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Objective. Microvascular complications increase the risk of cardiovascular disease and premature death in adults with type 1 diabetes. We examined the association between microvascular complications during adolescence, including cardiac autonomic nerve dysfunction and subsequent mortality. Research Design and Methods. We undertook data linkage with the Australian National Death Index in a cohort of 409 adolescents (diagnosed between 1973 and 1993), 48% male, median age at final complications assessment 17.4 years (interquartile range: 16.0–18.9), followed longitudinally for median 22.3 years (21.0–23.4) from diagnosis. Generalized estimating equations (GEE) were used to examine associations between mortality and adolescent complications. Mortality risk was calculated as standardized mortality ratio (SMR). Results. At final adolescent visit, 20% had CAN abnormality, 30% abnormal pupillary response, 20% albuminuria, 40% early elevation of albumin excretion rate (AER) and 45% retinopathy. Data linkage 8–13 years later showed 14 were deceased (3% of cohort), 57% male, median age 28.3 years (24.8–32.9). Acute or chronic diabetes complications accounted for 25% of deaths. In multivariable GEE, elevated AER (OR 4.54, 1.23–16.80, p = 0.030), pupillary abnormality (OR 4.27, 1.20–15.22, p = 0.023), systolic blood pressure SDS (OR 2.17, 1.26–3.74, p = 0.005) and CAN (OR 4.65, 1.03–21.0, p = 0.045) predicted mortality. HbA1c was not significant. SMR was 2.5 (1.4–4.2) and was higher in females (SMR 3.5, 1.3–7.8) but not in males (SMR 2.1, 0.9–4.0). Conclusion. Mortality in young adults with type 1 diabetes is predicted by subclinical markers of autonomic neuropathy and elevated AER during adolescence, but not glycemia. Mortality was over twice that of the background population in females but not in males. [ABSTRACT FROM AUTHOR]

Background: Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations. Methods: Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort's distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial's intervention was targeted (national). Results: Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p < 0.001) were over- and under-represented relative to the regional reference, while the UK featured higher regional and national SES bias with over-representation and under-representation from the least-deprived and most-deprived quintiles (p < 0.0001). Conclusions: Significant national differences in trial participation of low SES participants were observed, highlighting limitations in access to clinical research and the importance of reporting sociodemographic representation in diabetes clinical trials. Trial registration: NCT01581476. Registered on 20 April 2012. [ABSTRACT FROM AUTHOR]

Objective: To examine the prevalence, time trends, and risk factors of diabetic retinopathy (DR) among youth with type 1 diabetes (T1D) from 11 countries (Australia, Austria, Denmark, England, Germany, Italy, Luxemburg, Netherlands, Slovenia, United States, and Wales). Subjects and Methods: Data on individuals aged 10–21 years with T1D for >1 year during the period 2000–2020 were analyzed. We used a cross‐sectional design using the most recent year of visit to investigate the time trend. For datasets with longitudinal data, we aggregated the variables per participant and observational year, using data of the most recent year to take the longest observation period into account. DR screening was performed through quality assured national screening programs. Multiple logistic regression models adjusted for the year of the eye examination, age, gender, minority status, and duration of T1D were used to evaluate clinical characteristics and the risk of DR. Results: Data from 156,090 individuals (47.1% female, median age 15.7 years, median duration of diabetes 5.2 years) were included. Overall, the unadjusted prevalence of any DR was 5.8%, varying from 0.0% (0/276) to 16.2% between countries. The probability of DR increased with longer disease duration (aORper‐1‐year‐increase = 1.04, 95% CI: 1.03–1.04, p < 0.0001), and decreased over time (aORper‐1‐year‐increase = 0.99, 95% CI: 0.98–1.00, p = 0.0093). Evaluating possible modifiable risk factors in the exploratory analysis, the probability of DR increased with higher HbA1c (aORper‐1‐mmol/mol‐increase‐in‐HbA1c = 1.03, 95% CI: 1.03–1.03, p < 0.0001) and was higher among individuals with hypertension (aOR = 1.24, 95% CI: 1.11–1.38, p < 0.0001) and smokers (aOR = 1.30, 95% CI: 1.17–1.44, p < 0.0001). Conclusions: The prevalence of DR in this large cohort of youth with T1D varied among countries, increased with diabetes duration, decreased over time, and was associated with higher HbA1c, hypertension, and smoking. [ABSTRACT FROM AUTHOR]

