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.

A causal model for primary prevention of cardiovascular disease: the health economic model for the primary prevention of cardiovascular disease (HEM-PPCVD).

OBJECTIVE: Our objective was to design and develop an open-source model capable of simulating interventions for primary prevention of cardiovascular disease (CVD) that incorporated the cumulative effects of risk factors (e.g., cholesterol-years or blood pressure-years) to enhance health economic modelling in settings where clinical trials are not possible. METHODS: We reviewed the literature to design the model structure by selecting the most important causal risk factors for CVD - low-density lipoprotein-cholesterol (LDL-C), systolic blood pressure (SBP), smoking, diabetes, and lipoprotein (a) (Lp(a)) - and most common CVDs - myocardial infarction and stroke. The epidemiological basis of the model involves the simulation of risk factor trajectories, which are used to modify CVD risk via causal effect estimates derived from Mendelian randomisation. LDL-C, SBP, Lp(a), and smoking all have cumulative impacts on CVD risk, which were incorporated into the health economic model. The data for the model was primarily sourced from the UK Biobank study. We calibrated the model using clinical trial data and validated the model against the observed UK Biobank data. Finally, we performed an example health economic analysis to demonstrate the utility of the model. The model is open source. RESULTS: The model performed well in all validation tests. It was able to produce interpretable and plausible (consistent with expectations of the existing literature) results from an example health economic analysis. CONCLUSIONS: We have constructed an open-source health economic model capable of incorporating the cumulative effect of LDL-C (i.e., cholesterol-years), SBP (SBP-years), Lp(a), and smoking on lifetime CVD risk.

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.

Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis.

AIMS/HYPOTHESIS: Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs. METHODS: We designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained. RESULTS: The numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs. CONCLUSIONS/INTERPRETATION: At current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.

Global trends in the incidence of hospital admissions for diabetes-related foot disease and amputations: a review of national rates in the 21st century.

AIMS/HYPOTHESIS: Diabetic foot disease (DFD) is a leading cause of hospital admissions and amputations. Global trends in diabetes-related amputations have been previously reviewed, but trends in hospital admissions for multiple other DFD conditions have not. This review analysed the published incidence of hospital admissions for DFD conditions (ulceration, infection, peripheral artery disease [PAD], neuropathy) and diabetes-related amputations (minor and major) in nationally representative populations. METHODS: PubMed and Embase were searched for peer-reviewed publications between 1 January 2001 and 5 May 2022 using the terms 'diabetes', 'DFD', 'amputation', 'incidence' and 'nation'. Search results were screened and publications reporting the incidence of hospital admissions for a DFD condition or a diabetes-related amputation among a population representative of a country were included. Key data were extracted from included publications and initial rates, end rates and relative trends over time summarised using medians (ranges). RESULTS: Of 2527 publications identified, 71 met the eligibility criteria, reporting admission rates for 27 countries (93% high-income countries). Of the included publications, 14 reported on DFD and 66 reported on amputation (nine reported both). The median (range) incidence of admissions per 1000 person-years with diabetes was 16.3 (8.4-36.6) for DFD conditions (5.1 [1.3-7.6] for ulceration; 5.6 [3.8-9.0] for infection; 2.5 [0.9-3.1] for PAD) and 3.1 (1.4-10.3) for amputations (1.2 [0.2-4.2] for major; 1.6 [0.3-4.3] for minor). The proportions of the reported populations with decreasing, stable and increasing admission trends were 80%, 20% and 0% for DFD conditions (50%, 0% and 50% for ulceration; 50%, 17% and 33% for infection; 67%, 0% and 33% for PAD) and 80%, 7% and 13% for amputations (80%, 17% and 3% for major; 52%, 15% and 33% for minor), respectively. CONCLUSIONS/INTERPRETATION: These findings suggest that hospital admission rates for all DFD conditions are considerably higher than those for amputations alone and, thus, the more common practice of reporting admission rates only for amputations may substantially underestimate the burden of DFD. While major amputation rates appear to be largely decreasing, this is not the case for hospital admissions for DFD conditions or minor amputation in many populations. However, true global conclusions are limited because of a lack of consistent definitions used to identify admission rates for DFD conditions and amputations, alongside a lack of data from low- and middle-income countries. We recommend that these areas are addressed in future studies. REGISTRATION: This review was registered in the Open Science Framework database ( https://doi.org/10.17605/OSF.IO/4TZFJ ).

