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Background Aboriginal Australians are known to suffer high levels of acquired brain injury (stroke and traumatic brain injury) yet experience significant barriers in accessing rehabilitation services. The aim of the Healing Right Way trial is to evaluate a culturally secure intervention for Aboriginal people with newly acquired brain injury to improve their rehabilitation experience and quality of life. Following publication of the trial protocol, this paper outlines the statistical analysis plan prior to locking the database. Methods The trial involves a stepped wedge design with four steps over 3 years. Participants were 108 adult Aboriginal Australians admitted to one of eight hospitals (four rural, four urban) in Western Australia within 6 weeks of onset of a new stroke or traumatic brain injury who consented to follow-up for 26 weeks. All hospital sites started in a control phase, with the intervention assigned to pairs of sites (one metropolitan, one rural) every 26 weeks until all sites received the intervention. The two-component intervention involves training in culturally safe care for hospital sites and enhanced support provided to participants by Aboriginal Brain Injury Coordinators during their hospital stay and after discharge. The primary outcome is quality of life as measured by the Euro QOL–5D-3L VAS. A mixed effects linear regression model will be used to assess the between-group difference at 26 weeks post-injury. The model will control for injury type and severity, age at recruitment and time since commencement of the trial, as fixed effects. Recruitment site and participant will be included as random effects. Secondary outcomes include measurements of function, independence, anxiety and depression, carer strain, allied health occasions of service received and hospital compliance with minimum processes of care based on clinical guidelines and best practice models of care. Discussion The trial will provide the first data surrounding the effectiven

BACKGROUND: Aboriginal Australians are known to suffer high levels of acquired brain injury (stroke and traumatic brain injury) yet experience significant barriers in accessing rehabilitation services. The aim of the Healing Right Way trial is to evaluate a culturally secure intervention for Aboriginal people with newly acquired brain injury to improve their rehabilitation experience and quality of life. Following publication of the trial protocol, this paper outlines the statistical analysis plan prior to locking the database. METHODS: The trial involves a stepped wedge design with four steps over 3 years. Participants were 108 adult Aboriginal Australians admitted to one of eight hospitals (four rural, four urban) in Western Australia within 6 weeks of onset of a new stroke or traumatic brain injury who consented to follow-up for 26 weeks. All hospital sites started in a control phase, with the intervention assigned to pairs of sites (one metropolitan, one rural) every 26 weeks until all sites received the intervention. The two-component intervention involves training in culturally safe care for hospital sites and enhanced support provided to participants by Aboriginal Brain Injury Coordinators during their hospital stay and after discharge. The primary outcome is quality of life as measured by the Euro QOL-5D-3L VAS. A mixed effects linear regression model will be used to assess the between-group difference at 26 weeks post-injury. The model will control for injury type and severity, age at recruitment and time since commencement of the trial, as fixed effects. Recruitment site and participant will be included as random effects. Secondary outcomes include measurements of function, independence, anxiety and depression, carer strain, allied health occasions of service received and hospital compliance with minimum processes of care based on clinical guidelines and best practice models of care. DISCUSSION: The trial will provide the first data surrounding the effect

Background And Aims: An estimated 370 million indigenous people live across 90 nations worldwide. Despite the known substantial health and socioeconomic disadvantage experienced by Indigenous populations of developed nations, comparative data on the incidence of stroke in these populations are sparse. We aim to undertake a systematic review of the incidence of stroke in Indigenous populations of developed nations, with comparisons between Indigenous and non-Indigenous populations, and between different Indigenous populations. Method(s): Using PubMed, EMBASE and CINAHL-Plus databases, we will examine whole-of-population incidence studies of stroke in Indigenous populations of developed nations published 2000-2019, without language restriction. Non-peer-reviewed sources, studies having <10 Indigenous people, or with insufficient data to determine incidence, will be excluded. Two reviewers will independently validate the search strategies, screen titles and abstracts, and record reasons for rejection. Relevant articles will undergo full-text screening, using the Newcastle-Ottawa Scale to assess risk of bias, and standard data extracted for all studies included. Result(s): Primary outcomes include crude, age-specific and/or age-standardised incidence of stroke. Secondary outcomes include stroke attack rates, incidence rate ratio and case-fatality. Results will be synthesized in figures and tables, describing data sources, populations, methodology, and findings. Due to anticipated heterogeneity of data, results will be reported narratively. Conclusion(s): We will report the first systematic review undertaken to explicitly assess inequities in stroke incidence in Indigenous populations of developed nations. We predict that stroke incidence in Indigenous populations are substantially greater than in non-Indigenous populations, with significant variation in Indigenous rates and rate-ratios between different countries.