Objective: Cardiovascular autonomic neuropathy (CAN) is an overlooked but common and serious diabetes complication. We examined CAN in youth with diabetes and associations with cardiovascular risk factors. Research Design and Methods: This was a prospective cohort of youth aged <20 years with type 2 or type 1 diabetes (n = 66/1153, median age 15.4/16.5 years, duration 1.7/8.0 years), assessed between 2009 and 2020. CAN was defined as ≥2 abnormal heart rate variability measures across time, geometric, and frequency domains. Obesity was defined as BMI ≥ 95th percentile and severe obesity as ≥120% of 95th percentile. Multivariable generalized estimating equations (GEE) were used to examine putative risk factors for CAN, including diabetes type, obesity, and HbA1c. Results: At most recent assessment, youth with type 2 versus type 1 diabetes had median: HbA1c 7.1% (54 mmol/mol) versus 8.7% (72 mmol/mol) and BMI SDS (2.0 vs. 0.7); frequency of CAN (47% vs. 27%), peripheral nerve abnormality (47% vs. 25%), hypertension (29% vs. 12%), albuminuria (21% vs. 3%), and severe obesity (35% vs. 2%). In multivariable GEE, CAN was associated with type 2 diabetes: Odds Ratio 2.53, 95% CI 1.46, 4.38, p = 0.001, higher BMI SDS: 1.49, 95% CI 1.29, 1.73, p < 0.0001, and obesity: 2.09, 95% CI 1.57, 2.78, p < 0.0001. Conclusions: Youth with type 2 diabetes have a higher frequency of CAN, peripheral nerve abnormality, hypertension, albuminuria and severe obesity despite shorter diabetes duration and younger age. Our findings highlight the importance of targeting modifiable risk factors to prevent cardiovascular disease in youth with diabetes. [ABSTRACT FROM AUTHOR]

Objective: The relationship between retinal vascular calibres (RVCs) and diabetic neuropathy is unclear. We investigated associations between RVCs and sensory nerve abnormality in adolescents with type 1 diabetes. Research design and methods: In a prospective longitudinal study of 889 adolescents with type 1 diabetes with baseline mean (±SD) age 14.1 ± 1.5 years and HbA1c IFCC 69.4 ± 14.1 mmol/mol (8.6 ± 1.3%), RVCs were assessed from baseline retinal photographs: 'central zone' calibres, summarized as central retinal arteriolar (CRAE) and venular equivalents (CRVE) and 'extended zone' calibres: mean width of arterioles (MWa) and venules (MWv). Sensory nerve abnormality was defined as at least one abnormal sensory quantitative testing from two thermal and two vibration threshold tests measured at foot every 1–2 years. Associations between baseline RVC and sensory nerve function were examined using generalized estimating equations and cumulative risk by Cox regression analyses. Results: During a median study follow‐up of 6.2 [IQR 3.7–10.4] years, sensory nerve abnormality was found in 27% of adolescents. Narrower extended zone calibre quartiles but not CRAE or CRVE quartiles were independently associated with sensory nerve abnormality: MWa (Q1 vs. Q2‐4: OR 1.35 (95% CI 1.02, 1.61) and MWv (Q1 vs. Q2‐4: 1.31 (1.03, 1.7)), after adjusting for HbA1c, duration and blood pressure. Similarly, in Cox regression, the narrowest quartiles were associated with sensory nerve abnormality: MWa hazard ratio (HR) 1.5 (1.3, 1.8) and MWv 1.6 (1.4, 1.9). Conclusions: Narrower extended zone retinal calibres were associated with sensory nerve abnormality in adolescents with type 1 diabetes and may present useful biomarkers to understand the pathophysiology of neuropathy. [ABSTRACT FROM AUTHOR]

