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Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life and longevity. The epidemiology of VHD varies substantially around the world, with a predominance of functional and degenerative disease in high-income countries, and a predominance of rheumatic heart disease in low-income and middle-income countries. Reflecting this distribution, rheumatic heart disease remains by far the most common manifestation of VHD worldwide and affects approximately 41 million people. By contrast, the prevalence of calcific aortic stenosis and degenerative mitral valve disease is 9 and 24 million people, respectively. Despite a reduction in global mortality related to rheumatic heart disease since 1900, the death rate has remained fairly static since 2000. Meanwhile, deaths from calcific aortic stenosis have continued to rise in the past 20 years. Epidemiological data on other important acquired and congenital forms of VHD are limited. An ageing population and advances in therapies make an examination of the changing global epidemiology of VHD crucial for advances in clinical practice and formulation of health policy. In this Review, we discuss the global burden of VHD, geographical variation in the presentation and clinical management, and temporal trends in disease burden. Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life and longevity. In this Review, Prendergast and colleagues discuss the global burden of VHD, geographical variation in the presentation and clinical management, and temporal trends in disease burden.

Indigenous children and young peoples live with an inequitable burden of acute rheumatic fever and rheumatic heart disease. In this Review, we focus on the epidemiological burden and lived experience of these conditions for Indigenous young peoples in Australia, New Zealand, and Canada. We outline the direct and indirect drivers of rheumatic heart disease risk and their mitigation. Specifically, we identify the opportunities and limitations of predominantly biomedical approaches to the primary, secondary, and tertiary prevention of disease among Indigenous peoples. We explain why these biomedical approaches must be coupled with decolonising approaches to address the underlying cause of disease. Initiatives underway to reduce acute rheumatic fever and rheumatic heart disease in Australia, New Zealand, and Canada are reviewed to identify how an Indigenous rights-based approach could contribute to elimination of rheumatic heart disease and global disease control goals.

Type 2 diabetes mellitus (T2DM) increases cardiac inflammation which promotes the development of cardiac fibrosis. We sought to determine the impact of circadian disruption on the induction of hyperglycaemia, inflammation and cardiac fibrosis. Methods: Psammomys obesus (P. obesus) were exposed to neutral (12 h light:12 h dark) or short (5 h light:19 h dark) photoperiods and fed a low energy (LE) or high energy (HE) diet for 8 or 20 weeks. To determine daily rhythmicity, P. obesus were euthanised at 2, 8, 14, and 20 h after ‘lights on’. Results: P. obesus exposed to a short photoperiod for 8 and 20 weeks had impaired glucose tolerance following oral glucose tolerance testing, compared to a neutral photoperiod exposure. This occurred with both LE and HE diets but was more pronounced with the HE diet. Short photoperiod exposure also increased myocardial perivascular fibrosis after 20 weeks on LE (51%, P P Nppa (atrial natriuretic peptide) and hypertrophy transcription factors Gata4 and Mef2c in myocardial tissue after 8 weeks. Conclusion: Exposure to a short photoperiod causes impaired glucose tolerance in P. obesus that is exacerbated with HE diet and is accompanied by an induction in myocardial perivascular fibrosis.

Diabetes is a major burden on Australia’s Indigenous population, with high rates of disease and vascular complications. Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. MicroRNAs (miRNAs) are key players in the regulation of angiogenesis. HDL-cholesterol (HDL-c) levels are inversely associated with the risk of developing diabetic complications and HDL can carry miRNAs. HDL-miRNA profiles differ in disease states and may present as biomarkers with the capacity to act as bioactive signalling molecules. Recent studies have demonstrated that HDL becomes dysfunctional in a diabetic environment, losing its vasculo-protective effects and becoming more pro-atherogenic. We sought to determine whether HDL-associated miRNA profiles and HDL functionality were predictive of the severity of diabetic vascular complications in Australia’s Indigenous population. HDL was isolated from plasma samples from Indigenous participants without diabetes (‘Healthy’), with type 2 diabetes mellitus (‘T2DM’) and with diabetes-associated macrovascular complications (specifically peripheral artery disease, ‘T2DM+Comp’). To assess HDL angiogenic capacity, human coronary artery endothelial cells were treated with PBS, reconstituted HDL (rHDL, positive control) or isolated HDL and then exposed to high-glucose (25 mmol/l) conditions. The expression levels of two anti-angiogenic miRNAs (miR-181c-5p and miR-223-3p) and one pro-angiogenic miRNA (miR-27b-3p) were measured in the HDL fraction, plasma and treated human coronary artery endothelial cells by quantitative real-time PCR. In vitro endothelial tubule formation was assessed using the Matrigel tubulogenesis assay. Strikingly, we found that the levels of the anti-angiogenic miRNA miR-181c-5p were 14-fold higher (1454 ± 1346%) in the HDL from Aboriginal people with diabetic complications compared with both the Healthy (100 ± 121%, p

Background Chronic diseases are the leading contributor to the excess morbidity and mortality burden experienced by Aboriginal and Torres Strait Islander (hereafter, respectfully, Indigenous) people, compared to their non-Indigenous counterparts. The Home-based Outreach case Management of chronic disease Exploratory (HOME) Study provided person-centred, multidisciplinary care for Indigenous people with chronic disease. This model of care, aligned to Indigenous peoples’ conceptions of health and wellbeing, was integrated within an urban Indigenous primary health care service. We aimed to determine the impact of this model of care on participants’ health and wellbeing at 12 months. Methods HOME Study participants were Indigenous, regular patients of the primary health care service, with a diagnosis of at least one chronic disease, and complex health and social care needs. Data were collected directly from participants and from their medical records at baseline, and 3, 6 and 12 months thereafter. Variables included self-rated health status, depression, utilisation of health services, and key clinical outcomes. Participants’ baseline characteristics were described using frequencies and percentages. Generalized estimating equation (GEE) models were employed to evaluate participant attrition and changes in outcome measures over time. Results 60 participants were enrolled into the study and 37 (62%) completed the 12-month assessment. After receiving outreach case management for 12 months, 73% of participants had good, very good or excellent self-rated health status compared with 33% at baseline (p p = 0.03). Significant increases in appointments with allied health professionals (p p = 0.001) were observed at 12-months compared with baseline rates. Mean systolic blood pressure decreased over time (p = 0.02), but there were no significant changes in mean HbA1c, body mass index, or diastolic blood pressure. Conclusions The HOME Study model of care was predicated on a holistic conception of health and aimed to address participants’ health and social care needs. The positive changes in self-rated health and rates of depression evinced that this aim was met, and that participants received the necessary care to support and improve their health and wellbeing.

Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By comparison, less is known about pathogenic DNA variants in people from other parts of the world. Consequently, inclusion of currently underrepresented Indigenous and other minority population groups in genomic research is essential to enable equitable outcomes in ECS and other areas of genomic medicine. Here, we discuss this issue in relation to the implementation of ECS in Australia, which is currently being evaluated as part of the national Government’s Genomics Health Futures Mission. We argue that significant effort is required to build an evidence base and genomic reference data so that ECS can bring significant clinical benefit for many Aboriginal and/or Torres Strait Islander Australians. These efforts are essential steps to achieving the Australian Government’s objectives and its commitment “to leveraging the benefits of genomics in the health system for all Australians.” They require culturally safe, community-led research and community involvement embedded within national health and medical genomics programs to ensure that new knowledge is integrated into medicine and health services in ways that address the specific and articulated cultural and health needs of Indigenous people. Until this occurs, people who do not have European ancestry are at risk of being, in relative terms, further disadvantaged.

Electron-donating N-heterocyclic carbenes (Lewis bases, LB) and electron-accepting Lewis acids (LA) have been used in tandem to yield donor-acceptor complexes of inorganic tetrelenes LB·EH2·LA (E = Si, Ge, and Sn). Herein, we introduce the new germanium (II) dihydride adducts ImMe2·GeH2·BH3 (ImMe2 = (HCNMe)2C:) and ImiPr2Me2·GeH2·BH3 (ImiPr2Me2 = (MeCNiPr)2C:), with the former complex containing nearly 40 wt % germanium. The thermal release of bulk germanium from ImMe2·GeH2·BH3 (and its deuterated isotopologue ImMe2·GeD2·BD3) was examined in solution, and a combined kinetic and computational investigation was undertaken to probe the mechanism by which Ge is liberated. Moreover, the thermolysis of ImMe2·GeH2·BH3 in solution cleanly affords conformal nanodimensional layers of germanium as thin films of variable thicknesses (20-70 nm) on silicon wafers. We also conducted a computational investigation into potential decomposition pathways for the germanium(II)- and tin(II)-dihydride complexes NHC·EH2·BH3 (NHC = [(HCNR)2C:]; R = 2,6-iPr2C6H3 (Dipp), Me, and H; and E = Ge and Sn). Overall, this study introduces a mild and convenient solution-only protocol for the deposition of thin films of Ge, a widely used semiconductor in materials research and industry.