Background: Most estimates of stroke incidence among Aboriginal and Torres Strait Islander (hereinafter respectfully referred to as Aboriginal) Australians include limited case numbers and are generally confined to single regions. Aim(s): To measure age-standardised stroke incidence in Aboriginal and non-Aboriginal Australians in Western Australia (WA), South Australia (SA) and the Northern Territory (NT) combined. Method(s): We used whole-population multi-jurisdictional person-linked data from hospital and death datasets to identify stroke admissions and stroke-related deaths (2001-2015). We utilised hospital, emergency department and death datasets to identify Aboriginal people. We identified incident (firstever) strokes in patients aged 20-84 during the study period (2012-2015), using a 10-year lookback period to exclude previous stroke events. Incidence rates for the Aboriginal and non-Aboriginal population per 100,000/year were estimated, age-standardised to the world population aged 20-84. Result(s): We identified 17,986 incident strokes (32.2% fatal) between 2012-2015. Of these, 752 (4.2%) occurred in Aboriginal people (23.1% fatal). Median age at onset (55 years) in Aboriginal people was 16 years younger than non-Aboriginal people (p<0.001). In those aged 20-84 years, the age-standardised stroke incidence was 2.9-fold greater in the Aboriginal population (206/100,000) than the non- Aboriginal population (70/100,000). Disparities were particularly apparent at younger ages (20-54 years), where the age-standardised stroke incidence was 4.4-fold greater in the Aboriginal population (93/100,000) than the non-Aboriginal population (21/100,000). Conclusion(s): In the largest multi-jurisdictional person-linked dataset to date we found significant disparities in stroke incidence between Aboriginal and non-Aboriginal populations, particularly at younger ages. These results will be used to inform region-specific, culturally safe interventions.

BACKGROUND: The World Health Organisation previously recommended routine screening in school-aged children in countries with a high prevalence of rheumatic heart disease (RHD); however, it is unclear if screening-detected (latent) valve disease will inevitably evolve to a pathological lesion. Understanding the natural history of latent RHD is essential prior to recommendation of screening in endemic areas. Studies documenting the progression of latent RHD have had contrasting conclusions about the pathogenicity of latent valvular lesions. This review provides estimates of rates of progression of latent RHD. METHODS AND FINDINGS: In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, Global Index Medicus, Africa Wide, Cochrane Database of Systematic Reviews and Global Health Database for studies published before April 30, 2019. Study data were extracted from all studies which reported follow-up data on progression of latent valve lesions. Studies with control cohorts were used to calculate comparative prevalence ratios. This study is registered with PROSPERO, number CRD42019119427. We identified 12 studies reporting follow-up data on latent RHD for 950 people in 9 countries. The estimated pooled prevalence rate for progression per year of latent RHD was 5%/year (95% CI 2-8). Eight studies reported on the progression of borderline latent RHD with an estimated pooled prevalence of 2%/year (95% CI 0-4). Three studies included control groups. There was a significant increase in the risk of progression of valvular disease in the latent group compared with controls (RR = 3.57 (95%CI = 1.65-7.70, P = 0.001). The overall risk of bias was low. Given most studies included penicillin administration we were unable to document the natural history of latent RHD. Furthermore, we were unable to perform a sensitivity analysis to determine the effect of administering penicillin prophylaxis on progression of valve disease given prescription of penicillin was not stan

OBJECTIVES: We aimed to compare the incidence, subtypes and aetiology of stroke, and in-hospital death due to stroke, between Aboriginal and non-Aboriginal people in Central Australia, a remote region of Australia where a high proportion Aboriginal people reside (40% of the population). We hypothesised that the rates of stroke, particularly in younger adults, would be greater in the Aboriginal population, compared with the non-Aboriginal population; we aimed to elucidate causes for any identified disparities. DESIGN: A retrospective population-based study of patients hospitalised with stroke within a defined region from 1 January 2011 to 31 December 2014. SETTING: Alice Springs Hospital, the only neuroimaging-capable acute hospital in Central Australia, serving a network of 50 healthcare facilities covering 672 000 km2. PARTICIPANTS: 161 residents (63.4% Aboriginal) of the catchment area admitted to hospital with stroke. PRIMARY AND SECONDARY OUTCOME MEASURES: Rates of first-ever stroke, overall (all events) stroke and in-hospital death. RESULTS: Of 121 residents with first-ever stroke, 61% identified as Aboriginal. Median onset-age (54 years) was 17 years younger in Aboriginal patients (p<0.001), and age-standardised stroke incidence was threefold that of non-Aboriginal patients (153 vs 51 per 100 000, incidence rate ratio 3.0, 95% CI 2 to 4). The rate ratios for the overall rate of stroke (first-ever and recurrent) were similar. In Aboriginal patients aged <55 years, the incidence of ischaemic stroke was 14-fold greater (95% CI 4 to 45), and intracerebral haemorrhage 19-fold greater (95% CI 3 to 142) than in non-Aboriginal patients. Crude prevalence of diabetes mellitus (70.3% vs 34.0%, p<0.001) and hypercholesterolaemia (68.9% vs 51.1%, p=0.049) was greater, and age-standardised in-hospital deaths were fivefold greater (35 vs 7 per 100 000, 95% CI 2 to 11) in Aboriginal patients than in non-Aboriginal patients. CONCLUSIONS: Stroke incidence (both subtypes) and in

