Concurrent use of hormonal long-acting reversible contraception by women of reproductive age dispensed teratogenic medications, Australia, 2013-2021: a retrospective cohort study.

OBJECTIVES: To examine patterns in the dispensing of category X medications (Therapeutic Goods Administration categorisation system for prescribing medicines in pregnancy) to women aged 15-49 years in Australia during 2008-2021, and patterns of concurrent use of hormonal long-acting reversible contraception (LARC) and other hormonal contraception. STUDY DESIGN: Retrospective cohort study; analysis of 10% random sample of national Pharmaceutical Benefits Scheme dispensing data. PARTICIPANTS, SETTING: Women aged 15-49 years dispensed category X medications, Australia, 1 January 2013 - 31 December 2021. MAIN OUTCOME MEASURES: Incident and prevalent dispensing of category X medications, by medication class, age group, and year; contraceptive overlap (proportions of women dispensed hormonal LARC or other hormonal contraception that overlapped the first dispensing of category X medications), by medication class. RESULTS: Among 15 627 women aged 15-49 years dispensed category X medications during 2013-2021, the prevalence of dispensing increased from 4.6 in 2013 to 8.7 per 1000 women aged 15-49 years in 2021; the largest increase was for the dispensing of dermatological agents, from 3.9 to 7.9 per 1000 women aged 15-49 years. LARC overlap was inferred for 2059 women at the time of first dispensing of category X medications (13.2%); 3441 had been dispensed any type of hormonal contraception (22.1%). The proportion with LARC overlap was smallest for those dispensed dermatological agents (1806 of 14 331 women, 12.6%); for this drug class, both LARC overlap (adjusted odds ratio [aOR], 0.17; 95% confidence interval [CI], 0.14-0.20) and any hormonal contraception overlap (aOR, 0.28; 95% CI, 0.25-0.32) were less likely for those aged 15-19 years than for women aged 25-29 years. CONCLUSIONS: Concurrent use of highly effective hormonal contraception at the time of first dispensing of category X medications is low in Australia, raising concerns about potential fetal harms during unintended pregnancies. Awareness of the importance of hormonal contraception and its uptake by women prescribed category X medications should be increased.

Tree-based scan statistics to generate drug repurposing hypotheses: a test case using sodium-glucose cotransporter-2 inhibitors.

Most drug repurposing studies using real-world data focused on validating, instead of generating, hypotheses. We used tree-based scan statistics to generate repurposing hypotheses for sodium-glucose cotransporter-2 inhibitors (SGLT2i). We used an active-comparator, new-user design to create a 1:1 propensity-score matched cohort of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) initiators in the MerativeTM MarketScan® Research Databases. Tree-based scan statistics were estimated across an ICD-10-CM-based hierarchical outcome tree using incident outcomes identified from hospital and outpatient diagnoses. We used an adjusted P≤0.01 as the threshold for statistical alert to prioritize associations for evaluation as repurposing signals. We varied the analyses by tree size, scanning level, and clinical settings for outcomes. There were 80,510 matched SGLT2i-DPP4i initiator pairs with 215,333 outcomes among SGLT2i initiators and 223,428 outcomes among DPP4i initiators. There were 18 prioritized associations, which included chronic kidney disease (P=0.0001), an expected signal, and anemia (P=0.0001). Heart failure (P=0.0167), another expected signal, was identified slightly beyond the statistical alert threshold. Narrowing the outcome tree, scanning at different tree levels, and including outcomes from different clinical settings influenced the scan statistics. We identified signals aligning with recently approved indications of SGLT2i, plus potential repurposing signals supported by existing evidence but requiring future validation.

Prevalence of psychotropic medication dispensing to people living with cystic fibrosis in Australia: 2013-2022.

