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Refereed/Peer-reviewed Aim: To examine whether differences in tacrolimus and mycophenolic acid (MPA) pharmacokinetics contribute to the poorer kidney transplant outcomes experienced by Aboriginal Australians. Methods: Concentration-time profiles for tacrolimus and MPA were prospectively collected from 43 kidney transplant recipients: 27 Aboriginal and 16 Caucasian. Apparent clearance (CL/F) and distribution volume (V/F) for each individual were derived from concentration-time profiles combined with population pharmacokinetic priors, with subsequent assessment for between-group difference in pharmacokinetics. In addition, population pharmacokinetic models were developed using the prospective dataset supplemented by previously developed structural models for tacrolimus and MPA. The change in NONMEM objective function was used to assess improvement in goodness of model fit. Results: No differences were found between Aboriginal and Caucasian groups or empirical Bayes estimates, for CL/F or V/F of MPA or tacrolimus. However, a higher prevalence of CYP3A5 expressers (26% compared with 0%) and wider between-subject variability in tacrolimus CL/F (SD = 5.00 compared with 3.25 L/h/70 kg) were observed in the Aboriginal group, though these differences failed to reach statistical significance (p = .07 and p = .08). Conclusion: There were no differences in typical tacrolimus or MPA pharmacokinetics between Aboriginal and Caucasian kidney transplant recipients. This means that Bayesian dosing tools developed to optimise tacrolimus and MPA dosing in Caucasian recipients may be applied to Aboriginal recipients. In turn, this may improve drug exposure and thereby transplant outcomes in this group. Aboriginal recipients appeared to have greater between-subject variability in tacrolimus CL/F and a higher prevalence of CYP3A5 expressers, attributes that have been linked with inferior outcomes.

Background Community-based weight loss programs may have potential to address overweight and obesity at the population level. However, participation patterns and individual outcomes from these programs are understudied. This study examined repeat participation patterns and participant weight change between contests over seven years of an Aboriginal Australian team-based program in order to identify (1) predictors of repeat participation and (2) associations with weight change between contests. Methods Data for the 12 contests from 2012 to 2018 were merged, with probabilistic record matching. A total of 7510 enrolments were registered for the 12 contests, representing 4438 unique people. Contest lengths varied from 10 to 16 weeks in duration. Non-repeat participants were those who only competed once in the program by the end of 2018, and repeaters were those who competed in at least two contests. Associations between repeat participation and participant baseline (i.e., first participation occasion) characteristics, change in diet and physical activity and percent change in weight during the first participation occasion were examined using crossed random effects (for person and team) regression adjusted for exposure to the program. Weight percentage change between contests was calculated for consecutive participation occasions occurring at least three months apart, converted to percent change per month. Weight change was regressed on number of repeat participation occasions adjusted for age, gender, baseline weight at first participation occasion, and weight percent change in the immediately preceding contest. Results One-third of the 4433 participants participated more than once, with women more likely than men to repeat. A 1% reduction in weight during a competition was associated with an increase in weight of 0.05% per month between competition end and subsequent participation. Regain was smaller the heavier participants were at their first participation. Conclusions While individuals benefit from weight loss through program participation, strengthening strategies for weight loss maintenance within or following the program could improve long-term weight outcomes and reduce weight cycling.

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.

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.

The hormone thyroxine that regulates mammalian metabolism is carried and stored in the blood by thyroxine-binding globulin (TBG). We demonstrate here that the release of thyroxine from TBG occurs by a temperature-sensitive mechanism and show how this will provide a homoeostatic adjustment of the concentration of thyroxine to match metabolic needs, as with the hypothermia and torpor of small animals. In humans, a rise in temperature, as in infections, will trigger an accelerated release of thyroxine, resulting in a predictable 23% increase in the concentration of free thyroxine at 39°C. The in vivo relevance of this fever-response is affirmed in an environmental adaptation in aboriginal Australians. We show how two mutations incorporated in their TBG interact in a way that will halve the surge in thyroxine release, and hence the boost in metabolic rate that would otherwise occur as body temperatures exceed 37°C. The overall findings open insights into physiological changes that accompany variations in body temperature, as notably in fevers.