Trends in the Incidence of End-Stage Kidney Disease in Type 1 and Type 2 Diabetes in Australia, 2010-2019.

RATIONALE & OBJECTIVE: Trends in end-stage kidney disease (ESKD) among people with diabetes may inform clinical management and public health strategies. We estimated trends in the incidence of ESKD among people with type 1 and type 2 diabetes in Australia from 2010-2019 and evaluated their associated factors. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 71,700 people with type 1 and 1,112,690 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS). We estimated the incidence of kidney replacement therapy (KRT) via linkage to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and the incidence of KRT or death from ESKD by linking the NDSS to the ANZDATA and the National Death Index for Australia. PREDICTORS: Calendar time, sex, age, and duration of diabetes. OUTCOME: Incidence of KRT and KRT or death from ESKD. ANALYTICAL APPROACH: Incidence of ESKD, trends over time, and associations with factors related to these trends were modeled using Poisson regression stratified by diabetes type and sex. RESULTS: The median duration of diabetes increased from 15.3 to 16.8 years in type 1 diabetes, and from 7.6 to 10.2 years in type 2 diabetes between 2010 and 2019. The incidence of KRT and KRT or death from ESKD did not significantly change over this time interval among people with type 1 diabetes. Conversely, the age-adjusted incidence of KRT and KRT or death from ESKD increased among males with type 2 diabetes (annual percent changes [APCs]: 2.52% [95% CI, 1.54 to -3.52] and 1.27% [95% CI, 0.53 2.03], respectively), with no significant change among females (0.67% [95% CI, -0.68 to 2.04] and 0.07% [95% CI, -0.81 to 0.96], respectively). After further adjustment for duration of diabetes, the incidence of ESKD fell between 2010 and 2019, with APCs of-0.09% (95% CI, -1.06 to 0.89) and-2.63% (95% CI, -3.96 to-1.27) for KRT and-0.97% (95% CI, -1.71 to-0.23) and-2.75% (95% CI, -3.62 to-1.87) for KRT or death from ESKD among males and females, respectively. LIMITATIONS: NDSS only captures 80%-90% of people with diabetes; lack of clinical covariates limits understanding of trends. CONCLUSIONS: While the age-adjusted incidence of ESKD increased for males and was stable for females over the last decade, after adjusting for increases in duration of diabetes the risk of developing ESKD has decreased for both males and females. PLAIN-LANGUAGE SUMMARY: Previous studies showed an increase in new cases of kidney failure among people with type 2 diabetes, but more recent data have not been available. Here, we report trends in the rate of kidney failure for people with type 2 diabetes from 2010 to 2019 and showed that while more people with type 2 diabetes are developing kidney failure, accounting for the fact that they are also surviving longer (and therefore have a higher chance of kidney failure) the growth in this population is not caused by a higher risk of kidney failure. Nevertheless, more people are getting kidney failure than before, which will impact health care systems for years to come.

Targeting Diabetes Prevention to More Disadvantaged Groups Improves Cost-Effectiveness: Implications of Inequality in Type 2 Diabetes From Theoretical Interventions.