Objectives: To assess the clinical and demographic characteristics of children and adolescents across Australia and New Zealand (NZ) with type 2 diabetes. Methods: We performed a descriptive audit of data prospectively reported to the Australasian Diabetes Data Network (ADDN) registry. Data were collected from six tertiary pediatric diabetes centers across Australia (New South Wales, Queensland, South Australia, Western Australia, and Victoria) and NZ (Auckland). Children and adolescents diagnosed with type 2 diabetes aged ≤ 18 years with data reported to ADDN between 2012 and 2017 were included. Age, sex, ethnicity, HbA1c, blood pressure, BMI, waist circumference and lipid profile at first visit were assessed. Results: There were 269 cases of type 2 diabetes in youth reported to ADDN between 2012 and 2017. The most common ethnicities were Indigenous Australian in 56/243 (23%) and NZ Maori or Pacifica in 47 (19%). Median age at diagnosis was 13.7 years and 94% of participants were overweight or obese. Indigenous Australian and Maori/Pacifica children were younger at diagnosis compared with nonindigenous children: median 13.3 years (indigenous Australian); 13.1 years (Maori/Pacifica); 14.1 years (nonindigenous), p = 0.005. HbA1c was higher in indigenous Australian (9.4%) and Maori/Pacifica youth (7.8%) compared with nonindigenous (6.7%) p < 0.001. BMI‐SDS was higher in Maori/Pacifica youth (2.3) compared with indigenous Australian (2.1) and nonindigenous (2.2) p = 0.011. Conclusions: Indigenous Australian and Maori/Pacifica youth in ADDN were younger and had worse glycaemic control at diagnosis of type 2 diabetes. Our findings underscore the need to consider targeted and earlier screening in these "high‐risk" populations. [ABSTRACT FROM AUTHOR]

ABSTRACT World population and industrialization have increased significantly, leading to an increase in global energy demand, mainly relying on fossil fuels. Use of alternative energy sources such as wind, hydro and solar has been steadily increasing. Australia is a vast continent which receives an average 58 million PJ of energy from the sun annually. Given this resource potential, one could envisage construction of massive solar farms to help meet energy demands. If such constructions went ahead, their potential benefits/impacts on the climate over and surrounding the solar arrays would need to be investigated. Here, we study the potential climatic impacts over and in the environment surrounding massive hypothetical solar sites across Australia using a global stretched grid atmospheric model. The solar farms are represented by modelling the effects of perturbing surface albedo and surface roughness. The sensitivity experiments incorporate different combinations of surface albedos, shapes and locations of the solar farms, with a focus on the summer season. Our study suggests that depending on array sizes, locations, orientations and surface albedo (potentially increased by means of highly reflective in-fill material), the climate over solar arrays could be modified significantly. Over the arrays with positive albedo perturbation, rainfall would decrease by around 30-70%, and daytime maximum air temperatures would decrease up to 10 °C. In addition, solar irradiance would increase by around 5-20%, which combined with the air temperature cooling, would lead to an enhanced solar power yield up to 25%. [ABSTRACT FROM AUTHOR]