Background: Aboriginal and Torres Strait Islander (Indigenous) Australians have greater rates of cardiovascular disease-related morbidity and mortality, but there are no prospective population-based studies of stroke incidence in this population. We present the first prospective population-based pilot study of stroke incidence and outcomes in Indigenous Australians. Method(s): All suspected strokes in patients from pre-specified postcodes were prospectively assessed across seven hospitals in South Australia and the Northern Territory from 01/10/2015 to 31/12/2015, with three-month follow-up of all cases. Clinical and radiological data were examined to determine stroke type. Result(s): Of 123 residents with first-ever stroke, 8% identified as Indigenous. The median age of incident stroke was 44 (interquartile range [IQR] 33, 55), 29 years younger than non-Indigenous Australians (73, IQR 62, 84, p < 0.001). Age-standardised stroke incidence was over 3-fold greater in Indigenous than non-Indigenous people (104 vs 33 per 100,000, p < 0.001). In those aged <55 years, stroke incidence was nearly 7-fold greater in Indigenous than non-Indigenous people (95% confidence interval 3-16, p < 0.001). Whilst all traditional stroke risk factors appeared more prevalent in Indigenous Australians, none reached statistical significance. Conclusion(s): There are marked disparities in stroke incidence and age of onset between Indigenous and non-Indigenous Australians. Our pilot study demonstrates feasibility for a "gold-standard" population-based study, to further explore and address disparities.Copyright © 2019

Background: Readmissions within 90-days post-stroke appear to be associated with comorbidities or disability-related issues based on the severity of the initial stroke. We describe patient and clinical factors associated with readmission to hospital within 90 days after discharge from stroke in the Australian setting. Method(s): We used person-level linkages between data from the Australian Stroke Clinical Registry (2009-2013), national death registrations and hospital admission data from Victoria, Queensland, New South Wales and Western Australia. Time to first readmission among patients with stroke discharged alive (excluding discharges to inpatient rehabilitation) was examined using competing risks regression accounting for death within 90-days. Covariates included age, ability to walk on admission (a measure of stroke severity), stroke type, stroke unit care, length of stay (LOS) and the Elixhauser Comorbidity Index (derived using ICD-10 coded admission data in the preceding 5-years). Result(s): Among 9,018 patients with stroke discharged (46% female; 79% ischaemic stroke), 20.7% were readmitted within 90-days. In univariable analyses readmission was associated with greater stroke severity, older age, shorter LOS and having more comorbidities, but not stroke unit care. After adjustment, factors independently associated with a greater risk of 90-day readmission were ability to walk on initial stroke presentation (HR 0.41, 95%CI:0.35, 0.48), older age (HR 1.89, 95%CI:1.77,2.02), intracerebral haemorrhage (HR 1.54 95%CI:1.31,1.80) and higher Elixhauser comorbidity scores (HR 1.40,95%CI:1.35,1.46). Conclusion(s): Older patients with higher number of comorbidities who are discharged to the community are at greater risk of early readmission. Alternative care pathways may be needed to better support this group.

Background: Retrospective data indicate increased stroke incidence in Aboriginal/Torres Strait Islander (Indigenous) Australians, possibly with poorer outcomes. We present the first prospective population-based stroke incidence study in Indigenous Australians. Method(s): We pooled data from ASCEND and SEARCH, two prospective "ideal" South Australian stroke incidence studies, ASCEND conducted in urban Northwestern Adelaide (2009-2010) and SEARCH in five South Australian rural centers (2009-2011). We calculated age-standardized incidence for Aboriginal and non-Aboriginal people. Result(s): The study population comprised 261,403 inhabitants. Among 432 first-ever strokes, 13 were in Aboriginal people (median age 51 vs. 78 years for non-Aboriginal people, p < 0.001). Age-standardized stroke incidence per 100,000 in Aboriginal patients (116, 95% CI: 95-137) was nearly two-fold that of non-Aboriginal patients (67, 95% CI: 51-84). Age-stratified excess incidence in Aboriginal people was restricted to those aged < 55 years (incidence rate ratio (IRR) 3.5, 95% CI: 2-7), particularly for intracerebral hemorrhage (IRR: 16, 95% CI: 4-61). Conclusion(s): The excess stroke incidence in Aboriginal South Australians appears substantial, especially in those aged <55 years. Further work is required to delineate and address disparities.Copyright © 2018 World Stroke Organization.