OBJECTIVES: To determine the effect of socioeconomic status on efficacy and cost thresholds at which theoretical diabetes prevention policies become cost-effective. METHODS: We designed a life table model using real-world data that captured diabetes incidence and all-cause mortality in people with and without diabetes by socioeconomic disadvantage. The model used data from the Australian diabetes registry for people with diabetes and the Australian Institute of Health and Welfare for the general population. We simulated theoretical diabetes prevention policies and estimated the threshold at which they would be cost-effective and cost saving, overall, and by socioeconomic disadvantage, from the public healthcare perspective. RESULTS: From 2020 to 2029, 653 980 people were projected to develop type 2 diabetes, 101 583 in the least disadvantaged quintile and 166 744 in the most. Theoretical diabetes prevention policies that reduce diabetes incidence by 10% and 25% would be cost-effective in the total population at a maximum per person cost of Australian dollar (AU$) 74 (95% uncertainty interval: 53-99) and AU$187 (133-249) and cost saving at AU$26 (20-33) and AU$65 (50-84). Theoretical diabetes prevention policies remained cost-effective at a higher cost in the most versus least disadvantaged quintile (eg, a policy that reduces type 2 diabetes incidence by 25% would be cost-effective at AU$238 [169-319] per person in the most disadvantaged quintile vs AU$144 [103-192] in the least). CONCLUSIONS: Policies targeted at more disadvantaged populations will likely be cost-effective at higher costs and lower efficacy compared to untargeted policies. Future health economic models should incorporate measures of socioeconomic disadvantage to improve targeting of interventions.

Mortality trends in type 1 diabetes: a multicountry analysis of six population-based cohorts.

AIMS/HYPOTHESIS: Mortality has declined in people with type 1 diabetes in recent decades. We examined how the pattern of decline differs by country, age and sex, and how mortality trends in type 1 diabetes relate to trends in general population mortality. METHODS: We assembled aggregate data on all-cause mortality during the period 2000-2016 in people with type 1 diabetes aged 0-79 years from Australia, Denmark, Latvia, Scotland, Spain (Catalonia) and the USA (Kaiser Permanente Northwest). Data were obtained from administrative sources, health insurance records and registries. All-cause mortality rates in people with type 1 diabetes, and standardised mortality ratios (SMRs) comparing type 1 diabetes with the non-diabetic population, were modelled using Poisson regression, with age and calendar time as quantitative variables, describing the effects using restricted cubic splines with six knots for age and calendar time. Mortality rates were standardised to the age distribution of the aggregate population with type 1 diabetes. RESULTS: All six data sources showed a decline in age- and sex-standardised all-cause mortality rates in people with type 1 diabetes from 2000 to 2016 (or a subset thereof), with annual changes in mortality rates ranging from -2.1% (95% CI -2.8%, -1.3%) to -5.8% (95% CI -6.5%, -5.1%). All-cause mortality was higher for male individuals and for older individuals, but the rate of decline in mortality was generally unaffected by sex or age. SMR was higher in female individuals than male individuals, and appeared to peak at ages 40-70 years. SMR declined over time in Denmark, Scotland and Spain, while remaining stable in the other three data sources. CONCLUSIONS/INTERPRETATION: All-cause mortality in people with type 1 diabetes has declined in recent years in most included populations, but improvements in mortality relative to the non-diabetic population are less consistent.

Persistent disparities in diabetes medication receipt by socio-economic disadvantage in Australia.

