Reflections as a settler person doing research in collaboration with Indigenous peoples.

Objectives To reflect on my position as a settler person in Australia and ensure Indigenous voices are prioritised throughout my research, as part of a co-designed, Aboriginal-led study which aims to understand trends in the removal of Indigenous children born in Western Australia using data linkage and qualitative research. Approach As a non-Indigenous person, it is important to reflect on my cultural background and acknowledge my limited understanding of the cultural context of the Indigenous communities represented in the data. Listening to Indigenous voices and collaborating with Indigenous peoples at all stages of my research – from my PhD supervisor to investigators on the broader study, to members of the community and policy reference groups – will be key to improve my understanding of the data from a system and context I am unfamiliar with. Results Collaboration has been cyclical, with results from the qualitative research and discussion with the reference groups informing the initial quantitative research direction. Findings from this research were presented back to the groups, resulting in further questions and directions to explore. The journey so far has been one of learning and understanding the skills I have and the role they can play whilst acknowledging the limits of my own knowledge and the need for Indigenous voices to guide the research in order to be doing research with Indigenous peoples, rather than on them. Conclusion Co-design with Indigenous peoples is critical for doing research which affects them or uses data from their communities. Understanding my own cultural background and acknowledging the limitations of my experience continues to be important for honest and meaningful collaboration

Cumulative incidence of child protection system contacts among a cohort of Western Australian Aboriginal children born 2000 to 2013

Background: Reducing the over-representation of Aboriginal children in the child protection system is a key target for the Australian government. Objective: We aimed to provide more recent evidence on the population-level cumulative incidence of contacts for Aboriginal children with child protective services (CPS) in Western Australia (WA). Participants and Setting: Linked administrative data was provided for WA CPS between 2000 and 2015 for 33,709 Aboriginal children born in WA between 2000 and 2013. Methods: Descriptive summaries and cumulative incidence estimates were used to examine changes in CPS contact trends over time and within sibling groups. Results: There was an increase in early-childhood contacts for children born more recently, with 7.6 % and 2.3 % of children born in 2000–2001 having a notification and placement in out-of-home care by age one, respectively, compared to 15.1 % and 4.3 % of children born in 2012–2013. Among sibling groups where at least one sibling had a CPS contact, approximately half of children had their first contacts on the same date as another sibling. For children born after one of their siblings had been placed in out-of-home care, 31.9 % had themselves been placed in out-of-home care by age one. Conclusions: Multiple children tend to be placed into out-of-home care when at least one sibling is, which is likely to have a significant impact on families affected. The additional risk of placement also carries over to children born after the first removal in a sibling group, highlighting the need for further support to prevent future removals

A randomised controlled trial of email versus mailed invitation letter in a national longitudinal survey of physicians.

Despite their low cost, the use of email invitations to distribute surveys to medical practitioners have been associated with lower response rates. This research compares the difference in response rates from using email approach plus online completion rather than a mailed invitation letter plus a choice of online or paper completion. A parallel randomised controlled trial was conducted during the 11th annual wave of the nationally representative Medicine in Australia: Balancing Employment and Life (MABEL) longitudinal survey of doctors. The control group was invited using a mailed paper letter (including a paper survey plus instructions to complete online) and three mailed paper reminders. The intervention group was approached in the same way apart from the second reminder when they were approached by email only. The primary outcome is the response rate and the statistical analysis was blinded. 18,247 doctors were randomly allocated to the control (9,125) or intervention group (9,127), with 9,108 and 9,107 included in the analysis. Using intention to treat analysis, the response rate in the intervention group was 35.92% compared to 37.59% in the control group, a difference of -1.66 percentage points (95% CI: -3.06 to -0.26). The difference was larger for General Practitioners (-2.76 percentage points, 95% CI: -4.65 to -0.87) compared to other specialists (-0.47 percentage points, 95% CI: -2.53 to 1.60). For those who supplied an email address, the average treatment effect on the treated was higher at -2.63 percentage points (95% CI: -4.50 to -0.75) for all physicians, -3.17 percentage points (95% CI: -5.83 to -0.53) for General Practitioners, and -2.1 percentage points (95% CI: -4.75 to 0.56) for other specialists. For qualified physicians, using email to invite participants to complete a survey leads to lower response rates compared to a mailed letter. Lower response rates need to be traded off with the lower costs of using email rather than mailed letters

Genome-wide association studies of hypertension: have they been fruitful?

Over the last two decades candidate gene association studies and genome-wide linkage scans have met with little success in characterizing risk variants for hypertension. Several factors could be responsible for the relative lack of success, although our understanding of the genetics has evolved to support the belief that there are multiple common risk variants, which are associated with hypertension with modest effect sizes. Genome-wide association studies (GWAS) have successfully identified risk loci for several complex polygenic disease states. Until recently, the productivity of GWAS with respect to identifying risk loci for hypertension was limited. In this paper we describe the recent success of GWAS of hypertension in identifying over a dozen loci associated with essential hypertension. We will review these findings, and place these results in the context of the future potential of pharmocogenetics of hypertension

Kidney omics in hypertension: from statistical associations to biological mechanisms and clinical applications

Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage

Risks of cardiovascular events and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the ADVANCE study.

Contains fulltext : 81639.pdf (publisher's version ) (Closed access)AIMS: The aim of this study was to investigate serious clinical outcomes associated with atrial fibrillation (AF) and the effects of routine blood pressure lowering on such outcomes in the presence or absence of AF, among individuals with type 2 diabetes. METHODS AND RESULTS: About 11 140 patients with type 2 diabetes (7.6% of whom had AF at baseline) were randomized to a fixed combination of perindopril and indapamide or placebo in the Action in Diabetes and Vascular Disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. We compared total mortality and cardiovascular disease outcomes and effects of randomized treatment for 4.3 years on such outcomes between patients with and without AF at baseline. After multiple adjustments, AF was associated with a 61% (95% confidence interval 31-96, P < 0.0001) greater risk of all-cause mortality and comparable higher risks of cardiovascular death, stroke, and heart failure (all P < 0.001). Routine treatment with a fixed combination of perindopril and indapamide produced similar relative, but greater absolute, risk reductions for all-cause and cardiovascular mortalities in patients with AF, compared with those without AF. The number of patients needed to be treated with perindopril-indapamide for 5 years to prevent one cardiovascular death was 42 for patients with AF and 120 for patients without AF at baseline. CONCLUSION: Atrial fibrillation is relatively common in type 2 diabetes and is associated with substantially increased risks of death and cardiovascular events in patients with type 2 diabetes. This arrhythmia identifies individuals who are likely to obtain greater absolute benefits from blood pressure-lowering treatment. Atrial fibrillation in diabetic patients should be regarded as a marker of particularly adverse outcome and prompt aggressive management of all risk factors