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Objective: Mitochondria have an important role in the induction of the NLRP3 inflammasome response central in gout. The objective was to test whether mitochondrial genetic variation and copy number in New Zealand Māori and Pacific (Polynesian) people in Aotearoa New Zealand associate with susceptibility to gout.Methods: 437 whole mitochondrial genomes from Māori and Pacific people (predominantly men) from Aotearoa New Zealand (327 people with gout, 110 without gout) were sequenced. Mitochondrial DNA copy number variation was determined by assessing relative read depth using data produced from whole genome sequencing (32 cases, 43 controls) and targeted resequencing of urate loci (151 cases, 222 controls). Quantitative PCR was undertaken for replication of copy number findings in an extended sample set of 1159 Māori and Pacific men and women (612 cases, 547 controls).Results: There was relatively little mitochondrial genetic diversity, with around 96% of those sequenced in this study belonging to the B4a1a and derived sublineages. A B haplogroup heteroplasmy in hypervariable region I was found to associate with a higher risk of gout among the mitochondrial sequenced sample set (position 16181: OR=1.57, P=0.001). Increased copies of mitochondrial DNA were found to protect against gout risk with the effect being consistent when using hyperuricaemic controls across each of the three independent sample sets (OR=0.89, P=0.007; OR=0.90, P=0.002; OR=0.76, P=0.03). Paradoxically, an increase of mitochondrial DNA also associated with an increase in gout flare frequency in people with gout in the two larger sample sets used for the copy number analysis (β=0.003, P=7.1×10-7; β=0.08, P=1.2×10-4).Conclusion: Association of reduced copy number with gout in hyperuricaemia was replicated over three Polynesian sample sets. Our data are consistent with emerging research showing that mitochondria are important for the colocalisation of the NLRP3 and ASC inflammasome subunits, a process essential for the generation of interleukin-1β in gout. [ABSTRACT FROM AUTHOR]

Objectives To assess the effect of a customised, structured cardiovascular disease (CVD) medication health literacy programme on medication knowledge among Indigenous people with, or at high risk of, CVD. Design Intervention trial with premeasures and postmeasures at multiple time points. Setting Indigenous primary care services in Australia, Canada and New Zealand. Participants 171 Indigenous people aged ≥20 years of age who had at least one clinical diagnosis of a CVD event, or in Canada and Australia had a 5-year CVD risk ≥15%, and were prescribed at least two of the following CVD medication classes: statin, aspirin, ACE inhibitors and beta blockers. Intervention An education session delivered on three occasions over 1 month by registered nurses or health educators who had received training in health literacy and principles of adult education. An interactive tablet application was used during each session and an information booklet and pill card provided to participants. Primary outcome measures Knowledge about the CVD medications assessed before and after each session. Results Knowledge at baseline (presession 1) was low, with the mean per cent correct answers highest for statins (34.0% correct answers), 29.4% for aspirin, 26.0% for beta blockers and 22.7% for ACE inhibitors. Adjusted analyses showed highly significant (P<0.001) increases in knowledge scores between preassessments and postassessments at all three time points for all medication classes. For the four medications, the absolute increases in adjusted per cent correct items from presession 1 to postsession 3 assessments were 60.1% for statins, 76.8% for aspirin, 71.4% for ACE inhibitor and 69.5% for beta blocker. Conclusions The intervention was highly effective in contextually diverse Indigenous primary healthcare services in Australia, Canada and New Zealand. The findings from this study have important implications for health services working with populations with low health literacy more generally. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVD) are leading causes of mortality and morbidity among Indigenous people in New Zealand, Australia and Canada and are a major driver of the inequities in life expectancy between Indigenous and non-Indigenous people in these countries. Evidence-based pharmaceutical management of CVD can significantly reduce mortality and morbidity for persons diagnosed with CVD or for those at intermediate or high risk of CVD. Health literacy has been identified as a major barrier in the communication and implementation of appropriate pharmaceutical management plans for CVD. Addressing health literacy is particularly relevant in Indigenous populations where there are unique health and adult literacy challenges.Methods/design: This study will examine the effect of a customized, structured CVD medication programme, delivered by health professionals, on the health literacy of Indigenous people with, or at risk, of CVD. Primary outcomes are patient's knowledge about CVD medications; secondary outcomes examine changes in health literacy skills and practices. The study will employ a multi-site pre-post design with multiple measurement points to assess intervention efficacy. Participants will be recruited from four Indigenous primary care services in Australia, Canada and New Zealand. Three educational sessions will be delivered over four weeks. A tablet application will support the education sessions and produce a customized pill card for each participant. Participants will be provided with written information about CVD medications. Medication knowledge scores, and specific health literacy skills and practices will be assessed before and after the three sessions. Statistical analyses will identify significant changes in outcomes over each session, and from the pre-session one to post-session three time points.Discussion: This study will make an important contribution to understanding the effect of a structured primary care-based intervention on CVD health literacy in Indigenous populations. The study also illustrates the incorporation of Indigenous health research principles and processes in clinical trials and provides insights that may be useful in other contexts.Trial Registration: Australian and New Zealand Clinical Trials Register (ACTRN12612001309875; date of registration 18/12/2012). [ABSTRACT FROM AUTHOR]

Introduction: There is emerging evidence for stratified glucose-lowering responses to certain oral medications for type 2 diabetes (T2D) by individual characteristics. The objective of this study was to test whether glycaemic response to representative treatments of dipeptidyl peptidase-4 inhibitors (vildagliptin) and thiazolidinediones (pioglitazone) varies according to ethnicity, gender, baseline obesity, triglyceride level or genetic variation., Methods: This is a multicentre, two-period, two-treatment, open-label, randomised cross-over trial of vildagliptin and pioglitazone as second-line or third-line therapy in patients with T2D who have suboptimal glycaemic control on metformin and/or sulfonylurea therapy. It is conducted in New Zealand with a target of 300 patients (40% with Māori or Pacific ancestry) eligible if aged ≥18 and ≤80 years, with T2D for more than 1 year, on stable doses of metformin and/or sulfonylurea for at least 3 months, with HbA1c between 59 and 110 mmol/mol inclusive. Participants are assigned to complete 4 months of vildagliptin 50 mg per day or pioglitazone 30 mg per day, followed by 4 months of the other medications in randomly allocated sequences. Participant characteristics, including ethnicity, obesity, lipid profile and candidate genotypes are collected at baseline. Primary outcome variable is on treatment HbA1c. Secondary outcomes include weight change, frequency of side effects and patient preference., Ethics and Dissemination: Ethical approval of the trial has been obtained from the New Zealand Health and Disability Ethics Committee (18/STH/242). The trial commenced in February 2019 and recruitment is expected to be completed by March 2020. Results will be reported in articles submitted to peer-reviewed journals, as well as in presentations at national and international meetings., Trial Registration Number: ACTRN12618001907235., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)