BACKGROUND: It is unknown how use of newer glucose-lowering drugs (GLDs) has changed in Australia following the publication of clinical trials demonstrating definitive clinical advantages for glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT2is), and whether this varies by socio-economic disadvantage. METHODS: We included 1,064,645 people with type 2 diabetes registered on the National Diabetes Services Scheme. This cohort was linked to the Pharmaceutical Benefits Scheme database to evaluate trends in diabetes medication receipt and variation by socio-economic disadvantage between 2013 and 2019. RESULTS: The proportion of people with type 2 diabetes receiving ≥3 GLDs concurrently increased from 12% in 2013 to 25% in 2019. By 2019, 6% of people with diabetes were receiving a GLP-1 RA and 21% an SGLT2i. Disparities in receipt of GLP-1 RAs and SGLT2is by socio-economic disadvantage decreased over time (ORs for most vs. least disadvantaged quintile were 0.80 [0.77-0.85] and 0.87 [0.82-0.94] in 2014 and 0.95 [0.92-0.98] and 1.07 [1.05-1.09] in 2019 for GLP-1 RAs and SGLT2is, respectively). However, people in more disadvantaged areas were more likely to receive multiple GLDs. After stratifying by number of concurrent GLDs received, people in more disadvantaged areas were less likely to receive GLP-1 RAs and SGLT2is in 2019 (ORs for most vs. least disadvantaged: 0.81 [0.78-0.84] and 0.90 [0.87-0.93] for people receiving ≥3 GLDs, respectively). CONCLUSIONS: After controlling for intensity of glucose-lowering therapy, people in more disadvantaged areas were less likely to receive cardioprotective GLDs, although disparities decreased over time.

Excess all-cause and cause-specific mortality for people with diabetes and end-stage kidney disease.

AIMS: Excess mortality is high in the setting of diabetes and end-stage kidney disease (ESKD), but the effects of ESKD beyond diabetes itself remains incompletely understood. We examined excess mortality in people with diabetes with versus without ESKD, and variation by age, sex and diabetes type. METHODS: This study included 63,599 people with type 1 (aged 20-69 years; 56% men) and 1,172,160 people with type 2 diabetes (aged 30+ years; 54% men), from the Australian National Diabetes Services Scheme. Initiation of renal replacement therapy and mortality outcomes were obtained via linkage to the Australia and New Zealand Dialysis and Transplant Registry and the National Death Index, respectively. Excess mortality was measured by calculating the mortality rate ratio (MRR) for people with versus without ESKD via indirect standardisation. RESULTS: A total of 9027 people developed ESKD during 8,601,522 person-years of follow-up. Among people with type 1 diabetes, the MRR was 34.9 (95%CI: 16.6-73.1) in men and 41.5 (20.8-83.1) in women aged 20-29 years and was 5.6 (4.5-7.0) and 7.4 (5.5-10.1) in men and women aged 60-69 years, respectively. In type 2 diabetes, MRRs were 16.6 (8.6-31.8) and 35.8 (17.0-75.2) at age 30-39 years and were 2.8 (2.6-3.1) and 3.6 (3.2-4.1) at age 80+ years in men and women, respectively. Excess cause-specific mortality was highest for peripheral artery disease, cardiac arrest, and infections, and lowest for cancer. CONCLUSIONS: Among people with diabetes, excess mortality in ESKD is much higher at younger ages and is higher for women compared with men.

Changes in excess mortality among adults with diabetes-related end-stage kidney disease: a comparison between the USA and Australia.

BACKGROUND: The number of people with diabetes-related end-stage kidney disease (ESKD-DM) has doubled in the last two decades. We examined changes in excess mortality for people with ESKD-DM in the USA and Australia. METHODS: In this retrospective cohort study, we included adults (ages 20-84 years) receiving renal replacement therapy (RRT) for ESKD-DM in the USA (n = 1 178 860 from the United States Renal Data System, 2002-17) and Australia (n = 10 381 from the Australia and New Zealand Dialysis and Transplant Registry, 2002-13). ESKD-DM was defined as those with diagnosed diabetes at time of RRT initiation and mortality status was captured from national death registries. Annual standardized mortality ratios (SMR) were stratified by treatment modality, and age, sex and race (USA only). Trends were assessed using join point regression and annual percent change (APC) was reported. RESULTS: Overall, in the dialysis population SMR decreased from 2006 to 2014 in the USA (from 12.0 to 10.1; APC -2.1) and from 2002 to 2013 in Australia (from 12.0 to 9.4; APC -3.4). In the transplant population, SMR decreased from 6.2 to 4.0 from 2002 to 2013 in the USA, and did not significantly change from 2002 to 2013 in Australia. By subgroup, excess mortality was higher in women (versus men), younger (versus older) adults, dialysis (versus transplant) patients, and in Asian or Pacific Islanders and American Indian or Alaskan Natives (AI/AN) (versus Whites and Blacks). SMRs declined similarly across all subgroups excluding AI/AN (USA) and transplant patients (Australia), where relative declines were smaller. CONCLUSIONS: Excess mortality for people with ESKD-DM treated with dialysis or transplant has decreased in the USA and Australia, but progress has stalled from ∼2013 in the USA. Nevertheless, mortality remains more than nine times higher in ESKD-DM versus the general population, with important variations by subgroups. Given the increasing burden of diabetes in the population, a focus on reducing excess mortality risk in the ESKD-DM population is needed.

