Publications by authors named "Alex Brown"

488 Publications

Co-Designing Health Service Evaluation Tools That Foreground First Nation Worldviews for Better Mental Health and Wellbeing Outcomes.

Int J Environ Res Public Health 2021 08 13;18(16). Epub 2021 Aug 13.

School of Allied Health, Curtin University, Bentley, Perth 6102, Australia.

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.
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http://dx.doi.org/10.3390/ijerph18168555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394671PMC
August 2021

Hidden Spin-Isospin Exchange Symmetry.

Phys Rev Lett 2021 Aug;127(6):062501

Helmholtz-Institut für Strahlen- und Kernphysik and Bethe Center for Theoretical Physics, Universität Bonn, D-53115 Bonn, Germany.

The strong interactions among nucleons have an approximate spin-isospin exchange symmetry that arises from the properties of quantum chromodynamics in the limit of many colors, N_{c}. However this large-N_{c} symmetry is well hidden and reveals itself only when averaging over intrinsic spin orientations. Furthermore, the symmetry is obscured unless the momentum resolution scale is close to an optimal scale that we call Λ_{large-N_{c}}. We show that the large-N_{c} derivation requires a momentum resolution scale of Λ_{large-N_{c}}∼500  MeV. We derive a set of spin-isospin exchange sum rules and discuss implications for the spectrum of ^{30}P and applications to nuclear forces, nuclear structure calculations, and three-nucleon interactions.
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http://dx.doi.org/10.1103/PhysRevLett.127.062501DOI Listing
August 2021

The more things change, the more they stay the same: enduring inequity in Indigenous health.

Authors:
Alex Brown

Aust Health Rev 2021 Aug;45(4):395-396

South Australian Health and Medical Research Institute, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia. Email:

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http://dx.doi.org/10.1071/AHv45n4_ED1DOI Listing
August 2021

Improving systems of prenatal and postpartum care for hyperglycemia in pregnancy: A process evaluation.

Int J Gynaecol Obstet 2021 Jul 31. Epub 2021 Jul 31.

Division of Wellbeing and Preventable Chronic Disease, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.

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.
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http://dx.doi.org/10.1002/ijgo.13850DOI Listing
July 2021

Gestational diabetes is associated with postpartum hemorrhage in Indigenous Australian women in the PANDORA study: A prospective cohort.

Int J Gynaecol Obstet 2021 Jul 30. Epub 2021 Jul 30.

Wellbeing and Preventable Chronic Disease Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1002/ijgo.13846DOI Listing
July 2021

Associations with sight-threatening diabetic macular oedema among Indigenous adults with type 2 diabetes attending an Indigenous primary care clinic in remote Australia: a Centre of Research Excellence in Diabetic Retinopathy and Telehealth Eye and Associated Medical Services Network study.

BMJ Open Ophthalmol 2021 1;6(1):e000559. Epub 2021 Jul 1.

Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

Objective: To identify factors associated with sight-threatening diabetic macular oedema (STDM) in Indigenous Australians attending an Indigenous primary care clinic in remote Australia.

Methods And Analysis: A 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.

Results: Age (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; p<0.001) and markers of renal impairment: abnormal estimated Glomerular Filtration Rate (eGFR) (62.9 vs 38.3%, respectively; p=0.007), severe macroalbuminuria (>300 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.

Conclusion: STDM 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 Number: Australia and New Zealand Clinical Trials Register: ACTRN 12616000370404.
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http://dx.doi.org/10.1136/bmjophth-2020-000559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252880PMC
July 2021

A Pathway to Precision Medicine for Aboriginal Australians: A Study Protocol.

Methods Protoc 2021 Jun 21;4(2). Epub 2021 Jun 21.

Poche Centre for Indigenous Health, The University of Sydney, Camperdown, NSW 2050, Australia.

(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.
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http://dx.doi.org/10.3390/mps4020042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293410PMC
June 2021

Strengthening approaches to respond to the social and emotional well-being needs of Aboriginal and Torres Strait Islander people: the Cultural Pathways Program.

Prim Health Care Res Dev 2021 06 29;22:e35. Epub 2021 Jun 29.