IntroductionAdopting a process-oriented framework for test validation can help to establish whether this tool has the potential to be an acceptable, valid and reliable indicator of depression for mothers and mothers-to-be. This mixed-methods research protocol seeks to explore the views and experiences of Aboriginal mothers and healthcare professionals in relation to the Edinburgh Postnatal Depression Scale (EPDS), and is intended to highlight potential barriers in perinatal mental health conceptualisation, engagement and response style.Methods and analysisThematic analysis will be applied to interview transcripts of Aboriginal Australian mothers (n=6+) and healthcare professionals (n=6+) to identify key themes. The process-focused validation model will use narratives about experiences of using the EPDS as the priority point of analysis. Item-level data and process-level (experience) data are key phenomenological data. The interview-based narratives will be then compared with EPDS scores to check for points of congruence and divergence. This will be done at two time points, antenatally and postnatally, to assess changes in assessment processes and perceptions. Bridging evidence-based research with clinical practice in an Aboriginal Australian context will be facilitated by an investigation of the perceived cultural relevance and likely clinical effectiveness of EPDS. Such evidence is critical to understanding whether the EPDS fulfils its intended purpose. The guiding principles in designing this research protocol is to benefit the well-being of young Aboriginal families and communities through partnership with Aboriginal women.Ethics and disseminationEthics approval was obtained from Human Research Ethics Committee of Murdoch University and from Western Australian Aboriginal Health Ethics Committee (WAAHEC). Participating healthcare sites and services have provided letters of support. Results of this study will be submitted for publication in a peer-reviewed journal.

All available data suggest that, like many other Indigenous peoples, Australian Aborigines are significantly more like to kill themselves than are non-Aboriginal Australians. This statistical disparity is normally positioned an objective, ontological and undeniable social fact, a fact best explained as a function of endemic community disadvantage and disenfranchisement. This research explores the possibility that higher-than-normal Aboriginal suicide rates may also be a function of coronial decision-making practices. Based upon in-depth interviews with 32 coroners from across Australia, the following conclusions emerged from the data. First, coroners have differing perceptions of Indigenous capacity, and are less likely to have concerns about intent when the suicide is committed by an Indigenous person. Second, coroners have identified divergent scripts of Indigenous suicide, particularly its spontaneity and public location, and this supports rather than challenges, a finding of suicide. Third, the coronial perception of Indigenous life is a factor which influences a suicide determination for Indigenous deaths. Finally, the low level of Indigenous engagement with the coronial system, and the unlikelihood of a challenge to the finding of suicide by Indigenous families, means that a coronial determination of suicide is more likely.

This subspecies is common in communities with high rates of streptococcal disease, and its epidemiology differs from that of Streptococcus pyogenes., Streptococcus dysgalactiae subsp. equisimilis (groups C and G streptococci [GCS/GGS]) is an increasingly recognized human pathogen, although it may follow indirect pathways. Prospective surveillance of selected households in 3 remote Aboriginal communities in Australia provided 337 GCS/GGS isolates that were emm sequence-typed. Lancefield group C isolates (GCS) were localized to specific households and group G isolates (GGS) were more evenly distributed. GCS/GGS was more frequently recovered from the throat than group A streptococci (GAS [S. pyogenes]) but rarely recovered from skin sores, and then only with Staphylococcus aureus or GAS. Symptomatic GGS/GGC pharyngitis was also rare. Specific emm sequence types of GCS/GGS did not appear to cycle through the communities (sequential strain replacement) in a manner suggesting acquisition of type-specific immunity. These communities already have high levels of streptococcal and poststreptococcal disease. GCS/GGS may increase in importance as it acquires key virulence factors from GAS by lateral gene transfer.

