intensity, 28.4% switched statin type, 3.7% switched to ezetimibe and in 2.7%, ezetimibe was added as combination therapy during the study period. Overall, 58.8% discontinued statins based on the 90-day gap criteria, of whom 55.2% restarted. The proportion of people non-adherent was 24.0% at 6 months to 49.0% at 5 years. People on low and moderate intensity statins were more likely to discontinue compared to those on high-intensity statins (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.31), (HR 1.28, 95%CI 1.14-1.42), respectively. Compared to maintaining same statin type and intensity, switching statins, which includes up-titration (HR 0.77, 95%CI 0.70 to 0.86) was associated with less likelihood of discontinuation after reinitiation. CONCLUSIONS: Long-term persistence and adherence to statins remains generally poor among Australians, which limits the effectiveness of these medicines and the consequent health impact they may provide for individuals (and by extension, the population impact when poor persistence and adherence is considered in the statin-taking population). Switching between statins is prevalent in one third of statin users, although any clinical benefit of the observed switching trend is unknown. This, combined with the high volume of statin prescriptions, highlights the need for better strategies to address poor persistence and adherence.

Validity of three risk prediction models for dementia or cognitive impairment in Australia.

BACKGROUND: no studies have compared the predictive validity of different dementia risk prediction models in Australia. OBJECTIVES: (i) to investigate the predictive validity of the Australian National University-Alzheimer's Disease Risk Index (ANU-ADRI), LIfestyle for BRAin Health (LIBRA) Index and cardiovascular risk factors, ageing and dementia study (CAIDE) models for predicting probable dementia/cognitive impairment in an Australian cohort. (ii) To develop and assess the predictive validity of a new hybrid model combining variables from the three models. METHODS: the Hunter Community Study (HCS) included 3,306 adults aged 55-85 years with a median follow-up of 7.1 years. Probable dementia/cognitive impairment was defined using Admitted Patient Data Collection, dispensing of cholinesterase inhibitors or memantine, or a cognitive test. Model validity was assessed by calibration and discrimination. A hybrid model was developed using deep neural network analysis, a machine learning method. RESULTS: 120 (3.6%) participants developed probable dementia/cognitive impairment. Mean calibration by ANU-ADRI, LIBRA, CAIDE and the hybrid model was 19, 0.5, 4.7 and 3.4%, respectively. The discrimination of the models was 0.65 (95% CI 0.60-0.70), 0.65 (95% CI 0.60-0.71), 0.54 (95% CI 0.49-0.58) and 0.80 (95% CI 0.78-0.83), respectively. CONCLUSION: ANU-ADRI and LIBRA were better dementia prediction tools than CAIDE for identification of high-risk individuals in this cohort. ANU-ADRI overestimated and LIBRA underestimated the risk. The new hybrid model had a higher predictive performance than the other models but it needs to be validated independently in longitudinal studies.

Treatment initiation for parkinson's disease in Australia 2013-2018: a nation-wide study.

BACKGROUND: Guidelines highlight the importance of an individualized approach to treatment initiation for Parkinson's disease. Our aim was to investigate initiation of anti-Parkinson medication in Australia from 2013-2018, and to determine factors predicting choice of initial treatment. METHODS: Cohort of new-users (N = 4,887) of anti-Parkinson medication aged ≥ 40 years were identified from a 10% random representative sample of national medication dispensing data from July-2013 to June-2018. Changes in treatment initiation were examined across the whole cohort and stratified by age and sex. RESULTS: Treatment initiation was most frequent with levodopa followed by non-ergot dopamine agonists (DAs) and anticholinergics. Two thirds initiated with levodopa across the study period. Initiation with non-ergot DAs increased from 22 to 27% (rate ratio, RR 1.23, 95% confidence interval, CI 1.02-1.47) and initiation with anticholinergics decreased from 6.9% to 2.4% (RR 0.34, 95% CI 0.21-0.55) from 2013-2018. Among persons aged ≥ 65 years, one third of women and one fourth of men initiated on levodopa. Among women aged < 65 years, rates of treatment initiation with DAs (37%) and levodopa (37%) were similar in 2013/2014 but initiation with DA exceeded levodopa thereafter. Among men aged < 65 years, treatment initiation with levodopa (44%-49%) remained more frequent than initiation with DAs (29%-32%) throughout the study period. CONCLUSIONS: Treatment initiation with levodopa was most frequent among persons aged ≥ 65 years, consistent with current guidelines. Whilst the value of levodopa sparing strategies is unclear, treatment initiation with DA has become increasingly common relative to levodopa among women but not among men aged < 65 years.