Wardliparingga Aboriginal Health Equity, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia.

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.
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http://dx.doi.org/10.1017/S1463423621000402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278791PMC
June 2021

Perspectives on rehabilitation for Aboriginal people with stroke: a qualitative study.

Top Stroke Rehabil 2021 Jun 28:1-15. Epub 2021 Jun 28.

Stroke and Ageing Research Group, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia.

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.
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http://dx.doi.org/10.1080/10749357.2021.1911771DOI Listing
June 2021

Global epidemiology of valvular heart disease.

Nat Rev Cardiol 2021 Jun 25. Epub 2021 Jun 25.

Department of Cardiology, St Thomas' Hospital, London, UK.

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.
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http://dx.doi.org/10.1038/s41569-021-00570-zDOI Listing
June 2021

Recovery of high specific activity molybdenum-99 from accelerator-induced fission on low-enriched uranium for technetium-99m generators.

Sci Rep 2021 Jun 24;11(1):13292. Epub 2021 Jun 24.

Chemical and Fuel Cycle Technologies, Argonne National Laboratory, 9700 S Cass Ave, Lemont, IL, 60439, USA.

A new process was developed to recover high specific activity (no carrier added) Mo from electron-accelerator irradiated UO or uranyl sulfate targets. The process leverages a novel solvent extraction scheme to recover Mo using di(2-ethylhexyl) phosphoric acid following uranium and transuranics removal with tri-n-butyl phosphate. An anion-exchange concentration column step provides a final purification, generating pure Mo intended for making Mo/Tc generators. The process was demonstrated with irradiated uranium targets resulting in more than 95% Mo recovery and without presence of fission products or actinides in the product.
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http://dx.doi.org/10.1038/s41598-021-92704-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225826PMC
June 2021

Feasibility of once weekly exenatide-LAR and enhanced diabetes care in Indigenous Australians with type 2 diabetes (Long-acting-Once-Weekly-Exenatide laR-SUGAR, 'Lower SUGAR' study).

Intern Med J 2021 Sep;51(9):1463-1472

Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

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.
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http://dx.doi.org/10.1111/imj.15428DOI Listing
September 2021

Cohort profile: indigenous human papillomavirus and oropharyngeal squamous cell carcinoma study - a prospective longitudinal cohort.

BMJ Open 2021 06 3;11(6):e046928. Epub 2021 Jun 3.

Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, New South Wales, Australia.

Purpose: Our aims are to: (1) estimate prevalence, incidence, clearance and persistence of oral human papillomavirus (HPV) infection among Indigenous Australians; (2) identify risk factors associated with oropharyngeal squamous cell carcinoma (OPSCC)-related HPV types (HPV 16 or 18); (3) develop HPV-related health state valuations and; (4) determine the impact on OPSCC and cervical cancers, and the cost-effectiveness of extending publicly-funded HPV vaccination among Indigenous Australians.

Participants: Participants were recruited from February 2018 to January 2019. Twelve-month follow-up occurred from March 2019 to March 2020. Participants provided socio-demographic characteristics, health-related behaviours including tobacco and alcohol use and sexual history. Health state preferences in regard to HPV vaccination, knowledge regarding HPV infection, OPSCC and cervical cancer were collected using a two-stage standard gamble approach. Participants provided saliva samples and DNA for microbial genotyping was extracted.

Findings To Date: Of the 910 participants who were positive for β-globin at baseline, 35% had any oral HPV infection. The most prevalent HPV types were 13 or 32 (Heck's disease; 23%). The second most prevalent types were associated with OPSCC (HPV 16 or 18; 3.3%). Of the 645 participants who were positive for β-globin at 12-month follow-up, 43% had any HPV infection. Of these, 33% were HPV types 13 or 32 and 2.5% were HPV 16 or 18. Some 588 participants had β-globin positive oral samples at baseline and 12-month follow-up. The prevalence of any oral HPV infection increased from 34% at baseline to 44% at 12-month follow-up; due to increases in HPV types 13 or 32 (20% at baseline and 34% at 12-month follow-up).