Objectives To assess long term outcomes for Aboriginal and Torres Strait Islander (Indigenous) Australians admitted non-electively to intensive care units (ICUs). Design Data linkage cohort study; analysis of ICU patient data (Australian and New Zealand Intensive Care Society Adult Patient Database), prospectively collected during 2007-2016. Setting All four university-affiliated level 3 ICUs in South Australia. Main outcomes Mortality (in-hospital, and 12 months and 8 years after admission to ICU), by Indigenous status. Results 2035 of 39 784 non-elective index ICU admissions (5.1%) were of Indigenous Australians, including 1461 of 37 661 patients with South Australian residential postcodes. The median age of Indigenous patients (45 years; IQR, 34-57 years) was lower than for non-Indigenous ICU patients (64 years; IQR, 47-76 years). For patients with South Australian postcodes, unadjusted mortality at discharge and 12 months and 8 years after admission was lower for Indigenous patients; after adjusting for age, sex, diabetes, severity of illness, and diagnostic group, mortality was similar for both groups at discharge (adjusted odds ratio [aOR], 0.95; 95% CI, 0.81-1.10), but greater for Indigenous patients at 12 months (aOR, 1.14; 95% CI, 1.03-1.26) and 8 years (adjusted hazard ratio, 1.23; 95% CI, 1.13-1.35). The number of potential years of life lost was greater for Indigenous patients (median, 24.0; IQR, 15.8-31.8 v 12.5; IQR, 0-22.3), but, referenced to respective population life expectancies, relative survival at 8 years was similar (proportions: Indigenous, 0.78; 95% CI, 0.75-0.80; non-Indigenous, 0.77; 95% CI, 0.76-0.78). Conclusions Adjusted long term mortality and median number of potential life years lost are higher for Indigenous than non-Indigenous patients after intensive care in hospital. These differences reflect underlying population survival patterns rather than the effects of ICU admission.

Addressing Indigenous rights and interests in genetic resources has become increasingly challenging in an open science environment that promotes unrestricted access to genomic data. Although Indigenous experiences with genetic research have been shaped by a series of negative interactions, there is increasing recognition that equitable benefits can only be realized through greater participation of Indigenous communities. Issues of trust, accountability and equity underpin Indigenous critiques of genetic research and the sharing of genomic data. This Perspectives article highlights identified issues for Indigenous communities around the sharing of genomic data and suggests principles and actions that genomic researchers can adopt to recognize community rights and interests in data.

Additive manufacturing/3D printing is a rapidly maturing field with potential advantages for the fabrication of chemical processing equipment. A demonstration of the molybdenum solvent-extr...

Issue addressed Noncommunicable chronic disease underlies much of the life expectancy gap experienced by Aboriginal and Torres Strait Islander people. Modifying contributing risk factors; tobacco smoking, nutrition, alcohol consumption, physical activity, social and emotional wellbeing (SNAPS) could help close this disease gap. This scoping review identified and describes SNAPS health promotion programs implemented for Aboriginal and Torres Strait Islander people in Australia. Methods Databases PubMed, CINAHL, Informit (Health Collection and Indigenous Peoples Collection), Scopus, Trove and relevant websites and clearing houses were searched for eligible studies until June 2015. To meet the inclusion criteria the program had to focus on modifying one of the SNAPS risk factors and the majority of participants had to identify as being of Aboriginal and/or Torres Strait Islander heritage. Results The review identified 71 health promotion programs, described in 83 publications. Programs were implemented across a range of health and community settings and included all Australian states and territories, from major cities to remote communities. The SNAPS factor addressed most commonly was nutrition. Some programs included the whole community, or had multiple key audiences, whilst others focused solely on one subgroup of the population such as chronic disease patients, pregnant women or youth. Fourteen of the programs reported no outcome assessments. Conclusions Health promotion programs for Aboriginal and Torres Strait Islander people have not been adequately evaluated. The majority of programs focused on the development of individual skills and changing personal behaviours without addressing the other health promotion action areas, such as creating supportive environments or reorienting health care services. So What? This scoping review provides a summary of the health promotion programs that have been delivered in Australia for Aboriginal and Torres Strait Islander people to prevent or manage chronic disease. These programs, although many are limited in quality, should be used to inform future programs. To improve evidence‐based health promotion practice, health promotion initiatives need to be evaluated and the findings published publicly.

Background Aboriginal and Torres Strait Islander women experience high rates of diabetes in pregnancy (DIP), contributing to health risks for mother and infant, and the intergenerational cycle of diabetes. By enhancing diabetes management during pregnancy, postpartum and the interval between pregnancies, the DIP Partnership aims to improve health outcomes and reduce risks early in the life-course. We describe a mixed methods formative study of health professional’s perspectives of antenatal and post-partum diabetes screening and management, including enablers and barriers to care. Methods Health professionals involved in providing diabetes care in pregnancy, from a range of health services across the Northern Territory, completed the survey (n = 82) and/or took part in interviews and/or focus groups (n = 62). Results Qualitative findings highlighted factors influencing the delivery of care as reported by health professionals, including: whose responsibility it is, access to care, the baby is the focus and pre-conception care. The main challenges were related to: disjointed systems and confusion around whose role it is to provide follow-up care beyond six weeks post-partum. Quantitative findings indicated that the majority of health professionals reported confidence in their own skills to manage women in the antenatal period (62%, 40/79) and slightly lower rates of confidence in the postpartum interval (57%, 33/58). Conclusion These findings regarding whose role it is to provide postpartum care, along with opportunities to improve communication pathways and follow up care have informed the design of a complex health intervention to improve health systems and the provision of DIP related care.

Background Aboriginal and Torres Strait Islander Australians have poorer cancer outcomes than other Australians. Comparatively little is known of the type and amount of cancer treatment provided to Aboriginal and Torres Strait Islander people and the consequences for cancer survival. This study quantifies the influence of surgical, systemic and radiotherapy treatment on risk of cancer death among matched cohorts of cancer cases and, the comparative exposure of cohorts to these treatments. Methods Cancers registered among Aboriginal South Australians in 1990–2010 (N = 777) were matched with randomly selected non-Indigenous cases by sex, birth and diagnostic year, and primary site, then linked to administrative cancer treatment for the period from 2 months before to 13 months after diagnosis. Competing risk regression summarised associations of Indigenous status, geographic remoteness, comorbidities, cancer stage and treatment exposure with risk of cancer death. Results Fewer Aboriginal cases had localised disease at diagnosis (37.2% versus 50.2%) and they were less likely to: experience hospitalisation with cancer diagnosis, unadjusted odds ratio (UOR) = 0.76; 95%CI = 0.59–0.98; have surgery UOR = 0.65; 95%CI = 0.53–0.80; systemic therapies UOR = 0.64; 95%CI = 0.52–0.78; or radiotherapy, UOR = 0.76; 95%CI = 0.63–0.94. Localised disease carried lower risk of cancer death compared to advanced cases receiving surgery or systemic therapies, SHR = 0.34; 95%CI = 0.25–0.47 and SHR = 0.35; 95%CI = 0.25–0.48. Advanced disease and no treatment carried higher risk of cancer death, SHR = 1.82; 95%CI = 1.26–2.63. Conclusion The effects of treatment did not differ between Aboriginal and non-Indigenous cohorts. However, comparatively less exposure to surgical and systemic treatments among Aboriginal cancer cases further complicated the disadvantages associated with geographic remoteness, advanced stage of disease and co-morbid conditions at diagnosis and add to disparities in cancer death. System level responses to improving access, utilisation and quality of effective treatments are needed to improve survival after cancer diagnosis.

Objective: To identify successes to date and opportunities for improvement in the implementation of a complex health systems intervention aiming to improve prenatal and postpartum care and health outcomes for women with hyperglycemia in pregnancy in regional and remote Australia. Methods: A qualitative evaluation, underpinned by the RE-AIM framework (reach, effectiveness, adoption, implementation, maintenance), was conducted mid-intervention. Semi-structured interviews were conducted with the participants, who included clinicians, regional policymakers and managers, and study implementation staff. Results: Interviewees (n = 45) reported that the early phase of the intervention had resulted in the establishment of a clinician network, increased clinician awareness of hyperglycemia in pregnancy, and improvements in management, including earlier referral for specialist care and a focus on improving communication with women. Enablers of implementation included existing relationships with stakeholders and alignment of the intervention with health service priorities. Challenges included engaging remote clinicians and the labor-intensive nature of maintaining a clinical register of women with hyperglycemia in pregnancy. Conclusion: The early phase of this health systems intervention has had a positive perceived impact on systems of care for women with hyperglycemia in pregnancy. Findings have informed modifications to the intervention, including the development of a communication and engagement strategy.