Background: Little is known about the factors that contribute to readmission after discharge from hospital following acute stroke or transient ischaemic attack. Aim(s): To describe the patient and clinical factors associated with all-cause readmission to hospital within 90 days after discharge from stroke. Method(s): Cohort design linking data from the Australian Stroke Clinical Registry (2009-2013), national death registration registry and hospital separations from Victoria, Queensland, New South Wales and Western Australia. Time to first readmission was examined using competing risks regression accounting for death within 90-days. Prior history of risk factors for stroke and prior comorbidities (using the Elixhauser Index) were derived using ICD-10 codes from separations data in the preceding 5-years. Result(s): Data for 13,676 patients were linked (45% female; 79% ischaemic stroke). Among 12,549 patients discharged (excluding discharges inpatient rehabilitation), 23% were readmitted within 90 days; 27% among those discharged directly to home. In univariable analyses readmission was associated with older age, being Australian born, greater stroke severity, shorter length of stay and having more risk factors or comorbidities, but not stroke unit care. After adjustment, factors independently associated with a higher rate of 90-day readmission were higher Elixhauser comorbidity scores (HR:1.09, 95%CI:1.05,1.14) and a history of hypertension (HR:1.33, 95%CI:1.09,1.63), smoking (HR:1.20,95%CI:1.08,1.35), high cholesterol (HR:1.20, 95%CI:1.07,1.36) or atrial fibrillation (HR:1.12, 95%CI:1.03,1.22). Conclusion(s): Patients with a larger burden of comorbidities and risk factors before stroke are at greater risk of readmission within 90 days after discharge. Closer follow-up of these patients is needed to reduce readmissions within 90 days.

Background: Comparisons of stroke mortality rates between hospitals may vary widely depending on the covariates used in adjustment. We aimed to determine whether linkage between the Australian Stroke Clinical Registry (AuSCR) and hospital separations data provides better explanation for variability in 30-day risk-adjusted mortality rates (RAMR) than conventional separations data alone. Method(s): Cohort design using patient-level linkages between the AuSCR (2009-2013), national death registrations and state separations data (Vic, Qld, NSW, WA). Prior comorbidities (Elixhauser Index) were derived from ICD-10 diagnosis codes. Hospitals with 200+ episodes per year were included. Generalised linear latent and mixed models were used to calculate RAMR for each hospital.We compared Model A (demographics, prior comorbidities), Model B (demographics, stroke severity, recurrent stroke) and Model C (covariates contained in Models A+B) using Bayesian information criterion (BIC) and C-statistic. Smaller BIC indicates better fit and C-Statistics between 0.7-0.79 show acceptable and 0.8-0.89 show excellent discrimination. Result(s): Of 8,852 episodes of care from 17 eligible hospitals, 980 (11%) patients died within 30 days of admission. Hospital RAMRs ranged from 4% to 15%. According to fit statistics Models B (BIC: 4225; C-statistic, 0.822) and C (BIC: 4242; C-statistic, 0.829) provided a better explanation than Model A (BIC: 5399; C-statistic, 0.762) on the basis of lower BIC and higher C-statistic. Conclusion(s): Addition of stroke severity and recurrent stroke to mortality models provides a better explanation of variation in RAMR compared to risk adjustment based on separations data alone. Use of the AuSCR enables improved validity of inter-hospital RAMR comparisons.

Background: Few data exist on premorbid hospital admissions and missed opportunities for stroke prevention. We aimed to determine the frequency and primary reason for admissions to hospital within 90-days prior to an intracerebral haemorrhage (ICH). Method(s): Cohort design using patient-level linkages from the Australian Stroke Clinical Registry (AuSCR) (2009-2013) and hospital separations data from Victoria, Queensland, New South Wales and Western Australia. A 90-day 'look-back' period was evaluated from the separations data and the principal diagnoses and comorbidities related to admissions prior to ICH were categorised from ICD-10 codes. Descriptive data are presented. Result(s): Among 13,676 registrants, 1816 (14%) had an ICH (51% male, 50% aged 75+ years, 81% first-ever events). Within 90-days prior to an ICH, 435 (24%) experienced 800 hospital admissions (median time to admission before ICH: 38 days). Diseases of the circulatory system were the most common principal diagnosis for these hospital admissions, occurring in 17% of patients; and 9% were for stroke/transient ischaemic attack (TIA). The most common principal diagnoses included: dialysis (13%), kidney disease (5%), rehabilitation procedure (4%), chemotherapy (4%), cerebral infarction (3%) and TIA (2%). Prior to ICH, many of these patients had coded stroke risk factors: 19% hypertension, 8% atrial fibrillation and 5% diabetes. Conclusion(s): One quarter of patients with ICH had an admission within 90-days prior to this major health event. Many of those admitted to hospital had important risk factors, especially hypertension, that possibly could have been more aggressively managed to mitigate subsequent ICH.

