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Abstract Background Aboriginal and Torres Strait Islander peoples are disproportionately impacted by type 2 diabetes. Continuous glucose monitoring (CGM) technology (such as Abbott Freestyle Libre 2, previously referred to as Flash Glucose Monitoring) offers real-time glucose monitoring that is convenient and easy to use compared to self-monitoring of blood glucose (SMBG). However, this technology’s use is neither widespread nor subsidised for Aboriginal and Torres Strait Islander peoples with type 2 diabetes. Building on existing collaborations with a national network of Aboriginal and Torres Strait Islander communities, this randomised controlled trial aims to assess the effect of CGM compared to SMBG on (i) haemoglobin A1c (HbA1c), (ii) achieving blood glucose targets, (iii) reducing hypoglycaemic episodes and (iv) cost-effective healthcare in an Aboriginal and Torres Strait Islander people health setting. Methods This is a non-masked, parallel-group, two-arm, individually randomised, controlled trial (ACTRN12621000753853). Aboriginal and Torres Strait Islander adults with type 2 diabetes on injectable therapy and HbA1c ≥ 7.5% (n = 350) will be randomised (1:1) to CGM or SMBG for 6 months. The primary outcome is change in HbA1c level from baseline to 6 months. Secondary outcomes include (i) CGM-derived metrics, (ii) frequency of hypoglycaemic episodes, (iii) health-related quality of life and (iv) incremental cost per quality-adjusted life year gained associated with the CGM compared to SMBG. Clinical trial sites include Aboriginal Community Controlled Organisations, Aboriginal Medical Services, primary care centres and tertiary hospitals across urban, rural, regional and remote Australia. Discussion The trial will assess the effect of CGM compared to SMBG on HbA1c for Aboriginal and Torres Strait Islander people with type 2 diabetes in Australia. This trial could have long-term benefits in improving diabetes management and providing evidence for funding of CGM in this population. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12621000753853. Registered on 15th June 2021.

Abstract Background Type 2 diabetes mellitus (T2DM) is highly prevalent within the Indigenous Australian community. Novel glucose monitoring technology offers an accurate approach to glycaemic management, providing real-time information on glucose levels and trends. The acceptability and feasibilility of this technology in Indigenous Australians with T2DM has not been investigated. Objective This feasibility phenomenological study aims to understand the experiences of Indigenous Australians with T2DM using flash glucose monitoring (FGM). Methods Indigenous Australians with T2DM receiving injectable therapy (n = 8) who used FGM (Abbott Freestyle Libre) for 6-months, as part of a clinical trial, participated in semi-structured interviews. Thematic analysis of the interviews was performed using NVivo12 Plus qualitative data analysis software (QSR International). Results Six major themes emerged: 1) FGM was highly acceptable to the individual; 2) FGM’s convenience was its biggest benefit; 3) data from FGM was a tool to modify lifestyle choices; 4) FGM needed to be complemented with health professional support; 5) FGM can be a tool to engage communities in diabetes management; and 6) cost of the device is a barrier to future use. Conclusions Indigenous Australians with T2DM had positive experiences with FGM. This study highlights future steps to ensure likelihood of FGM is acceptable and effective within the wider Indigenous Australian community.

Abstract Background Cancer 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 Fraction of Life Years Lost After Diagnosis (FLYLAD) is one such burden measure. We use data on Aboriginal and non-Aboriginal South Australians from 1990 to 2010 to show how FLYLAD 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. Method FLYLADcancer is the fraction 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. FLYLADcancer 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. Results Cancers diagnoses (N = 144,891) included 777 among Aboriginal people. Cancer burden described by FLYLADcancer 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 FLYLADcancer 0.44, 95% CIs 0.40–0.47 and 0.28, 95% CIs 0.25–0.31 respectively. Conclusion FLYLAD 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. FLYLAD’s use of readily available, person-level administrative records can help evaluate health care initiatives addressing this need.

Abstract Background Aboriginal and Torres Strait Islander peoples (hereafter respectfully referred to as Indigenous Australians) represent about 3% of the total Australian population. Major health disparities exist between Indigenous and Non-Indigenous Australians. To address this, it is vital to understand key health priorities and knowledge gaps in the current landscape of clinical trial activity focusing on Indigenous health in Australia. Methods Australian-based clinical trials registered on the Australian New Zealand Clinical Trials Registry or ClinicalTrials.gov from 2008 to 2018 were analysed. Australian clinical trials with and without a focus on Indigenous health were compared in terms of total numbers, participant size, conditions studied, design, intervention type and funding source. Results Of the 9206 clinical trials included, 139 (1.5%) focused on Indigenous health, with no proportional increase in Indigenous trials over the decade (p = 0.30). Top conditions studied in Indigenous-focused trials were mental health (n = 35, 28%), cardiovascular disease (n = 20, 20%) and infection (n = 16, 16%). Compared to General Australian trials, Indigenous-focused trials more frequently studied ear conditions (OR 20.26, 95% CI 10.32–37.02, p

Abstract 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.