The association of socioeconomic disadvantage and remoteness with receipt of type 2 diabetes medications in Australia: a nationwide registry study.

AIMS/HYPOTHESIS: In recent years, several new medications for the treatment of type 2 diabetes have been released and some evidence indicates sociodemographic disparity in their utilisation. We sought to investigate sociodemographic disparities in receipt of diabetes medications across Australia. METHODS: This study included 1,203,317 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS) followed from 2007 to 2015. The NDSS was linked to the Australian pharmaceutical claims database. We investigated trends in diabetes medication dispensing and variation in dispensing by sociodemographic strata. RESULTS: Compared with individuals in the least disadvantaged areas, those in the most disadvantaged quintile were less likely to receive dipeptidyl peptidase-4 inhibitors (DPP4is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) in the first year of availability (OR [95% CI] for most vs least disadvantaged: 0.78 [0.75, 0.82], 0.65 [0.60, 0.71] and 0.89 [0.84, 0.95], respectively). These disparities dissipated over time for DPP4is and SGLT2is but remained significant for GLP-1RAs. The OR (95% CI) of receiving DPP4is, GLP-1RAs and SGLT2is in the first year of availability for people in remote areas vs major cities was 0.46 (0.39, 0.54), 0.46 (0.35, 0.61) and 0.71 (0.59, 0.84), respectively. These disparities remained significant through to 2015. CONCLUSIONS/INTERPRETATION: People with diabetes in more disadvantaged areas are less likely to receive newer diabetes medications, although this effect decreased over time. However, there are considerable and persistent differences in receipt of newer diabetes medications between major cities and remote areas of Australia. Graphical abstract.

Health economics of detection and treatment of children with familial hypercholesterolemia: to screen or not to screen is no longer the question.

PURPOSE OF REVIEW: Heterozygous familial hypercholesterolemia (HeFH) is one of the most common monogenic disorders and is safely treatable with lipid-lowering medication. However, most individuals with HeFH remain untreated and undetected, especially in paediatric populations where the potential for long-term therapeutic benefit is higher. Here, we review the recent literature on health economic outcomes for the detection and management of FH in children. RECENT FINDINGS: A targeted literature review identified eight studies evaluating detection and management strategies for paediatric FH populations in the last 25 years. Most studies conducted modelled cost-effectiveness analyses to understand the long-term impact of these strategies on health outcomes and the financial impact on the healthcare system. All studies reported that detection and management of HeFH in paediatric populations was cost-effective, regardless of the age of the children. However, cost-effectiveness varied depending on the method of case ascertainment - targeted screening was generally cheaper overall, but less effective, than whole-of-population screening, although both methods were generally cost-effective. SUMMARY: Detection and management of HeFH in paediatric populations is a cost-effective way to significantly lower the burden of disease later in life for these individuals. These strategies should be implemented across healthcare systems.

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.

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.

Lipid-Lowering Strategies for Primary Prevention of Coronary Heart Disease in the UK: A Cost-Effectiveness Analysis.