Changes in use of hormonal long-acting reversible contraceptive methods in Australia between 2006 and 2018: A population-based study.

BACKGROUND: Long-acting reversible contraceptives (LARCs) are promoted internationally as a key strategy for reducing unintended pregnancy and abortion rates. AIMS: To examine trends in use of hormonal LARCs among reproductive-aged women in Australia between 2006 and 2018 and explore trends according to age groups and state/territory of dispensing. MATERIALS AND METHODS: Retrospective population-based study using Pharmaceutical Benefits Scheme (PBS) dispensing claims of a 10% random sample of females aged 15-44. We investigated rates and annual trends in dispensing claims of etonorgestrel implant and levonorgestrel intrauterine systems (IUS). RESULTS: Between 2006 and 2018, annual PBS claims for LARCs increased approximately two-fold from 21.7 to 41.5 per 1000 women, with a plateau observed from 2015 onward. Absolute rate increases were similar for the implant (9.0/1000) and IUS (10.8/1000), with increases observed across all age groups and states/territories. Overall dispensing rates varied by two-fold according to state/territory of dispensing and four-fold according to age groups. Rate increases for the implant were highest among the 15-19 and 20-24 age groups, while rate increases for the IUS were highest among the 35-39 and 40-44 age groups. It is estimated that in 2018, 10.8% of women aged 15-44 were using a LARC; 4.5% for the implant and 6.3% for the IUS. CONCLUSIONS: Rates of hormonal LARC use have doubled over the past decade. Investigating underlying reasons for the large observed differences in rates of use according to age and state/territory could help further improve uptake for these most effective methods of contraception.

Gastrointestinal bleeding risk with rivaroxaban vs aspirin in atrial fibrillation: A multinational study.

PURPOSE: Comparative gastrointestinal bleeding (GIB) risk between rivaroxaban and low-dose aspirin is unknown in patients with atrial fibrillation (AF). This study investigated GIB risk with rivaroxaban vs aspirin among two separate AF cohorts in Hong Kong and the United Kingdom, using a common protocol approach. METHODS: This was a population-based cohort study using separate data from the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority (2010-2018) and The Health Improvement Network (THIN) database in the United Kingdom (2011-2017). Patients with AF newly prescribed aspirin or rivaroxaban were included. Cox proportional hazards regression was used to compare GIB risks for rivaroxaban vs aspirin, accounting for confounders using propensity score fine stratification approach. RESULTS: In CDARS, 29 213 patients were included; n = 1052 (rivaroxaban), n = 28 161 (aspirin). Crude GIB event rates per 100 patient-years in CDARS were 3.0 (aspirin) and 2.6 (rivaroxaban). No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.04, 95%CI = 0.76-1.42), and in dose-stratified analyses (HR = 1.21, 95%CI = 0.84-1.74 [20 mg/day]; HR = 0.80, 95%CI = 0.44-1.45 [≤15 mg/day]). In THIN, 11 549 patients were included, n = 3496 (rivaroxaban) and n = 8053 (aspirin). Crude GIB event rates were 1.3 (aspirin) and 2.4 (rivaroxaban) per 100 patient-years. No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.40, 95%CI = 1.00-1.98) and low-dose rivaroxaban (≤15 mg/day) (HR = 1.00, 95%CI = 0.56-1.30), but increased GIB risk was observed for rivaroxaban 20 mg/day vs aspirin (HR = 1.57, 95%CI = 1.08-2.29). CONCLUSION: In patients with AF, GIB risk was comparable between aspirin and rivaroxaban ≤15 mg/day. GIB risk for rivaroxaban 20 mg/day vs aspirin remains uncertain and warrants further investigation.

