'Next Generation Youth Well-being Study:' understanding the health and social well-being trajectories of Australian Aboriginal adolescents aged 10-24 years: study protocol

INTRODUCTION:Australian Aboriginal and/or Torres Strait Islander (hereafter referred to as 'Aboriginal') adolescents (10-24 years) experience multiple challenges to their health and well-being. However, limited evidence is available on factors influencing their health trajectories. Given the needs of this group, the young age profile of the Aboriginal population and the long-term implications of issues during adolescence, reliable longitudinal data are needed. METHODS AND ANALYSIS:The 'Next Generation: Youth Well-being Study' is a mixed-methods cohort study aiming to recruit 2250 Aboriginal adolescents aged 10-24 years from rural, remote and urban communities in Central Australia, Western Australia and New South Wales. The study assesses overall health and well-being and consists of two phases. During phase 1, we qualitatively explored the meaning of health and well-being for adolescents and accessibility of health services. During phase 2, participants are being recruited into a longitudinal cohort. Recruitment is occurring mainly through community networks and connections. At baseline, participants complete a comprehensive survey and undertake an extensive age relevant clinical assessment. Survey and clinical data will be linked to various databases including those relating to health services; medication; immunisation; hospitalisations and emergency department presentations; death registrations; education; child protection and corrective services. Participants will receive follow-up surveys approximately 2 years after their baseline visit. The 'Next Generation' study will fill important evidence gaps by providing longitudinal data on the health and social well-being of Aboriginal adolescents supplemented with narratives from participants to provide context. ETHICS AND DISSEMINATION:Ethics approvals have been sought and granted. Along with peer-reviewed publications and policy briefs, research findings will be disseminated via reports, booklets and other formats that will be most useful and informative to the participants and community organisations.Lina Gubhaju, Emily Banks, James Ward, Catherine D, Este, Rebecca Ivers ... Peter Azzopardi ... et al. (on behalf of the, Next Generation, investigator team

Impact of an integrated diabetes service involving specialist outreach and primary health care on risk factors for micro- and macrovascular diabetes complications in remote Indigenous communities in Australia

© 2018 National Rural Health Alliance Ltd. Objective: To determine the impact of an integrated diabetes service involving specialist outreach and primary health care teams on risk factors for micro- and macrovascular diabetes complications in three remote Indigenous Australian communities over a 12-month period. Design: Quantitative, retrospective evaluation. Setting: Primary health care clinics in remote Indigenous communities in Australia. Participants: One-hundred-and-twenty-four adults (including 123 Indigenous Australians; 76.6% female) with diabetes living in remote communities. Main outcome measures: Glycosylated haemoglobin, lipid profile, estimated glomerular filtration rate, urinary albumin : creatinine ratio and blood pressure. Results: Diabetes prevalence in the three communities was high, at 32.8%. A total of 124 patients reviewed by the outreach service had a median consultation rate of 1.0 by an endocrinologist and 0.9 by a diabetes nurse educator over the 12-month period. Diabetes care plans were made in collaboration with local primary health care services, which also provided patients with diabetes care between outreach team visits. A significant reduction was seen in median (interquartile range) glycosylated haemoglobin from baseline to 12 months. Median (interquartile range) total cholesterol was also reduced. The number of patients prescribed glucagon-like peptide-1 analogues and dipeptidyl peptidase-4 inhibitors increased over the 12 months and an increase in the number of patients prescribed insulin trended towards statistical significance. Conclusion: A collaborative health care approach to deliver diabetes care to remote Indigenous Australian communities was associated with an improvement in glycosylated haemoglobin and total cholesterol, both important risk factors, respectively, for micro- and macrovascular diabetes complications

Preconception care for diabetic women for improving maternal and fetal outcomes : a systematic review and meta-analysis