AIM: We aimed to assess the cost effectiveness of four different lipid-lowering strategies for primary prevention of coronary heart disease initiated at ages 30, 40, 50, and 60 years from the UK National Health Service perspective. METHODS: We developed a microsimulation model comparing the initiation of a lipid-lowering strategy to current standard of care (control). We included 458,692 participants of the UK Biobank study. The four lipid-lowering strategies were: (1) low/moderate-intensity statins; (2) high-intensity statins; (3) low/moderate-intensity statins and ezetimibe; and (4) inclisiran. The main outcome was the incremental cost-effectiveness ratio for each lipid-lowering strategy compared to the control, with 3.5% annual discounting using 2021 GBP (£); incremental cost-effectiveness ratios were compared to the UK willingness-to-pay threshold of £20,000-£30,000 per quality-adjusted life-year. RESULTS: The most effective intervention, low/moderate-intensity statins and ezetimibe, was projected to lead to a gain in quality-adjusted life-years of 0.067 per person initiated at 30 and 0.026 at age 60 years. Initiating therapy at 40 years of age was the most cost effective for all lipid-lowering strategies, with incremental cost-effectiveness ratios of £2553 (95% uncertainty interval: 1270, 3969), £4511 (3138, 6401), £11,107 (8655, 14,508), and £1,406,296 (1,121,775, 1,796,281) per quality-adjusted life-year gained for strategies 1-4, respectively. Incremental cost-effectiveness ratios were lower for male individuals (vs female individuals) and for people with higher (vs lower) low-density lipoprotein-cholesterol. For example, low/moderate-intensity statin use initiated from age 40 years had an incremental cost-effectiveness ratio of £5891 (3822, 9348), £2174 (772, 4216), and was dominant (i.e. cost saving; -2,760, 350) in female individuals with a low-density lipoprotein-cholesterol of ≥ 3.0, ≥ 4.0 and ≥ 5.0 mmol/L, respectively. Inclisiran was not cost effective in any sub-group at its current price. CONCLUSIONS: Low-density lipoprotein-cholesterol lowering from early ages is a more cost-effective strategy than late intervention and cost effectiveness increased with the increasing lifetime risk of coronary heart disease.

Excess Risk of Injury in Individuals With Type 1 or Type 2 Diabetes Compared With the General Population.

OBJECTIVE: To estimate the relative risk (RR) and excess hospitalization rate for injury in individuals with diabetes compared with the general population. RESEARCH DESIGN AND METHODS: Data were obtained from the Australian National Diabetes Services Scheme, hospitalization data sets, the Australian Pharmaceutical Benefits Scheme, the National Death Index, and the census spanning from 2011 to 2017. Hospitalizations for injury were coded as head and neck, lower-extremity, upper-extremity, or abdominal and thoracic injury; burns; or other injury. Poisson regression was used to estimate the age- and sex-adjusted RR of hospitalization for injury. RESULTS: The total number of hospitalizations for any injury was 117,705 in people with diabetes and 3,463,173 in the general population. Compared with that in the general population, an elevated adjusted risk of admission was observed for any injury (RR 1.22; 95% CI 1.21, 1.22), head and neck (1.28; 1.26, 1.30), lower extremity (1.24; 1.23, 1.26), abdominal and thoracic (1.29; 1.27, 1.30), upper extremity (1.03; 1.02, 1.05), burns (1.52; 1.44, 1.61), and other injury (1.37; 1.33, 1.40). The adjusted RR of any injury was 1.62 (1.58, 1.66) in individuals with type 1 diabetes, 1.65 (1.63, 1.66) in those with type 2 diabetes who were taking insulin, and 1.07 (1.06, 1.08) in individuals with type 2 diabetes not using insulin. Falls were the primary cause of injury in individuals with diabetes. CONCLUSIONS: Individuals with diabetes, especially those using insulin, had a higher risk of hospitalization for injury compared with the general population.

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.