Some of the highest recorded rheumatic heart disease (RHD) prevalence and mortality rates are from the World Health Organization's Western Pacific Region (WPR). RHD burden has been well documented in much of the WPR subregion of Oceania, but less is known about RHD outside the Pacific Islands and Australasia. We aimed to review RHD burden in WPR outside Oceania to identify countries with high RHD burden and those with contemporary data gaps. We searched the peer-reviewed literature for English-language primary studies published between 1980 and April 2017 that reported RHD prevalence or mortality in the 13 WPR countries/areas outside Oceania, and Taiwan. We also searched for official government reports and health indicator documents. Results were synthesised narratively and reported stratified by 2015 Human Development Index (HDI) level. 30 peer-reviewed publications fulfilling inclusion criteria were identified, representing nine countries/areas. RHD prevalence and mortality have fallen in association with economic development, particularly in very high HDI countries. In several countries that have undergone recent economic development, RHD persists particularly among older populations. In poorer WPR countries there is a persistent RHD burden, including in young populations. Some countries had no available data. Although RHD burden has declined in many high-resource settings across the WPR, in several poorer countries, the impact of RHD appears to continue. Elsewhere, insufficient contemporary data make it difficult to gauge the current status of RHD burden and control. Concerted efforts are needed to fill information gaps and implement action to address this avoidable disease.

© 2016 Durey et al.Background: Effectively addressing health disparities between Aboriginal and non-Aboriginal Australians is long overdue. Health services engaging Aboriginal communities in designing and delivering healthcare is one way to tackle the issue. This paper presents findings from evaluating a unique strategy of community engagement between local Aboriginal people and health providers across five districts in Perth, Western Australia. Local Aboriginal community members formed District Aboriginal Health Action Groups (DAHAGs) to collaborate with health providers in designing culturally-responsive healthcare. The purpose of the strategy was to improve local health service delivery for Aboriginal Australians. Methods: The evaluation aimed to identify whether the Aboriginal community considered the community engagement strategy effective in identifying their health service needs, translating them to action by local health services and increasing their trust in these health services. Participants were recruited using purposive sampling. Qualitative data was collected from Aboriginal participants and health service providers using semi-structured interviews or yarning circles that were recorded, transcribed and independently analysed by two senior non-Aboriginal researchers. Responses were coded for key themes, further analysed for similarities and differences between districts and cross-checked by the senior lead Aboriginal researcher to avoid bias and establish reliability in interpreting the data. Three ethics committees approved conducting the evaluation. Results: Findings from 60 participants suggested the engagement process was effective: it was driven and owned by the Aboriginal community, captured a broad range of views and increased Aboriginal community participation in decisions about their healthcare. It built community capacity through regular community forums and established DAHAGs comprising local Aboriginal community members and health service re

Objective: To describe the challenges of obtaining state and nationally held data for linkage to a non-government national clinical registry. Methods: We reviewed processes negotiated to achieve linkage between the Australian Stroke Clinical Registry (AuSCR), the National Death Index, and state held hospital data. Minutes from working group meetings, national workshop meetings, and documented communications with health department staff were reviewed and summarised. Results: Time from first application to receipt of data was more than two years for most state data-sets. Several challenges were unique to linkages involving identifiable data from a non-government clinical registry. Concerns about consent, the re-identification of data, duality of data custodian roles and data ownership were raised. Requirements involved the development of data flow methods, separating roles and multiple governance and ethics approvals. Approval to link death data presented the fewest barriers. Conclusion: To our knowledge, this is the first time in Australia that person-level data from a clinical quality registry has been linked to hospital and mortality data across multiple Australian jurisdictions. Implications for Public Health: The administrative load of obtaining linked data makes projects such as this burdensome but not impossible. An improved national centralised strategy for data linkage in Australia is urgently needed.