BackgroundCancer control initiatives are informed by quantifying the capacity to reduce cancer burden through effective interventions. Burden measures using health administrative data are a sustainable way to support monitoring and evaluating of outcomes among patients and populations. The PREmature Mortality to IncidencE Ratio (PREMIER) is one such burden measure. We use data on Aboriginal and non-Aboriginal South Australians from 1990 to 2010 to show how PREMIER quantifies disparities in cancer burden: between populations; between sub-population cohorts where stage at diagnosis is available; and when follow-up is constrained to 24-months after diagnosis.MethodPREMIERcancer is the ratio of years of life expectancy lost due to cancer (YLLcancer) to life expectancy years at risk at time of cancer diagnosis (LYAR) for each person. The Global Burden of Disease standard life table provides referent life expectancies. PREMIERcancer was estimated for the population of cancer cases diagnosed in South Australia from 1990 to 2010. Cancer stage at diagnosis was also available for cancers diagnosed in Aboriginal people and a cohort of non-Aboriginal people matched by sex, year of birth, primary cancer site and year of diagnosis.ResultsCancers diagnoses (N=144,891) included 777 among Aboriginal people. Cancer burden described by PREMIERcancer was higher among Aboriginal than non-Aboriginal (0.55, 95%CIs 0.52-0.59 versus 0.39, 95%CIs 0.39-0.40). Diagnoses at younger ages among Aboriginal people, 7 year higher LYAR (31.0, 95%CIs 30.0-32.0 versus 24.1, 95%CIs 24.1-24.2) and higher premature cancer mortality (YLLcancer=16.3, 95%CIs 15.1-17.5 versus YLLcancer=8.2, 95%CIs 8.2-8.3) influenced this. Disparities in cancer burden between the matched Aboriginal and non-Aboriginal cohorts manifested 24-months after diagnosis with PREMIERcancer 0.44, 95%CIs 0.40-0.47 and 0.28, 95%CIs 0.25-0.31 respectively.ConclusionPREMIER described disproportionately higher cancer burden among Aboriginal people in comparisons involving: all people diagnosed with cancer; the matched cohorts; and, within groups diagnosed with same staged disease. The extent of disparities were evident 24-months after diagnosis. This is evidence of Aboriginal peoples’ substantial capacity to benefit from cancer control initiatives, particularly those leading to earlier detection and treatment of cancers. PREMIER’s use of readily available, person-level administrative records can help evaluate health care initiatives addressing this need.

Aim: In the crowded field of leadership research, Indigenous leadership remains under-researched. This article explores the Leadership Model of an Aboriginal Community Controlled Primary Health Care Organisation providing services to the Yolngu people of remote northern Australia: the Miwatj Health Aboriginal Corporation (Miwatj). Background: The limited research which does exist on Indigenous leadership points to unique challenges for Indigenous leaders. These challenges relate to fostering self-determination in their communities, managing significant community expectations, and navigating a path between culturally divergent approaches to management and leadership. Methods: Guided by Indigenous methodology and using a mixed methods approach, semi-structured interviews, self-reported health service data, organisational and publicly available documents, and literature were analysed using a framework method of thematic analysis to identify key themes of the Miwatj Leadership Model. Findings: The Miwatj Leadership Model is underpinned by three distinctive elements: it offers Yolngu people employment opportunities; it supports staff who want to move into leadership positions and provides capacity building through certificates and diplomas; and it provides for the physical, emotional, and cultural wellbeing of all Yolngu staff. Furthermore, the model respects traditional Yolngu forms of authority and empowers the community to develop, manage and sustain their own health. The Miwatj Leadership Model has been successful in providing formal pathways to support Indigenous staff to take on leadership roles, and has improved the accessibility and acceptability of health care services as a result of Yolngu employment and improved cultural safety. Conclusions: Translating the Miwatj Leadership Model into other health services will require considerable thought and commitment. The Miwatj Leadership Model can be adapted to meet the needs of other health care services in consideration of the unique context within which they operate. This study has demonstrated the importance of having a formal leadership model that promotes recruitment, retention, and career progression for Indigenous staff.

Background There are major health disparities between Indigenous and non-Indigenous Australians. To address this, it is vital to understand the landscape of Indigenous trial activity. Methods We extracted data from all Australian trials registered between 2008-2018 on the Australian New Zealand Clinical Trials Registry or ClinicalTrials.gov. Indigenous-focused trials were identified by searching for relevant terms such as ‘Indigenous’ and ‘Aboriginal’. Indigenous versus non-Indigenous trials and Australian trials overall were compared by conditions studied, intervention type, study design and funding. Results Of the 9206 included trials, 139 (1.5%) focused on Indigenous health, and these were mostly in ‘Public Health’ (n = 69, 50%), ‘Mental Health’ (n = 35, 25%) and ‘Cardiovascular’ (n = 25, 18%) (Figure). Compared to other Australian trials, Indigenous trials more frequently studied ear conditions (OR 16.47, 95%CI=8.43-29.99) and public health (OR 4.87, 95%CI=3.65-6.41), and were more likely to focus on screening (OR 3.57, 95%CI=2.10-5.70) and prevention (OR 2.24, 95%CI=1.61-3.08) rather than treatment (OR 0.40, 95%CI =0.30-0.52). They were less likely to be blinded (OR 1.72, 95%CI=1.20-2.49), or have any industry involvement (OR 2.52, 95%CI=1.54-4.43). Conclusions Indigenous trials differed from other Australian trials in health conditions studied, intervention focus, blinding and industry involvement. Relative to population size and burden of disease, the number of trials focusing on Indigenous health is low. Key messages Trial registries can be used to explore whether research appropriately addresses diverse populations such as Indigenous Australians. This can inform future research prioritisation.

It is critical that health service evaluation frameworks include Aboriginal people and their cultural worldviews from design to implementation. During a large participatory action research study, Elders, service leaders and Aboriginal and non-Aboriginal researchers co-designed evaluation tools to test the efficacy of a previously co-designed engagement framework. Through a series of co-design workshops, tools were built using innovative collaborative processes that foregrounded Aboriginal worldviews. The workshops resulted in the development of a three-way survey that records the service experiences related to cultural safety from the perspective of Aboriginal clients, their carer/s, and the service staff with whom they work. The surveys centralise the role of relationships in client-service interactions, which strongly reflect their design from an Aboriginal worldview. This paper provides new insights into the reciprocal benefits of engaging community Elders and service leaders to work together to develop new and more meaningful ways of servicing Aboriginal families. Foregrounding relationships in service evaluations reinstates the value of human connection and people-centred engagement in service delivery which are central to rebuilding historically fractured relationships between mainstream services and Aboriginal communities. This benefits not only Aboriginal communities, but also other marginalised populations expanding the remit of mainstream services to be accessed by many. Refereed/Peer-reviewed

To assess associations of hyperglycemia in pregnancy with the risk of postpartum hemorrhage (PPH) in a prospective cohort of Indigenous and non-Indigenous women, compared with normoglycemia.Data were from 1102 (48% Indigenous) women of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study. Age-adjusted associations of gestational diabetes mellitus (GDM) or pre-existing type 2 diabetes mellitus (T2DM), obstetric and demographic covariables with PPH (blood loss ≥500 ml) were assessed using logistic regression. Multivariable-adjusted models included Indigenous ethnicity, diabetes type and their interaction.A higher proportion of Indigenous women developed PPH than non-Indigenous women (32% versus 22%; P 0.001). Compared with non-Indigenous women with normoglycemia, risks of PPH for Indigenous women with GDM or T2DM were higher (odds ratio [OR] 1.83, 95% confidence intervals [CI] 1.11-3.02, and OR 1.72, 95% CI 0.99-3.00 after age adjustment, OR 1.84, 95% CI 1.06-3.19, and OR 1.33, 95% CI 0.70-2.54 after adjustment for school education and delivery mode, and OR 1.62, 95% CI 0.95-2.77, and OR 0.99, 95% CI 0.53-1.86 after adjustment for birth weight). Importantly, Indigenous women without hyperglycemia in pregnancy were not at increased risk of PPH.The significantly higher rates of PPH experienced by Indigenous women compared with non-Indigenous women may be explained by a greater effect of GDM among Indigenous women that was only partly accounted for by birth weight.