OBJECTIVE: People living with cystic fibrosis (PwCF) are at increased risk of mental health conditions. There is little evidence addressing psychotropic medication use in PwCF. This study aimed to estimate the dispensing prevalence of antidepressant, anxiolytic, antipsychotic, psychostimulant, and hypnotic/sedative medication in PwCF in Australia between 2013 and 2022. METHOD: A 10% random sample of Australian Pharmaceutical Benefits Scheme data was used to identify PwCF and their medications between 2013 and 2022. Annual prevalence of psychotropic medication dispensing was estimated using a 3-year rolling average, stratified by sex, age, and medication class. RESULTS: Psychotropic medications were dispensed to 206/478 (41.3%) PwCF. Antidepressant and anxiolytic dispensing prevalence was highest in adult females, increasing from 201 5 by 50% to their peak in 2021 (antidepressants 36.8%; anxiolytics 12.3%). Psychostimulant prevalence was highest in adolescent males and increased over three-fold during the study period from 3.6% to 13.2%. The prevalence of antipsychotic medication was lower than other classes with adult females having the highest prevalence (3.1% and 5.8% in 201 5 and 2022 respectively). Hypnotic/sedative medications remained consistently low or decreased in all groups except male children, where it increased from 0.6% to 2.8% from 201 5 to 2022. CONCLUSION: Psychotropic medication use is higher among Australian PwCF compared to the general population, with varying prevalence across age and sex groups. This is of interest due to complexities with CF comorbidities and potential medication influences and interactions. Future studies should investigate the reasons for psychotropic use disparities within PwCF with the aim to establish targeted guidelines and optimize outcomes.

Predictors of persistent opioid use in Australian primary care: A retrospective cohort study, 2018-2022.

OBJECTIVE: To examine the predictors of persistent opioid use ('persistence') in people initiating opioids for non-cancer pain in Australian primary care. DESIGN: A retrospective cohort study. SETTING: Australian primary care. SUBJECTS: People prescribed opioid analgesics between 2018-2022, identified through the Population Level Analysis and Reporting (POLAR) database. METHODS: Persistence was defined as receiving opioid prescriptions for at least 90 days with a gap of less than 60 days between subsequent prescriptions. Multivariable logistic regression was used to examine the predictors of persistent opioid use. RESULTS: The sample consisted of 343,023 people initiating opioids for non-cancer pain; of these, 16,527 (4.8%) developed persistent opioid use. Predictors of persistence included older age (≥75 vs 15-44 years: Adjusted odds ratio: 1.67, 95% CI: 1.58-1.78), concessional beneficiary status (1.78, 1.71-1.86), diagnosis of substance use disorder (1.44, 1.22-1.71) and chronic pain (2.05, 1.85-2.27), initiation of opioid therapy with buprenorphine (1.95, 1.73-2.20) and long-acting opioids (2.07, 1.90-2.25), provision of higher quantity of opioids prescribed at initiation (total OME of ≥ 750mg vs < 100mg: 7.75, 6.89-8.72), provision of repeat/refill opioid prescriptions at initiation (2.94, 2.77-3.12), and prescription of gabapentinoids (1.59, 1.50-1.68), benzodiazepines (1.43, 1.38-1.50) and z-drugs (e.g., zopiclone, zolpidem; 1.61, 1.46-1.78). CONCLUSIONS: These findings add to the limited evidence of individual-level factors associated with persistent opioid use. Further research is needed to understand the clinical outcomes of persistent opioid use in people with these risk factors to support the safe and effective prescribing of opioids.

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.

Longitudinal trends in uptake of hormonal long-acting reversible contraception devices throughout the COVID-19 pandemic: an Australian population-based study.

BACKGROUND: Little is known about the degree to which the COVID-19 pandemic, and associated restrictions and disruptions to health services, impacted the accessibility of hormonal long-acting reversible contraception (LARC) devices within Australia. Here, we explore longitudinal patterns of dispensing of the contraceptive implant and hormonal intrauterine devices (IUDs) within Australia, before and during the COVID-19 pandemic. METHODS: Population-based cohort study; analysis of 10% random sample of national Pharmaceutical Benefits Scheme dispensing data, for females aged 15-49 years dispensed a hormonal LARC device between February 2017 and November 2021. RESULTS: Interrupted time-series analysis demonstrated overall that there were no significant differences in monthly dispensing rates of hormonal LARC following the Australian onset of the pandemic in April 2020, with no subsequent change in the trend. However, when stratified by LARC type, a significant increase was evident during the pandemic period (April 2020-November 2021) in the rate of hormonal IUD dispensing per month (0.20 per 10 000 95% CI 0.01 to 0.38)), compared with a decrease for the implant (-0.08 per 10 000 (95% CI -0.16 to 0.01)). Increases in hormonal IUD dispensing during the pandemic were most pronounced for those aged 20-24 years, new users, those without a Commonwealth concession card, and in the State of Victoria. CONCLUSIONS: Within Australia in the defined pandemic period, access to hormonal LARC devices was not negatively impacted. Rather a significant increase in dispensing of hormonal IUDs was evident.