Multiple antihypertensive use and risk of mortality in residents of aged care services: a prospective cohort study.

AIMS: The objective of this study is to investigate the association between multiple antihypertensive use and mortality in residents with diagnosed hypertension, and whether dementia and frailty modify this association. METHODS: This is a two-year prospective cohort study of 239 residents with diagnosed hypertension receiving antihypertensive therapy across six residential aged care services in South Australia. Data were obtained from electronic medical records, medication charts and validated assessments. The primary outcome was all-cause mortality and the secondary outcome was cardiovascular-related hospitalizations. Inverse probability weighted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. Covariates included age, sex, dementia severity, frailty status, Charlson's comorbidity index and cardiovascular comorbidities. RESULTS: The study sample (mean age of 88.1 ± 6.3 years; 79% female) included 70 (29.3%) residents using one antihypertensive and 169 (70.7%) residents using multiple antihypertensives. The crude incidence rates for death were higher in residents using multiple antihypertensives compared with residents using monotherapy (251 and 173/1000 person-years, respectively). After weighting, residents who used multiple antihypertensives had a greater risk of mortality compared with monotherapy (HR 1.40, 95%CI 1.03-1.92). After stratifying by dementia diagnosis and frailty status, the risk only remained significant in residents with diagnosed dementia (HR 1.91, 95%CI 1.20-3.04) and who were most frail (HR 2.52, 95%CI 1.13-5.64). Rate of cardiovascular-related hospitalizations did not differ among residents using multiple compared to monotherapy (rate ratio 0.73, 95%CI 0.32-1.67). CONCLUSIONS: Multiple antihypertensive use is associated with an increased risk of mortality in residents with diagnosed hypertension, particularly in residents with dementia and among those who are most frail.

Prevalence and incidence of prescription opioid analgesic use in Australia.

AIMS: The aims of the current study were to determine the prevalence and incidence of prescription opioid analgesic use in Australia and compare the characteristics of people with and without cancer initiating prescription opioid analgesics. METHODS: A retrospective population-based study was conducted using the random 10% sample of adults who were dispensed prescription opioid analgesics in Australia between July 2013 and June 2017 through the Pharmaceutical Benefits Scheme. Poisson regression was used to calculate rate ratios (RR) for opioid prevalence and incidence. The characteristics of people initiating opioids, including type of opioid initiated, total oral morphine equivalents dispensed, prescriber speciality, medical comorbidities, and past analgesic and benzodiazepine use, were compared for people with and without cancer. RESULTS: Opioid prevalence increased {RR = 1.006 [95% confidence interval (CI) 1.004, 1.008]}, while incidence decreased [RR = 0.977 (95% CI 0.975,0.979)] from 2013/2014 to 2016/2017. There were between 287 677 and 307 772 prevalent users each year. In total, 769 334 adults initiated opioids between 2013/2014 and 2016/2017, and half of these initiations were by general practitioners. Initiation with a strong opioid occurred in 55.8% of those with cancer and 28.2% of those without cancer. CONCLUSION: Rates of opioid use have remained high since 2013, with approximately 3 million adults using opioids and over 1.9 million adults initiating opioids each year. Between 2013 and 2017, opioid prevalence has slightly increased but incidence has decreased. People without cancer account for the majority of opioid use and are more likely to be initiated on short-acting and weak opioids. Initiation of strong opioids has increased over time, reinforcing concerns about increased use and the harms associated with strong opioids in the community.