ObjectiveTo identify factors associated with sight-threatening diabetic macular oedema (STDM) in Indigenous Australians attending an Indigenous primary care clinic in remote Australia.Methods and analysisA cross-sectional study design of retinopathy screening data and routinely-collected clinical data among 236 adult Indigenous participants with type 2 diabetes (35.6% men) set in one Indigenous primary care clinic in remote Australia. The primary outcome variable was STDM assessed from retinal images.ResultsAge (median (range)) was 48 (21–86) years, and known diabetes duration (median (range)) was 8.0 (0–24) years. Prevalence of STDM was high (14.8%) and similar in men and women. STDM was associated with longer diabetes duration (11.7 vs 7.9 years, respectively; p300 mg/mmol) (20.6 vs 5.7%, respectively; p=0.014) and chronic kidney disease (25.7 vs 12.2%, respectively; p=0.035). Some clinical factors differed by sex: anaemia was more prevalent in women. A higher proportion of men were smokers, prescribed statins and had increased albuminuria. Men had higher blood pressure, but lower glycated Haemoglobin A1c (HbA1c) levels and body mass index, than women.ConclusionSTDM prevalence was high and similar in men and women. Markers of renal impairment and longer diabetes duration were associated with STDM in this Indigenous primary care population. Embedded teleretinal screening, known diabetes duration-based risk stratification and targeted interventions may lower the prevalence of STDM in remote Indigenous primary care services.Trial registration numberAustralia and New Zealand Clinical Trials Register: ACTRN 12616000370404.

Aboriginal and Torres Strait Islander holistic health represents the interconnection of social, emotional, spiritual and cultural factors on health and well-being. Social factors (education, employment, housing, transport, food and financial security) are internationally described and recognised as the social determinants of health. The social determinants of health are estimated to contribute to 34% of the overall burden of disease experienced by Aboriginal and Torres Strait Islander people. Primary health care services currently ‘do what it takes’ to address social and emotional well-being needs, including the social determinants of health, and require culturally relevant tools and processes for implementing coordinated and holistic responses. Drawing upon a research-setting pilot program, this manuscript outlines key elements encapsulating a strengths-based approach aimed at addressing Aboriginal and Torres Strait Islander holistic social and emotional well-being. The Cultural Pathways Program is a response to community identified needs, designed and led by Aboriginal and Torres Strait Islander people and informed by holistic views of health. The program aims to identify holistic needs of Aboriginal and Torres Strait Islander people as the starting point to act on the social determinants of health. Facilitators implement strengths-based practice to identify social and cultural needs (e.g. cultural and community connection, food and financial security, housing, mental health, transport), engage in a goal setting process and broker connections with social and health services. An integrated culturally appropriate clinical supervision model enhances delivery of the program through reflective practice and shared decision making. These embedded approaches enable continuous review and improvement from a program and participant perspective. A developmental evaluation underpins program implementation and the proposed culturally relevant elements could be further tailored for delivery within primary health care services as part of routine care to strengthen systematic identification and response to social and emotional well-being needs.

(1) Background: Genomic precision medicine (PM) utilises people’s genomic data to inform the delivery of preventive and therapeutic health care. PM has not been well-established for use with people of Aboriginal and Torres Strait Islander ancestry due to the paucity of genomic data from these communities. We report the development of a new protocol using co-design methods to enhance the potential use of PM for Aboriginal Australians. (2) Methods: This iterative qualitative study consists of five main phases. Phase-I will ensure appropriate governance of the project and establishment of a Project Advisory Committee. Following an initial consultation with the Aboriginal community, Phase-II will invite community members to participate in co-design workshops. In Phase-III, the Chief Investigators will participate in co-design workshops and document generated ideas. The notes shall be analysed thematically in Phase-IV with Aboriginal community representatives, and the summary will be disseminated to the communities. In Phase-V, we will evaluate the co-design process and adapt our protocol for the use in partnership with other communities. (3) Discussion: This study protocol represents a crucial first step to ensure that PM research is relevant and acceptable to Aboriginal Australians. Without fair access to PM, the gap in health outcome between Aboriginal and non-Aboriginal Australians will continue to widen.

BACKGROUND: Diabetes is 3-4 times more prevalent in Indigenous Australians with blood glucose levels often above target range. Once weekly formulations of exenatide(exenatide-LAR) have demonstrated significantly greater improvements in glycaemic management with no increased risk of hypoglycaemia and with reductions in bodyweight but have not been studied in Indigenous Australians. AIMS: To assess the feasibility and metabolic effects of once weekly supervised injection of exenatide-LAR in addition to standard care in Indigenous Australians with type 2 diabetes. METHODS: Two communities in Central Australia with longstanding specialist clinical outreach services were allocated by random coin toss to receive once-weekly exenatide-LAR injection with weekly nurse review and adjustment of medication for 20 weeks (community with exenatide-LAR) or to weekly nurse review in addition to standard care over 20 weeks (community without exenatide-LAR). The primary outcome was the feasibility of an intensive diabetes management model of care with and without weekly supervised exenatide-LAR. Secondary outcomes included change in HbA1c. RESULTS: Thirteen participants from the community with exenatide-LAR and nine participants from the community without exenatide-LAR were analysed. Eighty-five percent of individuals in the community with exenatide-LAR and 67% in the community without exenatide-LAR attended more than half of clinic visits. Median difference in the change in HbA1c from baseline to final visit, adjusted for baseline HbA1c, between the community with exenatide-LAR and the community without exenatide-LAR was -3.1%, 95% CI (-5.80%, -0.38%; P = 0.03). CONCLUSIONS: Weekly exenatide-LAR combined with weekly nurse review demonstrated greater improvements in HbA1c, highlighting its potential for use in remote communities.

High prevalence of chronic and infectious diseases in Indigenous populations is a major public health concern both in global and Australian contexts. Limited research has examined the role of built environments in relation to Indigenous health in remote Australia. This study engaged stakeholders to understand their perceptions of the influence of built environmental factors on chronic and infectious diseases in remote Northern Territory (NT) communities. A preliminary set of 1120 built environmental indicators were systematically identified and classified using an Indigenous Indicator Classification System. The public and environmental health workforce was engaged to consolidate the classified indicators (n = 84), and then sort and rate the consolidated indicators based on their experience with living and working in remote NT communities. Sorting of the indicators resulted in a concept map with nine built environmental domains. Essential services and Facilities for health/safety were the highest ranked domains for both chronic and infectious diseases. Within these domains, adequate housing infrastructure, water supply, drainage system, reliable sewerage and power infrastructure, and access to health services were identified as the most important contributors to the development of these diseases. The findings highlight the features of community environments amenable to public health and social policy actions that could be targeted to help reduce prevalence of chronic and infectious diseases Refereed/Peer-reviewed

IntroductionMainstream Australian mental health services are failing Aboriginal young people. Despite investing resources, improvements in well-being have not materialised. Culturally and age appropriate ways of working are needed to improve service access and responsiveness. This Aboriginal-led study brings Aboriginal Elders, young people and youth mental health service staff together to build relationships to co-design service models and evaluation tools. Currently, three Western Australian youth mental health services in the Perth metropolitan area and two regional services are working with local Elders and young people to improve their capacity for culturally and age appropriate services. Further Western Australian sites will be engaged as part of research translation.Methods and analysisRelationships ground the study, which utilises Indigenous methodologies and participatory action research. This involves Elders, young people and service staff as co-researchers and the application of a decolonising, strengths-based framework to create the conditions for engagement. It foregrounds experiential learning and Aboriginal ways of working to establish relationships and deepen non-Aboriginal co-researchers’ knowledge and understanding of local, place-based cultural practices. Once relationships are developed, co-design workshops occur at each site directed by local Elders and young people. Co-designed evaluation tools will assess any changes to community perceptions of youth mental health services and the enablers and barriers to service engagement.Ethics and disseminationThe study has approval from the Kimberley Aboriginal Health Planning Forum Kimberley Research Subcommittee, the Western Australian Aboriginal Health Ethics Committee, and the Curtin University Human Research Ethics Committee. Transferability of the outcomes across the youth mental health sector will be directed by the co-researchers and is supported through Aboriginal and non-Aboriginal organisations including youth mental health services, peak mental health bodies and consumer groups. Community reports and events, peer-reviewed journal articles, conference presentations and social and mainstream media will aid dissemination.