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.

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, the annual chronic management cost per person 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 (with follow-up data until June 2018 [n = 34,471]). Then extrapolated the data from from Victoria to the whole Australian population aged between 30 years and 99 years to project the total healthcare costs following IS (combination of acute event and chronic management cost) over a 20-year period (2019-2038) using a dynamic multistate life table 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 2 decades on the Australian healthcare system. Our estimated and projected cost burden following IS provides important information for decision making in relation to IS.

Effect of Oral Bisphosphonate Drug Holiday on Mortality Following Hip Fracture.

CONTEXT: Current clinical guidelines recommend a drug holiday after extended use of oral bisphosphonates. However, no studies have investigated the effect of drug holidays before hip fractures on postfracture mortality. OBJECTIVE: This work aimed to investigate the effect of a drug holiday on postfracture mortality in patients with extended use of oral bisphosphonates. METHODS: This retrospective, population-based cohort study took place among all patients with hip fractures in Victoria, Australia, from 2014 to 2018. Patients were adherent to oral alendronate or risedronate for 5 years or more prior to hip fracture. Group-based trajectory modeling categorized patients into different bisphosphonate usage after 5-year good adherence. The main outcome measure was postfracture mortality. RESULTS: We identified 365 patients with good adherence (medication possession ratio ≥80%) to oral alendronate/risedronate for 5 years or more. Most patients (69%) continued to use oral bisphosphonates until admission for hip fracture; 17% had discontinued for 1 year and 14% had discontinued for 2 years. Postfracture mortality was higher in patients who had discontinued risedronate for 1 year (hazard ratio [HR] 2.37; 95% CI, 1.24-4.53) and 2 years (HR 3.08; 95% CI, 1.48-6.41) prior to hip fracture. No increase or decrease in postfracture mortality was observed in patients who had discontinued alendronate for 1 year (HR 0.59; 95% CI, 0.29-1.18) or 2 years (HR 1.05; 95% CI, 0.57-1.93) prior to hip fracture. CONCLUSION: Postfracture mortality is higher in people who discontinue risedronate, but not alendronate, for 1 or 2 years after being adherent to treatment for at least 5 years. The type of bisphosphonate may be a factor to consider when planning drug holidays.

The association between sodium glucose cotransporter-2 inhibitors vs dipeptidyl peptidase-4 inhibitors and renal outcomes in people discharged from hospital with type 2 diabetes: A population-based cohort study.

BACKGROUND: We investigated the association between post-hospital discharge use of sodium glucose cotransporter-2 inhibitors (SGLT-2is) compared to dipeptidyl peptidase-4 inhibitors (DPP-4is) and the incidence of hospitalization for acute renal failure (ARF) and chronic kidney disease (CKD) in people with type 2 diabetes. METHODS: We conducted a retrospective cohort study using linked hospital and prescription data. Our cohort included people aged ≥30 years with type 2 diabetes discharged from a hospital in Victoria, Australia, from December 2013 to June 2018. We compared new users of SGLT-2is with new users of DPP-4is following discharge. People were followed from first dispensing of a SGLT-2i or DPP-4i to a subsequent hospital admission for ARF or CKD. We used competing risk models with inverse probability of treatment weighting (IPTW) to estimate subhazard ratios. RESULTS: In total, 9620 people initiated SGLT-2is and 9962 initiated DPP-4is. The incidence rate of ARF was 12.3 per 1000 person-years (median years of follow-up [interquartile range [IQR] 1.4 [0.7-2.2]) among SGLT-2i initiators and 18.9 per 1000 person-years (median years of follow-up [IQR] 1.7 [0.8-2.6]) among DPP-4i initiators (adjusted subhazard ratio with IPTW 0.78; 95% confidence interval [CI] 0.70-0.86). The incidence rate of CKD was 6.0 per 1000 person-years (median years of follow-up [IQR] 1.4 [0.7-2.2]) among SGLT-2i initiators and 8.9 per 1000 person-years (median years of follow-up [IQR] 1.7 [0.8-2.6]) among DPP-4i initiators (adjusted subhazard ratio with IPTW 0.83; 95% CI 0.73-0.94). CONCLUSIONS: Real-world data support using SGLT-2is over DPP-4is for preventing acute and chronic renal events in people with type 2 diabetes.