Background/objectives: Little is known about trends in risk factors and mortality for Aboriginal Australians with heart failure (HF). This population-based study evaluated trends in prevalence of risk factors, 30-day and 1-year all-cause mortality following first HF hospitalization among Aboriginal and non-Aboriginal Western Australians in the decade 2000-2009. Methods: Linked-health data were used to identify patients (20-84 years), with a first-ever HF hospitalization. Trends in demographics, comorbidities, interventions and risk factors were evaluated. Logistic and Cox regression models were fitted to test and compare trends over time in 30-day and 1-year mortality. Results: Of 17,379 HF patients, 1,013 (5.8 %) were Aboriginal. Compared with 2000-2002, the prevalence (as history) of myocardial infarction and hypertension increased more markedly in 2006-2009 in Aboriginal (versus non-Aboriginal) patients, while diabetes and chronic kidney disease remained disproportionately higher in Aboriginal patients. Risk factor trends, including the Charlson comorbidity index, increased over time in younger Aboriginal patients. Risk-adjusted 30-day mortality did not change over the decade in either group. Risk-adjusted 1-year mortality (in 30-day survivors) was non-significantly higher in Aboriginal patients in 2006-2008 compared with 2000-2002 (hazard ratio (HR) 1.44; 95 % CI 0.85-2.41; p-trend = 0.47) whereas it decreased in non-Aboriginal patients (HR 0.87; 95 % CI 0.78-0.97; p-trend = 0.01). Conclusions: Between 2000 and 2009, the prevalence of HF antecedents increased and remained disproportionately higher in Aboriginal (versus non-Aboriginal) HF patients. Risk-adjusted 1-year mortality did not improve in Aboriginal patients over the period in contrast with non-Aboriginal patients. These findings highlight the need for better prevention and post-HF care in Aboriginal Australians.

Objectives The aim of the present study was to provide descriptive planning data for a hospital-based Aboriginal Health Liaison Officer (AHLO) program, specifically quantifying episodes of care and outcomes within 28 days after discharge. Methods A follow-up study of Aboriginal in-patient hospital episodes was undertaken using person-based linked administrative data from four South Metropolitan hospitals in Perth, Western Australia (2006-11). Outcomes included 28-day deaths, emergency department (ED) presentations and in-patient re-admissions. Results There were 8041 eligible index admissions among 5113 individuals, with episode volumes increasing by 31% over the study period. Among patients 25 years and older, the highest ranking comorbidities included injury (47%), drug and alcohol disorders (41%), heart disease (40%), infection (40%), mental illness (31%) and diabetes (31%). Most events (96%) ended in a regular discharge. Within 28 days, 24% of events resulted in ED presentations and 20% resulted in hospital re-admissions. Emergency readmissions (13%) were twice as likely as booked re-admissions (7%). Stratified analyses showed poorer outcomes for older people, and for emergency and tertiary hospital admissions. Conclusions Future planning must address the greater service volumes anticipated. The high prevalence of comorbidities requires intensive case management to address case complexity. These data will inform the refinement of the AHLO program to improve in-patient experiences and outcomes. What is known about the topic? The health gap between Aboriginal and non-Aboriginal Australians is well documented. Aboriginal people have significantly higher hospital utilisation rates, as well as higher rates of complications, comorbidities and discharges against medical advice (DAMA). Aboriginal patients receive most of their specialist services in hospital; however, detailed person-based analyses are limited and planning is often based on crude data. What does this pa

Objectives: To compare the incidence of first heart failure (HF) hospitalisation, antecedent risk factors and 1-year mortality between Aboriginal and non-Aboriginal populations in Western Australia (2000–2009). Methods: A population-based cohort aged 20–84 years comprising Aboriginal (n = 1013; mean 54 ± 14 years) and non-Aboriginal patients (n = 16,366; mean 71 ± 11 years) with first HF hospitalisation was evaluated. Age and sex-specific incidence rates and HF antecedents were compared between subpopulations. Regression models were used to examine 30-day and 1-year (in 30-day survivors) mortality. Results: Aboriginal patients were younger, more likely to reside in rural/remote areas (76% vs 23%) and to be women (50.6% vs 41.7%, all p < 0.001). Aboriginal (versus non-Aboriginal) HF incidence rates were 11-fold higher in men and 23-fold in women aged 20–39 years, declining to about 2-fold in patients aged 70–84 years. Ischaemic and rheumatic heart diseases were more common antecedents of HF in younger (< 55 years) Aboriginal versus non-Aboriginal patients (p < 0.001). Hypertension, diabetes, chronic kidney disease, renal failure, chronic obstructive pulmonary disease, and a high Charlson comorbidity index (>= 3) were also more prevalent in younger and older Aboriginal patients (p < 0.001). Although 30-day mortality was similar in both subpopulations, Aboriginal patients aged < 55 years had a 1.9 risk-adjusted hazard ratio (HR) for 1-year mortality (p = 0.015). Conclusions: Aboriginal people had substantially higher age and sex-specific HF incidence rate and prevalence of HF antecedents than their non-Aboriginal counterparts. HR for 1-year mortality was also significantly worse at younger ages, highlighting the urgent need for enhanced primary and secondary prevention of HF in this population.