The use of machine learning methods for the prediction of reaction yield is an emerging area. We demonstrate the applicability of support vector regression (SVR) for predicting reaction yields, using combinatorial data. Molecular descriptors used in regression tasks related to chemical reac?tivity have often been based on time-consuming, computationally demanding quantum chemical calculations, usually density functional theory. Structure-based descriptors (molecular fingerprints and molecular graphs) are quicker and easier to calculate, and are applicable to any molecule. In this study, SVR models built on structure-based descriptors were compared to models built on quantum chemical descriptors. The models were evaluated along the dimension of each reaction component in a set of Buchwald-Hartwig amination reactions. The structure-based SVR models out-performed the quantum chemical SVR models, along the dimension of each reaction compo?nent. The applicability of the models was assessed with respect to similarity to training. Prospec?tive predictions of unseen Buchwald-Hartwig reactions are presented for synthetic assessment, to validate the generalisability of the models, with particular interest along the aryl halide dimension.

Background and Aims: Despite known Indigenous health and socioeconomic disadvantage in countries with a Very High Human Development Index, data on the incidence of stroke in these populations are sparse. With oversight from an Indigenous Advisory Board, we will undertake a systematic review of the incidence of stroke in Indigenous populations of developed countries or regions, with comparisons between Indigenous and non-Indigenous populations of the same region, though not between different Indigenous populations.Methods: Using PubMed, OVID-EMBASE, and Global Health databases, we will examine population-based incidence studies of stroke in Indigenous adult populations of developed countries published 1990-current, without language restriction. Non-peer-reviewed sources, studies including Results: Primary outcomes include crude, age-specific and/or age-standardized incidence of stroke. Secondary outcomes include overall stroke rates, incidence rate ratio and case-fatality. Results will be synthesized in figures and tables, describing data sources, populations, methodology, and findings. Within-population meta-analysis will be performed if, and where, methodologically sound and comparable studies allow this.Conclusion: We will undertake the first systematic review assessing disparities in stroke incidence in Indigenous populations of developed countries. Data outputs will be disseminated to relevant Indigenous stakeholders to inform public health and policy research.

BackgroundDelirium is a distressing, common and serious condition in older people in hospital. Evidence suggests that it could be prevented in about one-third of patients using multicomponent interventions targeting delirium risk factors, but these interventions are not yet routinely available in the NHS.ObjectiveThe objective was to improve delirium prevention for older people admitted to the NHS.DesignProject 1 comprised case studies employing qualitative methods (observation, interviews, workshops) in three NHS hospitals to develop the Prevention of Delirium system of care. Project 2 comprised case studies using mixed methods in five NHS hospitals to test the Prevention of Delirium implementation, feasibility and acceptability, and to modify the Prevention of Delirium system of care. Project 3 comprised a multicentre, cluster randomised, controlled, pragmatic feasibility study in eight hospitals, with embedded economic evaluation, to investigate the potential clinical effectiveness and cost-effectiveness of the Prevention of Delirium system of care, compared with standard care, among older patients admitted to hospital for emergency care. The primary objectives related to gathering information to design a definitive trial. Criteria for progression to a definitive trial were as follows: a minimum of six wards (75%) completing the Prevention of Delirium manual milestone checklist and an overall recruitment rate of at least 10% of the potential recruitment pool.SettingThis study was set in NHS general hospitals.ParticipantsIn project 1, participants were staff, volunteers, and patient and carer representatives. In project 2, participants were staff, volunteers, patients and carers. In project 3, participants were older patients admitted to elderly care and orthopaedic trauma wards.InterventionThe developed intervention (i.e. the Prevention of Delirium system of care).Main outcome measuresFor the feasibility study (project 3), the primary outcome measure was the Confusion Assessment Method. The secondary outcome measures were the Nottingham Extended Activities of Daily Living scale, the Clinical Anxiety Scale and the Geriatric Depression Scale Short Form.ResultsProject 1: understanding of delirium prevention was poor. Drawing on evidence, and working with ward teams, we developed the Prevention of Delirium system of care, which targeted 10 delirium risk factors. This multicomponent intervention incorporated systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Project 2: five out of six wards implemented or partially implemented the Prevention of Delirium intervention. A prominent role for hospital volunteers was intended, but most wards were unable to recruit or sustain the numbers needed. We identified four conditions necessary to implement and deliver the Prevention of Delirium intervention: (1) commitment of senior nurse, (2) a named person to drive implementation forward, (3) dedicated time (1 day per week) of an experienced nurse to lead implementation and (4) adequate ward staffing levels. Overall, the intervention was acceptable to staff, volunteers, patients and carers, and did not increase nursing staff workload. In the light of these findings, the Prevention of Delirium system of care was modified for use in project 3. Project 3: 16 wards in eight hospitals (two wards per hospital) were recruited. Out of 4449 patients screened, 3274 (73.6%) were eligible and 713 were registered, resulting in a recruitment rate of 16.0%. Thirty-three (4.6%) participants withdrew. The screened and registered participants were similar, but some between-treatment group imbalances were noted among those registered to the trial. All eight wards allocated to the intervention group completed the Prevention of Delirium manual milestone checklist and delivered the Prevention of Delirium intervention (median time 18.6 weeks for implementation). Overall, fidelity to the intervention was assessed as being high in two wards, medium in five wards and low in one ward. Of the expected 5645 Confusion Assessment Method delirium assessments, 5065 (89.7%) were completed during the first 10 days of admission. The rates of return of the patient-reported questionnaire booklets were 98.0% at baseline, 81.8% at 30 days and 70.5% at 3 months. The return rate of the EuroQol-5 Dimensions questionnaire was 98.6% at baseline, 77.5% at 1 month and 65.3% at 3 months (94–98% fully completed). The completion rate of the resource use questionnaire was lower (48.7%). The number of people with new-onset delirium at 10 days was 24 (7.0%) in the Prevention of Delirium group and 33 (8.9%) in the control group. Multilevel logistic regression analysis showed that participants in the Prevention of Delirium group had non-significant lower odds of developing delirium (odds ratio 0.68, 95% confidence interval 0.37 to 1.26;p = 0.2225). The average cost of the Prevention of Delirium intervention was estimated as £10.98 per patient and the mean costs for the Prevention of Delirium and usual-care groups were £5332 and £4412, respectively, with negligible between-group differences in quality-adjusted life-years. There was conflicting evidence from the trial- and model-based analyses relating to the cost-effectiveness of the Prevention of Delirium intervention. Given this, and in view of issues with the data (e.g. high levels of missingness), the results from the economic evaluation are highly uncertain. The criteria for continuation to a future definitive randomised controlled trial were met. Such a trial would need to recruit 5200 patients in 26 hospital clusters (200 patients per cluster).ConclusionsThe Prevention of Delirium system of care was successfully developed, and a multicentre feasibility study showed that the intervention is capable of implementation and delivery in routine care, with acceptable intervention fidelity and preliminary estimate of effectiveness.LimitationsA prominent role for volunteers was originally intended in the Prevention of Delirium system of care, but only three of the eight wards allocated to the trial intervention group involved volunteers.Future workThe findings indicate that a definitive multicentre evaluation of the Prevention of Delirium system of care should be designed and conducted to obtain robust estimates of clinical effectiveness and cost-effectiveness.Trial registrationCurrent Controlled Trials ISRCTN28213290 (project 1), ISRCTN65924234 (project 2) and ISRCTN01187372 (project 3).FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 9, No. 4. See the NIHR Journals Library website for further project information.