Future Plans: Further funding will be sought to continue follow-up of this cohort, and to include (after a full medical history) a thorough clinical examination of the external head and neck; a complete oral examination and examination of the oropharynx. Blood tests for early stage OPSCC will also be undertaken.
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http://dx.doi.org/10.1136/bmjopen-2020-046928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183277PMC
June 2021

Prioritizing Built Environmental Factors to Tackle Chronic and Infectious Diseases in Remote Northern Territory (NT) Communities of Australia: A Concept Mapping Study.

Int J Environ Res Public Health 2021 05 13;18(10). Epub 2021 May 13.

School of Health Sciences, University of South Australia, Adelaide, SA 5001, Australia.

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 ( = 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.
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http://dx.doi.org/10.3390/ijerph18105178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152969PMC
May 2021

Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches.

Acta Neuropathol Commun 2021 05 31;9(1):101. Epub 2021 May 31.

Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, ND2-4044195, USA.

Glioblastoma (GBM) displays marked cellular and metabolic heterogeneity that varies among cellular microenvironments within a tumor. Metabolic targeting has long been advocated as a therapy against many tumors including GBM, but how lipid metabolism is altered to suit different microenvironmental conditions and whether cancer stem cells (CSCs) have altered lipid metabolism are outstanding questions in the field. We interrogated gene expression in separate microenvironments of GBM organoid models that mimic the transition between nutrient-rich and nutrient-poor pseudopalisading/perinecrotic tumor zones using spatial-capture RNA-sequencing. We revealed a striking difference in lipid processing gene expression and total lipid content between diverse cell populations from the same patient, with lipid enrichment in hypoxic organoid cores and also in perinecrotic and pseudopalisading regions of primary patient tumors. This was accompanied by regionally restricted upregulation of hypoxia-inducible lipid droplet-associated (HILPDA) gene expression in organoid cores and pseudopalisading regions of clinical GBM specimens, but not lower-grade brain tumors. CSCs have low lipid droplet accumulation compared to non-CSCs in organoid models and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. Targeted lipidomic analysis of multiple patient-derived models revealed a significant shift in lipid metabolism between GBM CSCs and non-CSCs, suggesting that lipid levels may not be simply a product of the microenvironment but also may be a reflection of cellular state. CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs, but had significantly increased polyunsaturated fatty acid production due to high fatty acid desaturase (FADS1/2) expression which was essential to maintain CSC viability and self-renewal. Our data demonstrate spatially and hierarchically distinct lipid metabolism phenotypes occur clinically in the majority of patients, can be recapitulated in laboratory models, and may represent therapeutic targets for GBM.
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http://dx.doi.org/10.1186/s40478-021-01205-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166002PMC
May 2021

Our journey, our story: a study protocol for the evaluation of a co-design framework to improve services for Aboriginal youth mental health and well-being.

BMJ Open 2021 05 19;11(5):e042981. Epub 2021 May 19.

School of Allied Health, Curtin University, Perth, Western Australia, Australia.

Introduction: Mainstream 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 Analysis: Relationships 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 Dissemination: The 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.
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http://dx.doi.org/10.1136/bmjopen-2020-042981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137218PMC
May 2021

The Incidence of Stroke in Indigenous Populations of Countries With a Very High Human Development Index: A Systematic Review Protocol.

Front Neurol 2021 22;12:661570. Epub 2021 Apr 22.

School of Population and Global Health, University of Western Australia, Perth, WA, Australia.

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. 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 <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, with standard data extracted for all studies included. Quality assessment will include Sudlow and Warlow's criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and the CONSIDER checklist for Indigenous research. 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. 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.
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http://dx.doi.org/10.3389/fneur.2021.661570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100239PMC
April 2021

Circadian disruption by short light exposure and a high energy diet impairs glucose tolerance and increases cardiac fibrosis in Psammomys obesus.

Sci Rep 2021 May 6;11(1):9673. Epub 2021 May 6.

South Australian Health & Medical Research Institute, Adelaide, Australia.