DUREY A, WYNADEN D, THOMPSON SC, DAVIDSON PM, BESSARAB D and KATZENELLENBOGEN JM. Nursing Inquiry 2012; 19: 144152 [Epub ahead of print] Owning solutions: a collaborative model to improve quality in hospital care for Aboriginal Australians Well-documente

In our effort to develop imaging agents for brain glucocorticoid receptors, we have prepared several novel glucocorticoids possessing a 2-methylsulfanyl-acetyl side chain. The synthesis was accomplished via a Mitsunobu reaction with thiobenzoic acid starting from cortisol, prednisolone, dexamethasone and triamcinolone acetonide to give the corresponding S-thiobenzoates in 75-82% yield. Subsequent saponification and reaction with methyl iodide afforded C-21 methylthioethers in 68-82% yield. All compounds were tested in an in vitro glucocorticoid receptor binding assay. Triamcinolone acetonide-based compound 12 showed promising binding affinity of 144% relative to dexamethasone (100%). Compound 12 was selected for radiolabeling with the short-lived positron emitter carbon-11. The radiolabeling was carried out starting from S-thiobenzoate 8 and in situ formation of the corresponding sodium thiolate, which was further reacted with [11C]methyl iodide. The obtained radiochemical yield was 20-30%. The specific activity was determined to be 20-40 GBq/µmol at the end-of-synthesis, and the radiochemical purity exceeded 98%.

Sigma receptors are membrane-bound proteins having high affinities for a variety psychotropic drugs with opiate-type structures. The sigma receptor subtypes, sigma-1 and sigma-2, have different molecular weights and pharmacological roles.1 Many cancer cell lines (breast, melanoma, prostate cancer) express high levels of sigma receptors,2,3 and proliferative tumor cells express much higher levels of sigma-2 receptors than quiescent cells.4,5 Thus, the sigma-2 receptor has been proposed as a suitable target for imaging proliferative tumor cells. While many ligands are selective for the sigma-1 receptor or are nonselective, very few ligands are selective for the sigma-2 receptor. A radiopharmaceutical based on an azabicyclo[3.3.1]nonane framework was developed by Mach,6 who demonstrated that the rhenium surrogate showed exceptional sigma-2 selectivity; later this agent was labeled with technetium-99m by Kung for tissue distribution studies.7 In considering potential fluorine-18 labeled sigma-2 receptor ligands, our attention focused on members of an indole piperidine series, especially 1 (LU 28-179), which is reported to have a remarkably high sigma-2 binding affinity and selectivity.8,9 Figure 1. The structure of indole piperidine ligands and their inhibition constants toward sigma receptors. Target compounds 1 and 2 were prepared in several steps by a route based on a previously described method,7 with modifications making it more efficient for the synthesis of the precursor molecule (3); compounds 1 and 2 showed high binding affinity and good selectivity (6 fold) for the sigma-2 receptor (Figure 1). The preparation of [18F]-labeled indole piperidine [18F]1 was achieved in two steps from a o-nitroaldehyde precursor (3). Aromatic [18F]fluorination was not reproducible when 3 was treated with F-18 fluoride in the presence of Bu4NOH under microwave heating conditions. However, by using F-18, K2CO3 and kryptofix[2.2.

Corticosteroids regulate a variety of essential physiological functions, such as mineral balance and stress. The great interest in these steroids, especially the glucocorticoids, stems from roles they are thought to play in neuropsychiatric disorders, such as severe depression and anxiety. The development of glucocorticoid receptor (GR) ligands which are appropriately labeled with short-lived positron-emitting radioisotopes would allow the non-invasive in-vivo imaging and mapping of brain GRs by means of positron emission tomography (PET). In this context we have synthesized a series of novel arylpyrazolo steroids exhibiting different substitution patterns at the D-ring of the steroid skeleton, as ligands for brain GRs. Special attention was given to 4-fluorophenyl pyrazolo steroids, which are known to display high binding affinity toward the GR. The compounds were evaluated in a competitive radiometric receptor binding assay to determine their relative binding affinities (RBA) to the GR. Some compounds show good binding affinities of up to 56% in comparison to dexamethasone (100%). In initial experiments, selected candidates were labeled with the positron emitter fluorine-18 and in one case with the gamma-emitter iodine-131.