Background Preexisting diabetes mellitus is associated with increased risk for maternal and fetal adverse outcomes. Despite improvement in the access and quality of antenatal care recent population based studies demonstrating increased congenital abnormalities and perinatal mortality in diabetic mothers as compared to the background population. This systematic review was carried out to evaluate the effectiveness and safety of preconception care in improving maternal and fetal outcomes for women with preexisting diabetes mellitus. Methods We searched the following databases, MEDLINE, EMBASE, WEB OF SCIENCE, Cochrane Library, including the CENTRAL register of controlled trials and CINAHL up to December 2009, without language restriction, for any preconception care aiming at health promotion, glycemic control and screening and treatment of diabetes complications in women of reproductive age group with type I or type II diabetes. Study design were trials (randomized and non-randomized), cohort and case-control studies. Of the 1612 title scanned 44 full papers were retrieved of those 24 were included in this review. Twelve cohort studies at low and medium risk of bias, with 2502 women, were included in the meta-analysis. Results Meta-analysis suggested that preconception care is effective in reducing congenital malformation, RR 0.25 (95% CI 0.15-0.42), NNT17 (95% CI 14-24), preterm delivery, RR 0.70 (95% CI 0.55-0.90), NNT = 8 (95% CI 5-23) and perinatal mortality RR 0.35 (95% CI 0.15-0.82), NNT = 32 (95% CI 19-109). Preconception care lowers HbA1c in the first trimester of pregnancy by an average of 2.43% (95% CI 2.27-2.58). Women who received preconception care booked earlier for antenatal care by an average of 1.32 weeks (95% CI 1.23-1.40). Conclusion Preconception care is effective in reducing diabetes related congenital malformations, preterm delivery and maternal hyperglycemia in the first trimester of pregnancy

Familial vasopressin-sensitive ACTH-independent macronodular adrenal hyperplasia (VPs-AIMAH): clinical studies of three kindreads

Cushing's syndrome due to familial ACTH-independent macronodular adrenal hyperplasia (AIMAH) has been reported in small kindreds. In vasopressin-sensitive AIMAH (VPs-AIMAH), VP stimulates an aberrant, ACTH-independent increase in cortisol. The aims of this study were to (i) delineate the preclinical phenotype of VPs-AIMAH in a three-generation kindred (AIMAH-01) and two smaller kindreds (AIMAH-02 and AIMAH-03) and (ii) investigate the aetiology of VP sensitivity in AIMAH-01. Design: Clinical studies of three kindreds for adrenal tumours or early Cushing's and molecular studies of adrenal tumours (AIMAH-01). Patients: Thirty-three individuals, from three kindreds, were screened for perturbations of the hypothalamic-pituitary-adrenal axis or adrenal tumours. Measurements: Patients underwent clinical, biochemical and adrenal imaging investigations. Evaluation included low-dose (1 IU/70 kg) VP stimulation. Adrenal VP receptor (AVPR1A, AVPR1B, AVPR2) expression (AIMAH-01) was assessed using RT-PCR and immunohistochemistry (IHC). IHC for VP was also performed. Results: AIMAH-01 had three siblings with Cushing's, and four individuals with suppressed ACTH/aberrant VP responses and/or adrenal nodules. In AIMAH-02, a father and son were affected. AIMAH-03 had three siblings with Cushing's. RT-PCR showed adrenal overexpression of AVPR1A and AVPR1B. IHC detected AVPR1A. The adrenal tumour from one patient also stained weakly for VP and AVPR2. Conclusion:  Adrenal nodules, suppressed ACTH and increased VP sensitivity may represent preclinical disease, allowing early detection, and treatment, of affected individuals. In AIMAH-01, increased VP sensitivity may be due to adrenal VP receptor overexpression. In these kindreds, VPs-AIMAH is familial, and autosomal dominant inheritance is most likely.Gagliardi, Lucia; Hotu, Cheri; Casey, Graeme; Braund, Wilton J.; Ling, King-Hwa; Dodd, Thomas; Manavis, James; Devitt, Peter G.; Cutfield, Richard; Rudzki, Zbigniew; Scott, Hamish S.; Torpy, David J

ARMC5 mutations are common in familial bilateral macronodular adrenal hyperplasia.