AIM: There is a wealth of data concerning the health behaviours of Indigenous Australians, but the health behaviours of Indigenous Australians with diabetes are not systematically documented. At the clinical level, understanding a person's health behaviours can help identify and address barriers to diabetes care and promote good clinical outcomes. METHODS: We used a novel survey tool to systematically collect health behaviour data on Smoking, Nutrition, Alcohol consumption, Physical activity and Emotional well-being (SNAPE) from Indigenous Australians with Type 2 diabetes in a remote primary care setting in Alice Springs. RESULTS: At least one of the five surveys in the SNAPE tool was completed by 210 participants: 30% male, mean age 52.6 years (range 22.9 - 87.4). Fifty per cent of men and 23% of women were current smokers (P

Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is NewBackgroundPostoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up.MethodsThis study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method–based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months.ResultsOne hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07–1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72–1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71–2.09).ConclusionsDelirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

Background The Getting it Right study determined the validity, sensitivity, specificity and acceptability of the culturally adapted 9-item Patient Health Questionnaire (aPHQ-9) as a screening tool for depression in Aboriginal and Torres Strait Islander (hereafter referred to as Indigenous) people. In this process evaluation we aimed to explore staff perceptions about whether Getting it Right was conducted per protocol, and if the aPHQ-9 was considered an acceptable and feasible screening tool for depression in primary healthcare. This process evaluation will provide information for clinicians and policy makers about the experiences of staff and patients with Getting it Right and what they thought about using the aPHQ-9. Methods Process evaluation using grounded theory approaches. Semi-structured interviews with primary healthcare staff from services participating in Getting it Right were triangulated with feedback (free-text and elicited) from participants collected during the validation study and field notes. Data were thematically analysed according to the Getting it Right study protocol to identify the acceptability and feasibility of the aPHQ-9. Results Primary healthcare staff (n = 36) and community members (n = 4) from nine of the ten participating Getting it Right services and Indigenous participants (n = 500) from the ten services that took part. Most staff reported that the research was conducted according to the study protocol. Staff from two services reported sometimes recruiting opportunistically (rather than recruiting consecutive patients attending the service as outlined in the main study protocol), when they spoke to patients who they knew from previous interactions, because they perceived their previous relationship may increase the likelihood of patients participating. All Getting it Right participants responded to at least six of the seven feedback questions and 20% provided free-text feedback. Most staff said they would use the aPHQ-9 and most participants said that the questions were easy to understand (87%), the response categories made sense (89%) and that they felt comfortable answering the questions (91%). Conclusion Getting it Right was predominantly conducted according to the study protocol. The aPHQ-9, the first culturally adapted, nationally validated, freely available depression screening tool for use by Indigenous people, appears to be acceptable and feasible to use. Trial registration Australian New Zealand Clinical Trial Registry ANZCTR12614000705684, 03/07/2014.

Objectives\ud \ud To determine the validity, sensitivity, specificity and acceptability of the culturally adapted nine‐item Patient Health Questionnaire (aPHQ‐9) as a screening tool for depression in Aboriginal and Torres Strait Islander people.\ud \ud Design\ud \ud Prospective observational validation study, 25 March 2015 – 2 November 2016.\ud \ud Setting, participants\ud \ud 500 adults (18 years or older) who identified as Aboriginal or Torres Strait Islander people and attended one of ten primary health care services or service events in urban, rural and remote Australia that predominantly serve Indigenous Australians, and were able to communicate sufficiently to respond to questionnaire and interview questions.\ud \ud \ud Main outcome measures\ud \ud Criterion validity of the aPHQ‐9, with the depression module of the Mini‐International Neuropsychiatric Interview (MINI) 6.0.0 as the criterion standard.\ud \ud \ud Results\ud \ud 108 of 500 participants (22%; 95% CI, 18–25%) had a current episode of major depression according to the MINI criterion. The sensitivity of the aPHQ‐9 algorithm for diagnosing a current major depressive episode was 54% (95% CI, 40–68%), its specificity was 91% (95% CI, 88–94%), with a positive predictive value of 64%. For screening for a current major depressive episode, the area under the receiver operator characteristic curve was 0.88 (95% CI, 0.85–0.92); with a cut‐point of 10 points its sensitivity was 84% (95% CI, 74–91%) and its specificity 77% (95% CI, 71–83%). The aPHQ‐9 was deemed acceptable by more than 80% of participants.\ud \ud \ud Conclusions\ud \ud Indigenous Australians found the aPHQ‐9 acceptable as a screening tool for depression. Applying a cut‐point of 10 points, the performance characteristics of the aPHQ were good.

Summary Background Rapid demographic, epidemiological, and nutritional transitons have brought a pressing need to track progress in adolescent health. Here, we present country-level estimates of 12 headline indicators from the Lancet Commission on adolescent health and wellbeing, from 1990 to 2016. Methods Indicators included those of health outcomes (disability-adjusted life-years [DALYs] due to communicable, maternal, and nutritional diseases; injuries; and non-communicable diseases); health risks (tobacco smoking, binge drinking, overweight, and anaemia); and social determinants of health (adolescent fertility; completion of secondary education; not in education, employment, or training [NEET]; child marriage; and demand for contraception satisfied with modern methods). We drew data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, International Labour Organisation, household surveys, and the Barro-Lee education dataset. Findings From 1990 to 2016, remarkable shifts in adolescent health occurred. A decrease in disease burden in many countries has been offset by population growth in countries with the poorest adolescent health profiles. Compared with 1990, an additional 250 million adolescents were living in multi-burden countries in 2016, where they face a heavy and complex burden of disease. The rapidity of nutritional transition is evident from the 324·1 million (18%) of 1·8 billion adolescents globally who were overweight or obese in 2016, an increase of 176·9 million compared with 1990, and the 430·7 million (24%) who had anaemia in 2016, an increase of 74·2 million compared with 1990. Child marriage remains common, with an estimated 66 million women aged 20–24 years married before age 18 years. Although gender-parity in secondary school completion exists globally, prevalence of NEET remains high for young women in multi-burden countries, suggesting few opportunities to enter the workforce in these settings. Interpretation Although disease burden has fallen in many settings, demographic shifts have heightened global inequalities. Global disease burden has changed little since 1990 and the prevalence of many adolescent health risks have increased. Health, education, and legal systems have not kept pace with shifting adolescent needs and demographic changes. Gender inequity remains a powerful driver of poor adolescent health in many countries. Funding Australian National Health and Medical Research Council, and the Bill & Melinda Gates Foundation.

In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10-fold higher in Indigenous than non-Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register.The study included women with gestational diabetes (GDM), newly diagnosed diabetes in pregnancy (DIP), or pre-existing T2D from 2012 to 2016. Data were analyzed for metformin use in the third trimester. Regression models were adjusted for maternal age, body mass index, parity, and insulin use.Of 1649 pregnancies, 814 (49.4%) were to Indigenous women, of whom 234 (28.7%) had T2D (vs 4.6% non-Indigenous women; P 0.001). Metformin use was high in Indigenous women (84%-90% T2D, 42%-48% GDM/DIP) and increased over time in non-Indigenous women (43%-100% T2D, 14%-35% GDM/DIP). Among Indigenous women with GDM/DIP, there were no significant differences between groups with and without metformin in cesarean section (51% vs 39%; adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.87-1.81), large for gestational age (24% vs 13%; aOR 1.5, 95% CI 0.9-2.5), or serious neonatal adverse events (9.4% vs 5.9%; aOR 1.32, 95% CI 0.68-2.57). Metformin use was independently associated with earlier gestational age (37.7 vs 38.5 weeks), but the risk did not remain independently higher after exclusion of women managed with medical nutrition therapy alone, and the increase in births37 weeks was not significant on multivariate analysis.We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy.摘要: 背景 在澳大利亚北部地区, 原住民母亲的婴儿出生率占33%, 她们妊娠期间出现高血糖的风险很高。原住民母亲在妊娠期间的2型糖尿病(T2D)患病率与非原住民澳大利亚母亲相比较要高10倍, 并且经常使用二甲双胍治疗。我们利用临床登记表数据评估了妊娠期间使用二甲双胍治疗与出生结果之间的关系。 方法 这项研究从2012至2016年纳入了妊娠糖尿病(gestational diabetes, GDM)、妊娠期新诊断糖尿病(newly diagnosed diabetes in pregnancy, DIP)以及既往已经存在T2D的妇女。对妊娠晚期使用二甲双胍的数据进行了分析。根据母亲年龄、体重指数、产次以及胰岛素使用情况校正了回归模型。 结果 在1649名孕妇中有814名(49.4%)为原住民妇女, 其中234名(28.7%)为T2D(非原住民妇女T2D比例为4.6%；P 0.001)。原住民妇女的二甲双胍使用率更高(在T2D中为84%-90%, 在GDM/DIP中为42%-48%), 并且在非原住民妇女中随着时间的推移使用率在上升(在T2D中为43%-100%, 在GDM/DIP中为14%-35%)。在合并GDM/DIP的原住民妇女中, 使用二甲双胍治疗组与不使用二甲双胍治疗组之间的剖宫产率(分别为51%与39%; 校正后的odds ratio [aOR]为1.25, 95%置信区间[CI]为0.87-1.81)、出现大胎龄率(分别为24%与13%；aOR为1.5, 95% CI为0.9-2.5)、新生儿出现严重不良事件率(分别为9.4%与5.9%；aOR为1.32, 95% CI为0.68-2.57)都没有显著性差异。使用二甲双胍治疗与胎龄更小(分别为37.7与38.5周)独立相关, 但是将单独接受药物营养治疗的妇女排除之后, 这种风险没有独立地处于较高的水平, 并且多变量分析显示37周的出生率并没有显著地升高。 结论 我们没有发现任何与妊娠期间高血糖妇女使用二甲双胍治疗出现不良结果相关的明确证据。.