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.

The impact of frailty on initiation, continuation and discontinuation of secondary prevention medications following myocardial infarction.

AIM: To evaluate the association between frailty and initiating, continuing, or discontinuing secondary prevention medications following myocardial infarction (MI). METHODS: We conducted a cohort study using linked health data, including all adults aged ≥65 years who discharged from hospital following MI from January 2013 to April 2018 in Victoria, Australia (N = 29,771). The Hospital Frailty Risk Score (HFRS) was used to assess frailty. Logistic regression was used to investigate associations of frailty with initiation, continuation, and discontinuation of secondary prevention medications (P2Y12 inhibitor antiplatelets, beta-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and lipid-lowering therapies) in the 90 days from discharge post-MI, by HFRS, adjusted for age, sex, and Charlson Comorbidity Index. RESULTS: Increasing frailty was associated with lower probability of initiating and continuing P2Y12 inhibitors, RAAS inhibitors, and lipid-lowering therapies, but not beta-blockers. At at an HFRS of 0, the predicted probabiliy of having all four medications initiated or continued was 0.59 (95 %CI 0.57-0.62) for STEMI and 0.35 (0.34-0.36) for non-STEMI, compared to 0.38 (0.33-0.42) and 0.16 (0.14-0.18) at an HFRS of 15. Increasing frailty was associated with higher probability of discontinuing these medications post-MI. The predicted probability of discontinuing at least one secondary prevention medication post-MI at an HFRS of 0 was 0.10 (0.08-0.11) for STEMI and 0.14 (0.13-0.15) for non-STEMI, compared to 0.27 (0.22-0.32) and 0.34 (0.32-0.36) at an HFRS of 15. CONCLUSION: People with higher levels of frailty were managed more conservatively following MI than people with lower levels of frailty. Whether this conservative treatment is justified warrants further study.

SGLT-2 Inhibitor Use and Cause-Specific Hospitalization Rates: An Outcome-Wide Study to Identify Novel Associations of SGLT-2 Inhibitors.

Sodium-glucose co-transporter 2 inhibitors (SGLT2is) have demonstrated multifaceted pharmacological effects. In addition to type 2 diabetes, they are now indicated for heart failure and chronic kidney disease. This study aimed to identify novel associations between SGLT2i use and health outcomes using real-world data. Using linked data from a nationwide diabetes registry in Australia, we compared hospitalization rates in people living with type 2 diabetes commencing treatment with SGLT2i and dipeptidyl peptidase-4 inhibitor (DPP4i) between December 1, 2013, and June 30, 2019. Cause-specific hospitalizations were categorized across three hierarchies of diagnoses (first, first three, and first four digits of International Classification of Diseases, Tenth Version, Australian Modification codes). Incidence rate ratio (IRR) and 95% confidence interval (95% CI) for each cause-specific hospitalization were estimated using negative binomial regression. In the first hierarchy, hospitalization rates were lower across most diagnosis groups among SGLT2i initiators (n = 99,569) compared with DPP4i initiators (n = 186,353). In the second and third hierarchies, there were lower hospitalization rates relating to infections, anemias, and obstructive airway diseases among SGLT2i initiators compared with DPP4i initiators. These included sepsis (IRR: 0.60, 95% CI: 0.51-0.72) anemia (IRR: 0.55, 95% CI: 0.46-0.66), and chronic obstructive pulmonary diseases (IRR: 0.52, 95% CI: 0.40-0.68), as well as for previously known associations (e.g., heart failure (IRR: 0.63, 95% CI: 0.56-0.70)). SGLT2is have previously uncharacterized associations on a range of important clinical outcomes; validation of these associations requires further study, some of which may suggest novel benefits or new indications for SGLT2is.

The effect of frailty on post-discharge management and outcomes of acute glycaemic crises: Analysis of admissions for hypoglycaemia and hyperglycaemia in Australia.