Objective: To examine trends in microvascular complications in adolescents with type 1 diabetes between 1990 and 2009 in Sydney, Australia.Research Design and Methods: We used analysis of complications in 1,604 adolescents (54% female, aged 12-20 years, median duration 8.6 years), stratified by four time periods using Generalized Estimation Equations as follows: T1 (1990-1994), T2 (1995-1999), T3 (2000-2004), and T4 (2005-2009). Early retinopathy was detected using seven-field fundal photography, albumin excretion rate (AER) using timed overnight urine collections, and albumin-to-creatinine ratio (ACR) and peripheral nerve function using thermal and vibration threshold.Results: Retinopathy declined (53, 38, 23, and 12%; P < 0.001), as did borderline elevation of AER/ACR (45, 30, 26, and 30%; P < 0.001) and microalbuminuria (8, 4, 3, and 3%; P = 0.006). Multiple daily injections (MDI)/continuous subcutaneous insulin infusion (CSII) use increased (17, 54, 75, and 88%; P < 0.001), median HbA(1c) decreased (9.1, 8.9, 8.5, and 8.5%; P < 0.001), and severe hypoglycemia was unchanged (6, 8, 10, and 7%; P = 0.272). Retinopathy was associated with diabetes duration (odds ratio [OR] 1.12 [95% CI 1.08-1.17]), age (1.13 [1.06-1.20]), HbA(1c) (1.16 [1.08-1.25]), systolic blood pressure (BP) SDS (1.31 [1.16-1.48]), socioeconomic disadvantage (1.42 [1.04-1.95]), and 1 to 2 injections per day (vs. MDI/CSII; 1.35 [1.05-1.73]); borderline AER/ACR with male sex (1.32 [1.02-1.70]), age (1.19 [1.12-1.26]), HbA(1c) (1.18 [1.08-1.29]), weight SDS (1.31 [1.21-1.53]), insulin dose per kilograms (1.64 [1.13-2.39]), 1 to 2 injections per day (1.41 [1.08-1.84]), and socioeconomic disadvantage (1.68 [1.23-2.31]); and microalbuminuria with age (1.14 [1.01-1.29]), HbA(1c) (1.20 [1.05-1.37]), diastolic BP SDS (1.76 [1.26-2.46]), and 1 to 2 injections per day (1.95 [1.11-3.41]).Conclusions: The decline in retinopathy supports contemporary guidelines that recommend lower glycemic targets and use of MDI/CSII in children and adolescents with type 1 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine the association between retinal vascular geometry and subsequent development of incident retinopathy in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS--A prospective cohort study of 736 people with type 1 diabetes aged 12 to 20 years, retinopathy-free at baseline, attending an Australian tertiary care hospital. Retinopathy was determined from seven-field retinal photographs according to the modified Airlie House Classification. Retinal vascular geometry, including length/diameter ratio (LDR) and simple tortuosity (ST), was quantified in baseline retinal photographs. Generalized estimating equations were used to determine risk of retinopathy associated with baseline LDR and ST, adjusting for other factors. RESULTS---After a median 3.8 (interquartile range 2.4-6.1) years of follow-up, incident retinopathy developed in 287 of 736 (39%). In multivariate analysis, lower arteriolar LDR (odds ratio 1.8 [95% CI 1.2-2.6]; 1st vs. 4th quartile) and greater arteriolar ST (1.5 [1.0-2.2]; 4th vs. 1st quartile) predicted incident retinopathy after adjusting for diabetes duration, sex, A1C, blood pressure, total cholesterol, and BMI. In subgroup analysis by sex, LDR predicted incident retinopathy in male and female participants (2.1 [1.1-4.0] and 1.7 [1.1-2.7]; 1st vs. 4th quartiles, respectively) and greater arteriolar ST predicted incident retinopathy in male participants (2.4 [1.1-4.4]; 4th vs. 1st quartile) only. CONCLUSIONS--Lower arteriolar LDR and greater ST were independently associated with incident retinopathy in young people with type 1 diabetes. These vascular geometry measures may serve as risk markers for diabetic retinopathy and provide insights into the early structural changes in diabetic microvascular complications. [ABSTRACT FROM AUTHOR]

The article focuses on a research in Australia which examines the effectiveness of percentile charts to monitor the physical development of children and adolescents with diabetes. The study showed that there would be no role for human growth hormone therapy in poorly growing child with diabetes, unless it is associated with documented growth hormone deficiency. Moreover, oedema complications due to insulin therapy would be determined during the establishment of improved glycemic control.