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 < 0.05) and HE (44%, P < 0.05) diets, when compared to groups with neutral photoperiod exposure. Short photoperiod exposure caused elevations in mRNA levels of hypertrophy gene 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.
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http://dx.doi.org/10.1038/s41598-021-89191-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102519PMC
May 2021

Enablers and barriers to primary healthcare for Aboriginal and Torres Strait Islander adolescents: study protocol for participatory mixed-methods research that builds on WHO global standards.

BMJ Open 2021 04 29;11(4):e046459. Epub 2021 Apr 29.

Wardliparingga Aboriginal Health Equity Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia

Introduction: One-third of Australia's Aboriginal and Torres Strait Islander population are adolescents. Recent data highlight their health needs are substantial and poorly met by existing services. To design effective models of primary healthcare, we need to understand the enablers and barriers to care for Aboriginal and Torres Strait Islander adolescents, the focus of this study.

Methods And Analysis: This protocol was codesigned with Apunipima Cape York Health Council that supports the delivery of primary healthcare for 11 communities in Far North Queensland. We framed our study around the WHO global standards for high-quality health services for adolescents, adding an additional standard around culturally safe care. The study is participatory and mixed methods in design and builds on the recommended WHO assessment tools. Formative qualitative research with young people and their communities (exploring concepts in the WHO recommended quantitative surveys) seeks to understand demand-side enablers and barriers to care, as well as preferences for an enhanced response. Supply-side enablers and barriers will be explored through: a retrospective audit of clinic data (to identify current reasons for access and what can be strengthened); an objective assessment of the adolescent friendliness of clinical spaces; anonymous feedback from adolescent clients around quality of care received and what can be improved; and surveys and qualitative interviews with health providers to understand their perspectives and needs to provide enhanced care. This codesigned project has been approved by Apunipima Cape York Health Council and Far North Queensland Human Research Ethics Committee.

Dissemination And Implications: The findings from this project will inform a codesigned accessible and responsive model of primary healthcare for Aboriginal and Torres Strait Islander adolescents.
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http://dx.doi.org/10.1136/bmjopen-2020-046459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094354PMC
April 2021

Identifying Environmental Determinants Relevant to Health and Wellbeing in Remote Australian Indigenous Communities: A Scoping Review of Grey Literature.

Int J Environ Res Public Health 2021 04 15;18(8). Epub 2021 Apr 15.

School of Health Sciences, University of South Australia, Adelaide, SA 5001, Australia.

The high prevalence of preventable infectious and chronic diseases in Australian Indigenous populations is a major public health concern. Existing research has rarely examined the role of built and socio-political environmental factors relating to remote Indigenous health and wellbeing. This research identified built and socio-political environmental indicators from publicly available grey literature documents locally-relevant to remote Indigenous communities in the Northern Territory (NT), Australia. Existing planning documents with evidence of community input were used to reduce the response burden on Indigenous communities. A scoping review of community-focused planning documents resulted in the identification of 1120 built and 2215 socio-political environmental indicators. Indicators were systematically classified using an Indigenous indicator classification system (IICS). Applying the IICS yielded indicators prominently featuring the "community infrastructure" domain within the built environment, and the "community capacity" domain within the socio-political environment. This research demonstrates the utility of utilizing existing planning documents and a culturally appropriate systematic classification system to consolidate environmental determinants that influence health and disease occurrence. The findings also support understanding of which features of community-level built and socio-political environments amenable to public health and social policy actions might be targeted to help reduce the prevalence of infectious and chronic diseases in Indigenous communities.
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http://dx.doi.org/10.3390/ijerph18084167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071139PMC
April 2021

Hazardous and harmful alcohol use in the Northern Territory, Australia: the impact of alcohol policy on critical care admissions using an extended sampling period.

Addiction 2021 10 23;116(10):2653-2662. Epub 2021 Apr 23.

Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

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.
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http://dx.doi.org/10.1111/add.15432DOI Listing
October 2021

Surgical and percutaneous management of Aboriginal Australians with rheumatic heart disease: Timeliness and concordance between practice and guidelines.

Int J Cardiol 2021 07 18;335:80-84. Epub 2021 Apr 18.