OBJECTIVE: To describe changes in glucose-lowering drug (GLD) dispensing by frailty status for people with diabetes following admission for hypoglycaemia or hyperglycaemia. METHODS: This study included all people with probable type 2 diabetes in the state of Victoria, Australia, admitted to hospital for hypoglycaemia (n = 2,506 admissions) or hyperglycaemia (n = 1,693) between 1 July 2013 and 29 June 2017. Frailty was defined via the Hospital Frailty Risk Score (HFRS). We examined differences in dispensing of GLDs in the year before and after admission using linear regression models adjusted for age, sex, comorbidities, and socioeconomic status. RESULTS: Dispensing of GLDs decreased following hypoglycaemia admission. Decreased dispensing was strongly associated with frailty status, with a change in mean annual GLD dispensing count of -4.11 (-5.05, -3.17) for an HFRS of 15 vs. -0.99 (-1.47, -0.50) for an HFRS of 0. Changes were greatest for metformin and sulfonylureas. Following hyperglycaemia admission, the mean number of annual GLD dispensings increased, with a smaller increase with increasing frailty: 2.44 (1.32, 3.56) for an HFRS of 0 vs. 1.16 (0.18, 2.14) for an HFRS of 15. CONCLUSIONS: Frailty was associated with more conservative diabetes medication management following hypoglycaemia and hyperglycaemia admissions.

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.

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.

No effect of remoteness on clinical outcomes following myocardial infarction: An analysis of 43,729 myocardial infarctions in Victoria, Australia.

BACKGROUND: Remoteness has been shown to predict poor clinical outcomes following myocardial infarction (MI). This study investigated 1-year clinical outcomes following MI by remoteness in Victoria, Australia. METHODS: We included all admissions for people discharged from hospital following MI between July 2012 and June 2017 (n = 43,729). Remoteness was determined using the Accessibility/Remoteness Index of Australia (ARIA). The relationship between remoteness and major adverse cardiovascular events (MACE) and all-cause mortality over 1-year was evaluated using adjusted Poisson regression, stratified by type STEMI and NSTEMI. RESULTS: For NSTEMI, adjusted rates of MACE were 77.5[95% confidence interval 65.1-92.1] for the most remote area versus 83.4[65.5-106.3] for the least remote area per 1000 person-years. For STEMI, rates of MACE were 28.5[18.3-44.6] for the most versus 33.5[18.9-59.4] for the least remote areas per 1000 person-years. With respect to all-cause mortality, NSTEMI mortality rates were 82.2[67.0-100.9] for the most versus 100.8[75.2-135.1] for the least remote areas per 1000 person-years. For STEMI, mortality rates were 24.7[13.7-44.7] for the most versus 22.3[9.8-50.8] for the least remote per 1000 person-years. CONCLUSIONS: Rates of MACE and all-cause mortality were similar in regardless of degree of remoteness, suggesting that initiatives to increase access to cardiology care in more remote areas succeeded in reducing previous disparities.

Use of secondary prevention medications in metropolitan and non-metropolitan areas: an analysis of 41 925 myocardial infarctions in Australia.

AIMS: People in remote areas may have more difficulty accessing healthcare following myocardial infarction (MI) than people in metropolitan areas. We determined whether remoteness was associated with initial and 12-month use of secondary prevention medications following MI in Victoria, Australia. METHODS AND RESULTS: We included all people alive at least 90 days after discharge following MI between July 2012 and June 2017 in Victoria, Australia (n = 41 925). We investigated dispensing of P2Y12 inhibitors (P2Y12i), statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs), and beta-blockers within 90 days after discharge. We estimated 12-month medication use using proportion of days covered (PDC). Remoteness was determined using the Accessibility/Remoteness Index of Australia (ARIA). Data were analysed using adjusted parametric regression models stratified by ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). There were 10 819 STEMI admissions and 31 106 NSTEMI admissions. Following adjustment across NSTEMI and STEMI, there were no medication classes dispensed in the 90-day post-discharge that differed in a clinically significant way from the least remote (ARIA = 0) to the most remote (ARIA = 4.8) areas. The largest difference for NSTEMI was ACEI/ARB, with 71% (95% confidence interval 70-72%) vs. 80% (76-83%). For STEMI, it was statins with 89% (88-90%) vs. 95% (91-97%). Predicted PDC for STEMI and NSTEMI was not clinically significant across remoteness, with the largest difference in NSTEMI being P2Y12i with 48% (47-50%) vs. 55% (51-59%), and in STEMI, it was ACEI/ARB with 68% (67-69%) vs. 76% (70-80%). CONCLUSION: Remoteness does not appear to be a clinically significant driver for medication use following MI. Possible differences in cardiovascular outcomes in metropolitan and non-metropolitan areas are not likely to be explained by access to secondary prevention medications.