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Despite advancements in prevention and treatment, sudden cardiac death (SCD) remains a leading cause of mortality and is responsible for approximately half of all deaths from cardiovascular disease. Outcomes continue to remain poor following a sudden cardiac arrest, with most individuals not surviving. Although coronary heart disease remains the dominant underlying condition, our understanding of SCD is improving through greater knowledge of clinical risk factors, cardiomyopathies, and primary arrhythmic disorders. However, despite a growing wealth of information from studies in North America, Europe, and Japan, data from other global regions (and particularly from low-and middle-income countries) remains scarce. Refereed/Peer-reviewed

Background: The postpartum period is a critical time to improve health outcomes for Aboriginal women, particularly for those who have chronic conditions. Aims: To assess enhanced support methods (for women following diabetes in pregnancy (DIP)) to improve completion rates of recommended postpartum health checks. Materials and Methods: Fifty-three Aboriginal women in the Northern Territory (NT) were contacted in the postpartum period to encourage medical check-ups.Messages were delivered through phone (call or text messages) or other methods (Facebook or email). The primary outcome was postpartum blood glucose testing (oral glucose tolerance testing (OGTT), random or fasting glucose and HbA1c). Results: Establishing contact with women was difficult. Of 137 messages sent to52 women, 22 responded (42%). Phone was the most common contact method with successful contact made from 16 of 119 (13%) attempts. Rates of postpartum OGTT completion were higher in the group successfully contacted (32% vs 7%). However, for any postpartum glucose testing (including OGTT and HbA1c) rates were 25 of 42 (60%) and neither success in making contact nor the contact method was associated with higher rates. Conclusions: The small sample size limits our conclusions; however, results highlight that engaging remote women postpartum is difficult. While rates of postpartum OGTT completion differed according to successful contacts, rates of any postpartum blood glucose testing did not. Further research is needed to explore feasible intervention methods to improve postpartum screening after a pregnancy complicated by diabetes. Refereed/Peer-reviewed

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.1668F is a founder variant among Ashkenazi Jews (allele frequency of -.2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function.

Background Associations between kidney disease and periodontal disease are not well documented among Aboriginal people of Australia. The purpose of this investigation was to report and compare demographic, oral health, anthropometric and systemic health status of Aboriginal Australians with kidney disease and to compare against relevant Aboriginal Australians and Australian population estimates. This provides much needed evidence to inform dental health service provision policies for Aboriginal Australians with kidney disease. Methods Sample frequencies and means were assessed in adults represented in six datasets including: (1) 102 Aboriginal Australians with kidney disease residing in Central Australia who participated in a detailed oral health assessment; (2) 312 Aboriginal participants of the Northern Territory’s PerioCardio study; (3) weighted estimates from 4775 participants from Australia’s National Survey of Adult Oral Health (NSAOH); (4) Australian 2016 Census (all Australians); (5) National Health Survey 2017–2018 (all Australians) and; (6) Australian Health Survey: Biomedical Results for Chronic Diseases, 2011–2012 (all Australians). Oral health status was described by periodontal disease and experience of dental caries (tooth decay). Statistically significant differences were determined via non-overlapping 95% confidence intervals. Results Aboriginal Australians with kidney disease were significantly older, less likely to have a tertiary qualification or be employed compared with both PerioCardio study counterparts and NSAOH participants. Severe periodontitis was found in 54.3% of Aboriginal Australians with kidney disease, almost 20 times the 2.8% reported in NSAOH. A higher proportion of Aboriginal Australians with kidney disease had teeth with untreated caries and fewer dental restorations when compared to NSAOH participants. The extent of periodontal attachment loss and periodontal pocketing among Aboriginal Australians with kidney disease (51.0%, 21.4% respectively) was several magnitudes greater than PerioCardio study (22.0%, 12.3% respectively) and NSAOH (5.4%, 1.3% respectively) estimates. Conclusions Aboriginal Australians with kidney disease exhibited more indicators of poorer oral health than both the general Australian population and a general Aboriginal population from Australia’s Northern Territory. It is imperative that management of oral health among Aboriginal Australians with kidney disease be included as part of their ongoing medical care.

Māori and Pacific women in New Zealand and Aboriginal and Torres Strait Islander women in Australia are recognised as nurturers and leaders within their families and communities. However, women’s wellbeing, and that of their communities, are affected by a high burden of cardiovascular disease experienced at a younger age than women from other ethnic groups. There has been little focus on the cardiovascular outcomes and strategies to address heart health inequities among Māori, Pacific, Aboriginal and Torres Strait Islander women. The factors contributing to these inequities are complex and interrelated but include differences in exposure to risk and protective factors, rates of multi-morbidity, and substantial gaps within the health system, which include barriers to culturally responsive, timely and appropriate cardiovascular care. Evidence demonstrates critical treatment gaps across the continuum of risk and disease, including assessment and management of cardiovascular risk in young women and time-critical access to and receipt of acute services. Cardiovascular disease in women impacts not only the individual, but their family and community, and the burden of living with disease limits women’s capacity to fulfil their roles and responsibilities which support and sustain families and communities. Our response must draw on the strengths of Māori, Pacific, Aboriginal and Torres Strait Islander women, acknowledge health and wellbeing holistically, address the health and social needs of individuals, families and communities, and recognise that Indigenous women in New Zealand, Australia and across the Pacific must be involved in the design, development and implementation of solutions affecting their own health. Refereed/Peer-reviewed

Background: Aboriginal and Torres Strait Islander (hereinafter respectfully termed Aboriginal)people have a greater incidence of stroke at a younger age than non-Indigenous people in Australia. The needs and preferences of Aboriginal people for rehabilitation and longer-term support remain largely unknown. Objectives: To identify the long-term rehabilitation needs of Aboriginal people who have a stroke, from the perspectives of Aboriginal persons with stroke and health care providers. Methods: Aboriginal people who had experienced stroke in the previous three years were interviewed to obtain their experiences of rehabilitation care. Health professionals who provided care in each of six designated hospitals and nearby community health sites were involved in focus groups and individual interviews. Information obtained was thematically analyzed separately for Aboriginal people with stroke and health professionals, and compared using Nvivo. Results: Among six Aboriginal people with stroke and 78 healthcare providers, four main themes emerged: the importance of family; variable access to services; the impact of stroke on Aboriginal peoples’ lives; and making positive choices. Communication and involvement of family was highlighted as essential for a shared understanding, particularly when making decisions about participating in short and long-term rehabilitation. Co–morbidities, conflicting priorities, and inadequate or inflexible services and transport compounded issues with changing life roles. Stories of resilience were also shared. Conclusions: Aboriginal people report making positive lifestyle changes, but experience significant unmet rehabilitation needs. Addressing issues of communication, advocacy and flexible delivery should improve some of the shortfalls in service provision, particularly in regional and remote areas. Refereed/Peer-reviewed

Background: Aboriginal and Torres Strait Islander peoples’ perspectives of health and cultural wellbeing encapsulate the spiritual, social and environmental health of individuals, their communities and country. Strategies designed to reduce the cardiovascular burden of Aboriginal and Torres Strait Islander people often fail to consider their unique knowledge and worldview. Methods: This adapted, grounded theory study sought to explore Aboriginal women’s views of cardiovascular protective and risk factors. Results: Twenty-eight (28) women from five women’s groups across Central and South Australia participated. Women distinguished the heart as core to their spiritual and physical wellbeing. Women identified six attributes that keep a woman’s heart strong, four that can make the heart sick, and eight socio-ecological factors which affect a woman’s capacity to care for their heart. Women described having a healthy heart when able to identify as Aboriginal women, being connected to family and community, having a healthy life and body, and being engaged in their health and health care. Conclusions: There are gaps in the provision of cardiovascular risk assessment and management, gaps in the cultural safety of primary health care services, and gaps in the communication of the sex-specific warning signs of a heart attack, all of which must be addressed. Refereed/Peer-reviewed

A molecular tagging method for velocity measurements in reacting environments such as propulsion devices and high-temperature combustion-assisted wind tunnels is described. The method employs a femtosecond (write) laser to photodissociate H 2 O , a common combustion product, into a locally high concentration of OH radicals. These radicals are tracked by planar laser-induced fluorescence (PLIF) from the A 2 Σ − X 2 Π (1–0) vibrational band excited by a time-delayed 284 nm (read) laser sheet. As a variant of hydroxyl tagging velocimetry, the source laser can also be used to dissociate nitrogen for femtosecond laser electronic excitation tagging velocimetry to mark the time-zero location of the write laser for velocimetry in non-reacting regions using the same imaging system without OH PLIF. The OH tracer lifetime is studied in a hydrogen-air Hencken burner operating at Φ = 0.5 − 1.8 to evaluate the tracking capability for velocimetry over a range of conditions. Effects of changing read laser wavelength, excitation energy, and influence of background flame emission are also studied. The data processing methodology and results are described for tracking displacements with 9–25 µm uncertainty in a hydrogen diffusion flame. This method presents several advantages in operational convenience and availability of laser sources, and it provides an avenue for improvements in the repetition rate, precision, and applicability over previously demonstrated hydroxyl tagging schemes.