CONTEXT: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of adrenal Cushing's syndrome. Familial cases have been reported, but at the time we conducted this study, the genetic basis of BMAH was unknown. Recently, germline variants of armadillo repeat containing 5 (ARMC5) in patients with isolated BMAH and somatic, second-hit mutations in tumor nodules, were identified. OBJECTIVE: Our objective was to identify the genetic basis of familial BMAH. DESIGN: We performed whole exome capture and sequencing of 2 affected individuals from each of 4 BMAH families (BMAH-01, BMAH-02, BMAH-03, and BMAH-05). Based on clinical evaluation, there were 7, 3, 3, and 4 affected individuals in these families, respectively. Sanger sequencing of ARMC5 was performed in 1 other BMAH kindred, BMAH-06. RESULTS: Exome sequencing identified novel variants Chr16:g.31477540, c.2139delT, p.(Thr715Leufs*1) (BMAH-02) and Chr16:g.31473811, c.943C→T, p.(Arg315Trp) (BMAH-03) in ARMC5 (GRch37/hg19), validated by Sanger sequencing. BMAH-01 had a recently reported mutation Chr16:g.31476121, c.1777C→T, p.(Arg593Trp). Sanger sequencing of ARMC5 in BMAH-06 identified a previously reported mutation, Chr16:g. 31473688; c.799C→T, p.(Arg267*). The genetic basis of BMAH in BMAH-05 was not identified. CONCLUSIONS: Our studies have detected ARMC5 mutations in 4 of 5 BMAH families tested, confirming that these mutations are a frequent cause of BMAH. Two of the 4 families had novel mutations, indicating allelic heterogeneity. Preclinical evaluation did not predict mutation status. The ARMC5-negative family had unusual prominent hyperaldosteronism. Further studies are needed to determine the penetrance of BMAH in ARMC5 mutation-positive relatives of affected patients, the practical utility of genetic screening and genotype-phenotype correlations

'Next Generation Youth Well-being Study:' understanding the health and social well-being trajectories of Australian Aboriginal adolescents aged 10-24 years: study protocol

INTRODUCTION: Australian Aboriginal and/or Torres Strait Islander (hereafter referred to as 'Aboriginal') adolescents (10-24 years) experience multiple challenges to their health and well-being. However, limited evidence is available on factors influencing their health trajectories. Given the needs of this group, the young age profile of the Aboriginal population and the long-term implications of issues during adolescence, reliable longitudinal data are needed. METHODS AND ANALYSIS: The 'Next Generation: Youth Well-being Study' is a mixed-methods cohort study aiming to recruit 2250 Aboriginal adolescents aged 10-24 years from rural, remote and urban communities in Central Australia, Western Australia and New South Wales. The study assesses overall health and well-being and consists of two phases. During phase 1, we qualitatively explored the meaning of health and well-being for adolescents and accessibility of health services. During phase 2, participants are being recruited into a longitudinal cohort. Recruitment is occurring mainly through community networks and connections. At baseline, participants complete a comprehensive survey and undertake an extensive age relevant clinical assessment. Survey and clinical data will be linked to various databases including those relating to health services; medication; immunisation; hospitalisations and emergency department presentations; death registrations; education; child protection and corrective services. Participants will receive follow-up surveys approximately 2 years after their baseline visit. The 'Next Generation' study will fill important evidence gaps by providing longitudinal data on the health and social well-being of Aboriginal adolescents supplemented with narratives from participants to provide context. ETHICS AND DISSEMINATION: Ethics approvals have been sought and granted. Along with peer-reviewed publications and policy briefs, research findings will be disseminated via reports, booklets and other formats that will be most useful and informative to the participants and community organisations

Clinical features of patients hospitalised with COVID-19 from February to October 2020, during the early waves of the pandemic in New Zealand

Aim: As New Zealand transitions towards endemic SARS-CoV-2, understanding patient factors predicting severity, as well as hospital resourcing requirements will be essential for future planning. Methods: We retrospectively enrolled patients hospitalised with COVID-19 from 26 February to 5 October 2020 as part of the COVID-19 HospitalisEd Patient SeverIty Observational Study NZ (COHESION). Data on demographics, clinical course and outcomes were collected and analysed as a descriptive case series. Results: Eighty-four patients were identified across eight district health boards. Forty-one (49%) were male. The median age was 58 years [IQR: 41.7–70.3 years]. By ethnicity, hospitalisations included 38 NZ European (45%), 19 Pasifika (23%), 13 Māori (15%), 12 Asian (14%) and 2 Other (2%). Pre-existing co-morbidities included hypertension (26/82, 32%), obesity (16/66, 24%) and diabetes (18/81, 22%). The median length of stay was four days [IQR: 2–15 days]. Twelve patients (12/83, 14%) were admitted to an intensive care unit or high dependency unit (ICU/HDU). Ten (10/83, 12%) patients died in hospital of whom seven (70%) were not admitted to ICU/HDU; the median age at death was 83 years. Conclusion: Despite initially low case numbers in New Zealand during 2020, hospitalisation with COVID-19 was associated with a high mortality and hospital resource requirements