Chronic heart failure (CHF) among Aboriginal/Indigenous Australians is endemic. There are also grave concerns for outcomes once acquired. This point is compounded by a lack of prospective and objective studies to plan care. To capture the essence of the presented topic it is essential to broadly understand Indigenous health. Key words such as 'worsening', 'gaps', 'need to do more', 'poorly studied', or 'future studies should inform' occur frequently in contrast to CHF research for almost all other groups. This narrative styled opinion piece attempts to discuss future directions for CHF care for Indigenous Australians. We provide a synopsis of the problem, highlight the treatment gaps, and define the impediments that present hurdles in optimising CHF care for Indigenous Australians.

The hormone thyroxine that regulates mammalian metabolism is carried and stored in the blood by thyroxine-binding globulin (TBG). We demonstrate here that the release of thyroxine from TBG occurs by a temperature-sensitive mechanism and show how this will provide a homoeostatic adjustment of the concentration of thyroxine to match metabolic needs, as with the hypothermia and torpor of small animals. In humans, a rise in temperature, as in infections, will trigger an accelerated release of thyroxine, resulting in a predictable 23% increase in the concentration of free thyroxine at 39°C. The in vivo relevance of this fever-response is affirmed in an environmental adaptation in aboriginal Australians. We show how two mutations incorporated in their TBG interact in a way that will halve the surge in thyroxine release, and hence the boost in metabolic rate that would otherwise occur as body temperatures exceed 37°C. The overall findings open insights into physiological changes that accompany variations in body temperature, as notably in fevers.

We examined genetic affinities of Aboriginal Australian and New Guinean populations by using nucleotide variation in the two hypervariable segments of the mtDNA control region (CR). A total of 318 individuals from highland Papua New Guinea (PNG), coastal PNG, and Aboriginal Australian populations were typed with a panel of 29 sequence-specific oligonucleotide (SSO) probes. The SSO-probe panel included five new probes that were used to type an additional 1,037 individuals from several Asian populations. The SSO-type data guided the selection of 78 individuals from Australia and east Indonesia for CR sequencing. A gene tree of these CR sequences, combined with published sequences from worldwide populations, contains two previously identified highland PNG clusters that do not include any Aboriginal Australians; the highland PNG clusters have coalescent time estimates of approximately 80,000 and 122,000 years ago, suggesting ancient isolation and genetic drift. SSO-type data indicate that 84% of the sample of PNG highlander mtDNA belong to these two clusters. In contrast, the Aboriginal Australian sequences are intermingled throughout the tree and cluster with sequences from multiple populations. Phylogenetic and multidimensional-scaling analyses of CR sequences and SSO types split PNG highland and Aboriginal Australian populations and link Aboriginal Australian populations with populations from the subcontinent of India. These mtDNA results do not support a close relationship between Aboriginal Australian and PNG populations but instead suggest multiple migrations in the peopling of Sahul.

Background: The prevalence of Helicobacter pylori infection among Aboriginal Australians children is unclear. The aims of the present study are to determine the prevalence of H. pylori infection among young Aboriginal children recovering from acute diarrheal disease in hospital and to evaluate the H. pylori stool antigen test as a noninvasive diagnostic test in this setting. Methods: This was a prospective comparative study using the 13C-Urea Breath Test as reference standard. Fifty-two children between 4 months and 2 years of age were consecutively enrolled. These children comprised a representative sample of Australian Aboriginal children admitted to hospital with acute diarrheal disease from remote and rural communities across Northern Territory of Australia. Results: The overall prevalence of H. pylori was 44.2%. The stool antigen test had a sensitivity of 0.55 (95% confidence interval CI: 0.35– 0.73) with a positive predictive value of 0.65 (95% CI: 0.42–0.82). The specificity was 0.68 (95% CI: 0.46–0.84) with a negative predictive value of 0.58 (95% CI: 0.39–0.75). Analysis of receiver operator characteristic curve yielded an overall accuracy of the stool antigen test of 61% (48%–75%). Conclusions: The prevalence of H. pylori infection among very young Aboriginal children from remote and rural communities was high and consistent with early acquisition. The diagnostic accuracy of the stool antigen test to diagnose H. pylori in this setting was poor.