The diagnosis and staging of breast cancer could be improved by the development of radiopharmaceutical imaging agents that provide a noninvasive determination of the estrogen receptor (ER) status of tumor cells. Agents labeled with 99mTc would be especially valuable in this regards. In attempting to achieve this goal, we synthesized four 99mTc-labeled 7alpha-substituted estradiol complexes. One complex utilizes the "3+1" mixed ligand design to introduce the Tc metal, whereas the other three took advantage of the cyclopentadienyltricarbonylmetal (CpTM) design. The Tc moieties were attached to the 7alpha position of estradiol with a hexyl tether, a monoether tether, or a polyether tether. The corresponding rhenium compounds have binding affinities for the ER of 20-45% compared with estradiol. Radiochemical yields of the

The diagnosis and staging of breast cancer could be improved by the development of imaging radiopharmaceuticals that provide a non-invasive determination of the estrogen receptor (ER) status of tumor cells. Towards this goal, we have synthesized a number of Re and Tc-labeled estradiol (1) mimics based on the conjugated design, which tethers a metal-containing moiety to an existing steroid. In this study, the 7alpha position of estradiol was chosen as the tether site, due to its well known tolerance of bulky substituents. 1 The metal was stabilized using either the "3+1" design (2,3), or the cyclopentadienyltricarbonylmetal (CpTM) approach (4,5,6) . In the "3+1" design, a tridentate ligand and a monodentate ligand surround an oxometal core.2 In the CpTM design, a substituted Cp and three carbonyls are coordinated to a Re/Tc(I) center.3,4 The advantages of using the "3+1" and CpTM desings are the well-established stability of both systems, as well as the ability to produce both systems efficiently at the tracer level.2,4 The first tether used was a hexyl spacer, and the synthesis of the precursors for targets 2-6 started with THP-protected estradiol 7 (Scheme 1). After oxidation to ketone 8 using a previously published method,

The diagnosis and staging of breast cancer could be improved by the development of imaging radiopharmaceuticals that provide a noninvasive determination of the estrogen receptor status in the tumor cells. Toward this goal, we have synthesized a number of novel Re-containing 7alpha-substituted estradiol complexes. The introduction of the 7alpha side chain involves the alkylation of tetrahydropyranyloxy-protected 6-keto estradiol. The methods used to introduce the rhenium metal involve "3+1" and "4+1" mixed ligand complexes (2a-c and 5, respectively), tricarbonyl dithioether complexes (3), and the cyclopentadienyltricarbonylmetal organometallic system (4ab, 6, 7). These complexes showed binding affinities for the estrogen receptor (as high as 45% for the "3+1" complex 2c) when compared to the native ligand estradiol. The polarity of some complexes (4ab) was modified to improve biodistribution properties by introducing (poly)ether linkages into the 7alpha side chain (6, 7). These complexes provide a further refinement of our understanding of ligand structure-binding affinity correlations for the estrogen receptor, and they furnish the synthetic groundwork for the synthesis of the analogous Tc-99m complexes for evaluation as breast tumor imaging agents.

To assist in the development of technetium-based radiopharmaceuticals that are useful for the diagnostic imaging of steroid receptor-positive breast tumors, we have synthesized a series of small-sized metal chelates according to 'n+1' mixed ligand, thioether-carbonyl and organometallic designs. In these preliminary investigations, rhenium was used as a model for the radioactive technetium. The metal chelates contain the rhenium metal in several oxidation states, being +5, +3, and +1, and they were attached to 21-substituted progesterone derivatives. A competitive receptor-binding assay (rat uterine cytosol, 0°C) was used to determine the binding affinity of these conjugates for the progesterone receptor. The highest affinity of 9% (RU5020=100%) was obtained with a '3+1' mixed-ligand complex, containing a NMe group as the central donor atom in the tridentate ligand part. This value reflects a relative binding affinity of 75% compared with the parent steroid progesterone.

A series of rhenium "n+1" mixed-ligand, thioether-carbonyl and organometallic complexes of 21-substituted progesterone have been synthesized. The conjugates contain the rhenium metal at several oxidation states, being +5, +3 and +1. The complexes were used in a competitive receptor-binding assay (rat-uterus, 0°C) to determine their binding to the progesterone receptor. The best affinity of 9% (RU 5020=100%) was obtained with a "3+1" mixed-ligand complex, containing a NMe group as the central donor atom in the tridentate ligand part.

The gonadal steroids are implicated in hormone-dependent cancers of the breast and prostate. In order to image estrogen receptor positive tumors by using 99mTc based radiopharmaceuticals, we have synthesized novel rhenium(V), (III) and (i) complexes of 17Alpha-substituted estradiol. In our first investigations we used rhenium as a model for the radioactive technetium. These complexes represent new classes of estrogen receptor-binding rhenium complexes. The binding affinities (lamb-cytosol) at 0°C reveal RBA values of about 23% for the oxorhenium(V) complexes when X = O and 8% when X = S. The RBA values at 25°C are 10% for the oxorhenium(V) complexes when X = O and 15% when X = S. For the rhenium(III) and rhenium(I) complexes the RBA values are significantly lower for 0°C and 25°C, ranging from 0.6% to 2.5%. Further studies will investigate the stability of these complexes under in vivo conditions using the corresponding 99mTc-complexes.