Aboriginal Health Equity Theme, South Australian Health and Medical Research Institute, Adelaide, Australia; Adelaide Medical School, The University of Adelaide, Adelaide, Australia.

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<0.001).

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.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.030DOI Listing
July 2021

Rheumatic heart disease in Indigenous young peoples.

Lancet Child Adolesc Health 2021 06 9;5(6):437-446. Epub 2021 Mar 9.

Telethon Kids Institute, University of Western Australia, Perth Children's Hospital, Perth, WA, Australia.

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.
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http://dx.doi.org/10.1016/S2352-4642(20)30308-4DOI Listing
June 2021

Elevated HDL-bound miR-181c-5p level is associated with diabetic vascular complications in Australian Aboriginal people.

Diabetologia 2021 Jun 2;64(6):1402-1411. Epub 2021 Mar 2.

South Australian Health and Medical Research Institute, Adelaide, SA, Australia.

Aims/hypothesis: 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.

Methods: 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.

Results: 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 < 0.05) and T2DM (82 ± 77%, p < 0.05) groups. Interestingly, we observed a positive correlation between HDL-associated miR-181c-5p levels and disease severity (p = 0.0020). Under high-glucose conditions, cells treated with rHDL, Healthy HDL and T2DM HDL had increased numbers of tubules (rHDL: 136 ± 8%, p < 0.01; Healthy HDL: 128 ± 6%, p < 0.01; T2DM HDL: 124 ± 5%, p < 0.05) and branch points (rHDL: 138 ± 8%, p < 0.001; Healthy HDL: 128 ± 6%, p < 0.01; T2DM HDL: 127 ± 5%, p < 0.01) concomitant with elevations in mRNA levels of the key hypoxia angiogenic transcription factor HIF1A (rHDL: 140 ± 10%, p < 0.01; Healthy HDL: 136 ± 8%, p < 0.01; T2DM HDL: 133 ± 9%, p < 0.05). However, this increase in angiogenic capacity was not observed in cells treated with T2DM + Comp HDL (tubule numbers: 113 ± 6%, p = 0.32; branch points: 113 ± 5%, p = 0.28; HIF1A: 117 ± 6%, p = 0.43), which could be attributed to the increase in cellular miR-181c-5p levels (T2DM + Comp HDL: 136 ± 7% vs PBS: 100 ± 9%, p < 0.05).

Conclusions/interpretation: In conclusion, HDL from Aboriginal people with diabetic complications had reduced angiogenic capacity. This impairment is associated with an increase in the expression of anti-angiogenic miR-181c-5p. These findings provide the rationale for a new way to better inform clinical diagnosis of disease severity with the potential to incorporate targeted, personalised HDL-miRNA intervention therapies to prevent further development of, or to reverse, diabetic vascular complications in Australian Aboriginal people.
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http://dx.doi.org/10.1007/s00125-021-05414-6DOI Listing
June 2021

Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy.

J Clin Invest 2021 03;131(5)

Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

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.I668F 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.
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http://dx.doi.org/10.1172/JCI142148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919725PMC
March 2021

Oral health of aboriginal people with kidney disease living in Central Australia.

BMC Oral Health 2021 02 4;21(1):50. Epub 2021 Feb 4.

Australian Research Centre for Population Oral Health, Adelaide Dental School, The University of Adelaide, Adelaide, Australia.

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.
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http://dx.doi.org/10.1186/s12903-021-01415-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863237PMC
February 2021

Alcohol misuse and critical care admissions in the Northern Territory.

Intern Med J 2021 Sep;51(9):1433-1440

Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

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 < 0.01) and had longer ICU (2.8 vs 2.1 days, P < 0.01) and hospital LoS (9.1 vs 7.1 days, P < 0.01). There was no difference in hospital mortality (7.2% vs 7.7%, P = 0.94), even after adjustment for illness severity, hospital and diagnostic category.

Conclusions: Alcohol misuse is associated with a substantial number of critical care admissions and consumes considerable acute care resources. Further policy directed at harm minimisation and epidemiological work at jurisdictional and national level is necessary.
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http://dx.doi.org/10.1111/imj.15212DOI Listing
September 2021
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