Abstract 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.

Abstract 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.

Abstract 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.

Abstract Background Australia’s Aboriginal and Torres Strait Islander women have poorer survival and twice the disease burden from breast cancer compared to other Australian women. These disparities are influenced, but not fully explained, by more diagnoses at later stages. Incorporating breast screening, hospital and out of hospital treatment and cancer registry records into a person-linked data system can improve our understanding of breast cancer outcomes. We focussed one such system on a population-based cohort of Aboriginal women in South Australia diagnosed with breast cancer and a matched cohort of non-Aboriginal women with breast cancer. We quantify Aboriginal and non-Aboriginal women’s contact with publicly funded screening mammograms; quantify exposure to a selection of cancer treatment modalities; then assess the relationship between screening, treatment and the subsequent risk of breast cancer death. Methods Breast cancers registered among Aboriginal women in South Australia in 1990–2010 (N = 77) were matched with a random selection of non-Aboriginal women by birth and diagnostic year, then linked to screening records, and treatment 2 months before and 13 months after diagnosis. Competing risk regression summarised associations of Aboriginality, breast screening, cancer stage and treatment with risk of breast cancer death. Results Aboriginal women were less likely to have breast screening (OR = 0.37, 95%CIs 0.19–0.73); systemic therapies (OR = 0.49, 95%CIs 0.24–0.97); and, surgical intervention (OR = 0.35, 95%CIs 0.15–0.83). Where surgery occurred, mastectomy was more common among Aboriginal women (OR = 2.58, 1.22–5.46). Each of these factors influenced the risk of cancer death, reported as sub-hazard ratios (SHR). Regional spread disease (SHR = 34.23 95%CIs 6.76–13.40) and distant spread (SHR = 49.67 95%CIs 6.79–363.51) carried more risk than localised disease (Reference SHR = 1). Breast screening reduced the risk (SHR = 0.07 95%CIs 0.01–0.83). So too did receipt of systemic therapy (SHR = 0.06 95%CIs 0.01–0.41) and surgical treatments (SHR = 0.17 95%CIs 0.04–0.74). In the presence of adjustment for these factors, Aboriginality did not further explain the risk of breast cancer death. Conclusion Under-exposure to screening and treatment of Aboriginal women with breast cancers in South Australia contributed to excess cancer deaths. Improved access, utilisation and quality of effective treatments is needed to improve survival after breast cancer diagnosis.

Abstract Background Aboriginal and Torres Strait Islander men have the highest morbidity and mortality rates, and lowest rates of health service utilization in Australia. There is a current perception that Aboriginal and Torres Strait Islander men are disinterested in their health. This study aimed to identify the perceived motivators, barriers and enablers of Aboriginal and Torres Strait Islander men’s utilization of primary health care services, explore their experiences and obtain suggestions from them as to how services could be modified to improve utilization. Methods This study utilized the principles of Indigenist Research Methods. Semi-structured interviews with Aboriginal and Torres Strait Islander men (N = 19) took place in South Australia and far north Queensland. Participants were asked about their experiences with primary health care services, including what they could remember as a child. A thematic analysis of the qualitative data was completed without the use of computer software. Results Feelings of invincibility, shame, being uncomfortable, fearful, along with long waiting times, having a lack of knowledge, and culturally inappropriate staff/services were all found to be barriers to service utilization. Enabling factors included convenience, the perceived quality of the service, feeling culturally safe and/or a sense of belonging, and having a rapport with staff. Motivation for attending primary health care services included going when feeling sick/unwell, attending a particular service (dental or sexual health), visiting for check-ups and preventative health and family encouragement. This study also highlights strategies surrounding logistical factors, promotion of services and improved communications, having culturally appropriate services and providing gender specific services all of which were suggested by the participants to improve service utilization. Conclusion Contrary to common misperceptions, this study demonstrated that most of the Aboriginal and Torres Strait Islander men participants were motivated to engage with primary health care services for preventative health care. Even though there were men that fitted the stereo-type who avoid doctors, there were usually underlying reasons and barriers accounting for this reluctance. This study suggests that if primary health care services commit to better understanding the barriers, enablers and motivators their cohort of men face, then utilization could be greatly improved.