BACKGROUND The Northern Territory (NT) has a long history of heavy alcohol consumption with a correspondingly high attributable morbidity and mortality. AIMS To describe the number of admissions to intensive care associated with alcohol misuse. METHODS This is a prospective case-control study including all admissions to NT intensive care units (ICU) between 1 July 2018 and 30 June 2019. Characteristics and outcomes of patients who had an admission associated with alcohol misuse (a composite measure of acute and/or chronic misuse) were compared to those who did not. Primary outcome was the number of admissions associated with alcohol misuse. Secondary outcomes included measures of resource use (length of stay (LoS), need for mechanical ventilation) and mortality adjusted for illness severity. RESULTS Over the sampling period there were 1664 admissions. After exclusions, 1471 admissions were analysed, of which 307 (21%) were associated with alcohol misuse. Acute or chronic misuse was associated with 3.7% and 12.1% of admissions respectively, while 5.1% met criteria for both. Admissions associated with alcohol misuse more frequently required ventilation (38.4% vs 20.7%, P

Summary Introduction Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, with significant potential for positive impact on public health and healthcare savings. New clinical practice recommendations are presented in an abridged guidance to assist practitioners in enhancing the care of all patients with FH. Main recommendations Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. There is a key role for general practitioners (GPs) working in collaboration with specialists with expertise in lipidology. Advice is given on genetic and cholesterol testing and risk notification of biological relatives undergoing cascade testing for FH; all healthcare professionals should develop skills in genomic medicine. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors, and appropriate use of low-density lipoprotein (LDL)-cholesterol lowering therapies, including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Recommendations on service design are provided in the full guidance. Potential impact on care of FH These recommendations need to be utilised using judicious clinical judgement and shared decision making with patients and families. Models of care need to be adapted to both local and regional needs and resources. In Australia new government funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of these recommendations. A broad implementation science strategy is, however, required to ensure that the guidance translates into benefit for all families with FH.

Background Indigenous populations globally are continually striving for better health and wellbeing due to experiencing significant health and social inequities. The social determinants of health are important contributors to health outcomes. Comprehensive primary health care that is governed and delivered by Indigenous people extends beyond the biomedical model of care to address the social determinants of health. Aboriginal Community Controlled Health Organisations (ACCHOs) are known to provide culturally informed, holistic health services that directly and indirectly address the social determinants of health. The range and extent of their activities in addressing the social determinants of health, however, is not well documented. Methods The most recent ACCHO annual reports were retrieved online or by direct correspondence. For coding consistency, a dictionary informed by the World Health Organization’s Conceptual Framework for Action on the Social Determinants of Health was developed. A document and textual analysis of reports coded ACCHO activities and the determinants of health they addressed, including intermediary determinants, socio-economic position and/or socio-political context. Summary statistics were reported. Representative quotes illustrating the unique nature of ACCHO service provision in addressing the social determinants of health were used to contextualise the quantitative findings. Results Sixty-seven annual reports were collected between 2017 and 2018. Programs were delivered to population groups across the life span. Fifty three percent of reports identified programs that included work at the socio-political level and all annual reports described working to improve socioeconomic position and intermediary determinants of health through their activities. Culture had a strong presence in program delivery and building social cohesion and social capital emerged as themes. Conclusions This study provides evidence of the considerable efforts of the ACCHO sector, as a primary health care provider, in addressing the social determinants of health and health inequity experienced by Indigenous communities. For the Aboriginal and Torres Strait Islander population, ACCHOs not only have an essential role in addressing immediate healthcare needs but also invest in driving change in the more entrenched structural determinants of health. These are important actions that are likely to have an accumulative positive effect in closing the gap towards health equity.

Aims To describe the effect of alcohol policy on the incidence of intensive care unit (ICU) admissions associated with hazardous and harmful alcohol use in the Northern Territory (NT) of Australia DESIGN, SETTING AND PARTICIPANTS: Before and after analysis of admissions to NT ICUs between April 2018 and September 2019, extending on both a descriptive study describing hazardous and harmful alcohol use and single-centre analyses of harm minimization policies. After exclusions, 2281 (83%) admissions were analysed, 20.3% of which were associated with hazardous and harmful alcohol use. Measurements Primary outcome was the incidence of admissions associated with hazardous and harmful alcohol use in the 5 months preceding (baseline period) the introduction of new alcohol policies [full-time stationing of Police Auxiliary Liquor Inspectors (PALIs) and minimum unit price (MUP)] compared with 12 months (post-intervention) following. Secondary outcomes included measures of resource use [length of stay (LoS), need for mechanical ventilation] and mortality, stratified by site. Findings Overall, there was a 4.5% [95% confidence interval (CI) = 0.8-8.2%] absolute risk reduction between the time-periods (95% CI = 23.4 versus 18.9% for baseline and post-intervention, respectively, P = 0.01), predominantly due to a reduction in admissions associated with acute misuse (2.3%, 95% CI = -0.2 to 4.9% risk reduction, P = 0.06). There were regional differences, with a more marked relative risk reduction observed in Central Australia compared with the city of Darwin (27.0 versus 16.7% relative risk reduction, respectively). Conclusions Introduction of new alcohol harm minimization policies in the Northern Territory of Australia appears to have reduced the number of intensive care unit admissions associated with hazardous and harmful alcohol use. Strength of effect varies by geographical region and chronicity of hazardous and harmful alcohol use.

Background Rheumatic heart disease (RHD) affects over 40 million people globally who are predominantly young and from impoverished communities. The barriers to valvular intervention are complex and contribute to the high morbidity and mortality associated with RHD. The rates of guideline indicated intervention in patients with significant RHD have not yet been reported. Methods From 2007 to 2017, we used the Australian Northern Territory Cardiac Database to identify patients with RHD who fulfilled at least one ESC/EACTS guideline indication for mitral valve intervention. Baseline clinical status, comorbidities, echocardiographic parameters, indication for intervention, referral and any interventions were recorded. Results 154 patients (mean age 38.5 ± 14.6, 66.1% female) were identified as having a class I or IIa indication for invasive management. Symptoms, atrial fibrillation and pulmonary hypertension were the most common indications for surgery (74.5%, 48.1%, 40.9%). From the onset of a guideline indication the actuarial rates of accepted referral and intervention within two-years were 66.0% ± 4.0% and 53.1% ± 4.4% respectively. Of those who were referred and accepted for intervention, 86% received it within 2 years. The rates of accepted referral for patients with class I indications were 72.5% ± 4.2% while class IIa indications were 42.5% ± 9.0% (p Conclusions Approximately half of Aboriginal patients with significant rheumatic mitral valve disease who met ESC/EACTS guideline indications for intervention received surgery or valvuloplasty within two-years. A significant difference in referral rates was found between Class I and Class IIa indications for valvular intervention.

Objective Periodontal disease is associated with chronic kidney disease (CKD), with both conditions being highly prevalent among Australia’s Aboriginal population. This paper reflects on the lessons learned following implementation of a periodontal intervention in the Central Australian region of the Northern Territory among Aboriginal adults with CKD. Results Between Oct 2016 and May 2019, research staff recruited 102 eligible participants. This was far below the anticipated recruitment rate. The challenges faced, and lessons learned, were conceptualised into five specific domains. These included: (1) insufficient engagement with the Aboriginal community and Aboriginal community-controlled organisations; (2) an under-appreciation of the existing and competing patient commitments with respect to general health and wellbeing, and medical treatment to enable all study commitments; (3) most study staff employed from outside the region; (4) potential participants not having the required number of teeth; (5) invasive intervention that involved travel to, and time at, a dental clinic. A more feasible research model, which addresses the divergent needs of participants, communities and service partners is required. This type of approach, with sufficient time and resourcing to ensure ongoing engagement, partnership and collaboration in co-design throughout the conduct of research, challenges current models of competitive, national research funding.