We investigated how where a person lives may affect the use of medications required following a heart attack. Our research used dispensing information and hospital admission information for a population of 41 925 heart attack admissions. Our main findings were as follows: There were no clinically significant differences in initial dispensing or 12-month use of secondary prevention medications with respect to how remote a person may live in Victoria, Australia.Our research suggests that there is equal access to medications with respect to remoteness, and any differences in quality of life or life expectancy following a heart attack are unlikely to be driven by differences in access to medications.

Opioid characteristics and nonopioid interventions associated with successful opioid taper in patients with chronic noncancer pain.

ABSTRACT: Current research indicates that tapering opioids may improve pain and function in patients with chronic noncancer pain. However, gaps in the literature remain regarding the choice of opioid and nonopioid interventions to support a successful taper. This study used an Australian primary care data set to identify a cohort of patients on long-term opioid therapy commencing opioid taper between January 2016 and September 2019. Using logistic regression analysis, we compared key clinical factors associated with differing taper outcomes. Of a total of 3371 patients who commenced taper, 1068 (31.7%) completed taper within 12 months. In the 3 months after commencement of taper, compared with those who did not complete taper, patients who successfully completed opioid taper were less likely to be prescribed buprenorphine (odds ratio [OR] 0.691; 95% CI: 0.530-0.901), fentanyl (OR, 0.429; 95% CI: 0.295-0.622), and long-acting (LA) opioids, including methadone (OR, 0.349; 95% CI: 0.157-0.774), oxycodone-naloxone (OR, 0.521; 95% CI: 0.407-0.669), and LA tapentadol (OR, 0.645; 95% CI: 0.461-0.902), but more likely to be prescribed codeine (OR, 1.308; 95% CI: 1.036-1.652). Compared with those who did not complete taper, patients who successfully tapered were less likely to be prescribed any formulations of oxycodone (short-acting [SA]: OR, 0.533; 95% CI: 0.422-0.672, LA: OR, 0.356; 95% CI: 0.240-0.530) and tramadol (SA: OR, 0.370; 95% CI: 0.218-0.628, LA: OR, 0.317; 95% CI: 0.234-0.428). The type of opioid prescribed in the months after commencement of taper seems to influence the taper outcomes. These findings may inform prospective studies on opioid taper.

COX2 inhibitor use and type 2 diabetes treatment intensification: A registry-based cohort study.

AIM: This study examined the association between cyclooxygenase-2 inhibitor (COX2i) use and diabetes progression in people with type 2 diabetes. METHODS: We conducted a nation-wide cohort study using an Australian diabetes registry linked to medication dispensing data. We assessed time to diabetes treatment intensification among new users of COX2i compared to mild opioids. Inverse probability of treatment-weighted Cox regression models were used to adjust for age, sex, time since diabetes diagnosis, comorbidities, and socio-economic disadvantage. We conducted several sensitivity analyses, including per-protocol analyses and comparing use of any NSAID to mild opioids. RESULTS: There were 8,071 new users of COX2i and 7,623 of mild opioids with 4,168 diabetes treatment intensifications over a median follow-up of 1.6 years. Use of COX2i was associated with decreased risk of treatment intensification when compared to mild opioids (HR 0.91, 95 %CI 0.85-0.96). The results were not significant in the per-protocol analyses. Use of any NSAID was associated with a lower risk of treatment intensification compared to mild opioids (HR 0.90, 95 %CI 0.85-0.96). CONCLUSIONS: Treatment with COX2i may be associated with a modest decreased risk of diabetes treatment intensification compared to mild opioids. Future clinical studies are required to confirm whether COX2 inhibition has clinically significant benefits for glycaemic control.