Abstract Background Aboriginal and Torres Strait Islander men experience worse health outcomes and are the most marginalized and disadvantaged population group in Australia. Primary health care services are critical to providing both clinical and social and emotional support, however, remain underutilized by Aboriginal and Torres Strait Islander men. This review aims to better understand the utilization of primary health care services by Indigenous men and assess the effectiveness of strategies implemented to improve utilization. Methods A four-step search strategy was employed across four databases to find peer-reviewed publications and grey literature from Australia, New Zealand, Canada and America. The search began in March 2015 and included the following databases PubMed, CINAHL, Informit (Indigenous collection) and Embase. Additional databases and websites were also searched for grey literature, reference lists of included publications were searched for additional studies and relevant experts were consulted. Results The literature search found seven articles that met the inclusion criteria; four describing three research projects, plus three expert opinion pieces. The search was unable to find published research on strategies implemented to improve primary health care utilization by Indigenous men. There is limited published research focused on the utilization of primary health care by Indigenous men. From the identified papers Indigenous men described factors impacting utilization which were categorized into three primary organizing themes; those related to health services, the attitudes of Indigenous men and knowledge. It is evident from the identified papers that improvements in Indigenous health can only occur if future programs are developed in collaboration with health services and Indigenous men to address differing requirements. Conclusions Currently, health systems in Australia are limited in their ability to improve the health and wellbeing of Aboriginal and Torres Strait Islander males without such strategies. Future research should focus on evaluating the implementation of men specific utilization strategies. It is through evidence-based research that subsequent policies and programs can be made and implemented to improve Indigenous men’s health.

Abstract Background Indigenous populations have poorer health outcomes compared to their non-Indigenous counterparts. The evolution of Indigenous primary health care services arose from mainstream health services being unable to adequately meet the needs of Indigenous communities and Indigenous peoples often being excluded and marginalised from mainstream health services. Part of the solution has been to establish Indigenous specific primary health care services, for and managed by Indigenous peoples. There are a number of reasons why Indigenous primary health care services are more likely than mainstream services to improve the health of Indigenous communities. Their success is partly due to the fact that they often provide comprehensive programs that incorporate treatment and management, prevention and health promotion, as well as addressing the social determinants of health. However, there are gaps in the evidence base including the characteristics that contribute to the success of Indigenous primary health care services in providing comprehensive primary health care. This systematic scoping review aims to identify the characteristics of Indigenous primary health care service delivery models. Method This systematic scoping review was led by an Aboriginal researcher, using the Joanna Briggs Institute Scoping Review Methodology. All published peer-reviewed and grey literature indexed in PubMed, EBSCO CINAHL, Embase, Informit, Mednar, and Trove databases from September 1978 to May 2015 were reviewed for inclusion. Studies were included if they describe the characteristics of service delivery models implemented within an Indigenous primary health care service. Sixty-two studies met the inclusion criteria. Data were extracted and then thematically analysed to identify the characteristics of Indigenous PHC service delivery models. Results Culture was the most prominent characteristic underpinning all of the other seven characteristics which were identified – accessible health services, community participation, continuous quality improvement, culturally appropriate and skilled workforce, flexible approach to care, holistic health care, and self-determination and empowerment. Conclusion While the eight characteristics were clearly distinguishable within the review, the interdependence between each characteristic was also evident. These findings were used to develop a new Indigenous PHC Service Delivery Model, which clearly demonstrates some of the unique characteristics of Indigenous specific models.

Abstract Background Re-defining the way in which care is delivered, to reflect Aboriginal and Torres Strait Islander peoples’ needs and values, is essential for improving the accessibility of primary healthcare. This study focused on developing a Framework to support the quality of care and quality of life of, as well as treatment for, Aboriginal and Torres Strait Islander peoples living with chronic disease. Methods A team of researchers, including thirteen experienced Aboriginal healthcare professionals, came together to undertake this important work. Using a Participatory Action Approach, this study actively engaged people with local knowledge to ensure that the Framework was developed by and for Aboriginal people. Results The final Wellbeing Framework consists of two core values and four elements, each supported by four principles. Importantly, the Framework also includes practical examples of how the principles could be applied. National Reference Group members, including community representatives, policy makers and healthcare providers, reviewed and approved the final Framework. Conclusion The outcome of this collaborative effort is a Framework to guide primary healthcare services to develop locally relevant, flexible approaches to care which can respond to communities’ and individuals’ varied understandings of wellbeing.

Abstract Background In spite of bearing a heavier burden of death, disease and disability, there is mixed evidence as to whether Indigenous Australians utilise more or less healthcare services than other Australians given their elevated risk level. This study analyses the Medicare expenditure and its predictors in a cohort of Indigenous and non-Indigenous Australians at high risk of cardiovascular disease. Methods The healthcare expenditure of participants of the Kanyini Guidelines Adherence with the Polypill (GAP) pragmatic randomised controlled trial was modelled using linear regression methods. 535 adult (48% Indigenous) participants at high risk of cardiovascular disease (CVD) were recruited through 33 primary healthcare services (including 12 Aboriginal Medical Services) across Australia. Results There was no significant difference in the expenditure of Indigenous and non-Indigenous participants in non-remote areas following adjustment for individual characteristics. Indigenous individuals living in remote areas had lower MBS expenditure ($932 per year P

Abstract 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.