OBJECTIVE -- In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme. PON1 polymorphisms have been associated with susceptibility to macro- and microvascular complications. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants, p.Leu54Met, p.Gln192Arg, and c.-107C>T, in type 1 diabetes. RESEARCH DESIGN AND METHODS -- This was a cross-sectional study of 331 adolescents with type 1 diabetes (162 male and 169 female). PFT was assessed by ultrasound, PON1 was assessed by genotyping with PCR and restriction fragment-length polymorphism, and serum PON1 activity was assessed by rates of hydrolysis of paraoxon and phenylacetate. RESULTS -- Median (interquartile range) age was 15.4 (13.5-17.3) years, and diabetes duration was 7.6 (4.9-10.6) years. The distribution of p.Leu54Met genotypes was LL 135 (40.8%), ML 149 (45%), and MM 47 (14.2%). PFT was abnormal (>1.7 mm) in 159 adolescents (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL versus MM p.Leu54Met polymorphism (odds ratio 3.84 [95% CI 1.49-9.82], P = 0.005); BMI (percentile) (1.02 [1.01-1.03], P = 0.007); systolic blood pressure (percentile) (1.01 [1.00-1.02], P = 0.03); and male sex (3.29 [1.98-5.46], P < 0.001). CONCLUSIONS -- Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with a reduced risk of abnormal PFT. [ABSTRACT FROM AUTHOR]

Provides information on a study which examined whether socioeconomic disadvantage or urban/rural location affect metabolic control in Australia. How social disadvantage was assessed; Comparison between rural children and city-based children; Analysis of the incidence of severe hypoglycemia.

Summary: Six methods of downscaling GCM simulations to multi-site daily precipitation were applied to a set of 30 rain gauges located within South-Eastern Australia. The methods were tested at reproducing a range of statistics important within hydrological studies including inter-annual variability and spatial coherency using both NCEP/NCAR reanalysis and GCM predictors, thus testing the validity of GCM downscaled predictions. The methods evaluated, all having found application in Australia previously, are: (1) the dynamical downscaling Conformal-Cubic Atmospheric Model (CCAM) of ; the historical data based (2) Scaling method applied by and (3) Analogue method of ; and three stochastic methods, (4) the GLIMCLIM (Generalised Linear Model for daily Climate time series) software package (), (5) the Non-homogeneous Hidden Markov Model (NHMM) of Charles et al. (1999), and (6) the modified Markov model–kernel probability density estimation (MMM–KDE) downscaling technique of . The results showed that the simple Scaling approach provided relatively robust results for a range of statistics when GCM forcing data was used, and was therefore recommended for regional water availability and planning studies (subject to certain limitations as mentioned in conclusion section). The stochastic methods better capture changes to a fuller range of rainfall statistics and are recommended for detailed catchment modelling studies. In particular, the stochastic methods show better results for daily extreme rainfall (e.g. flooding/low flow) as the simulations are not based purely on temporal/spatial rainfall patterns observed in the past, and a hybrid GLIMCLIM occurrence-KDE amounts model is recommended based on performance for individual statistics. For GCM downscaled simulations, biases in annual mean and standard deviation of ±5% and −30% were observed typically, and no single model performed well over all timescales/statistics, suggesting that the user beware of model limitations when applying downscaling methods for various purposes. A brief demonstration of predictor biases is presented, highlighting that biases observed in GCM predictors can cause poorer performance during GCM validation, and that investigation of these biases should inform choice of GCMs, GCM predictors, and the downscaling methods that use them. [Copyright &y& Elsevier]

Background: Hepatocellular carcinoma (HCC) recurrence following surgical resection remains a significant clinical challenge, necessitating reliable predictive models to guide personalised interventions. In this study, we sought to harness the power of artificial intelligence (AI) to develop a robust predictive model for HCC recurrence using comprehensive clinical datasets., Methods: Leveraging data from 958 patients across multiple centres in Australia and Hong Kong, we employed a multilayer perceptron (MLP) as the optimal classifier for model generation., Results: Through rigorous internal cross-validation, including a cohort from the Chinese University of Hong Kong (CUHK), our AI model successfully identified specific pre-surgical risk factors associated with HCC recurrence. These factors encompassed hepatic synthetic function, liver disease aetiology, ethnicity and modifiable metabolic risk factors, collectively contributing to the predictive synergy of our model. Notably, our model exhibited high accuracy during cross-validation (.857 ± .023) and testing on the CUHK cohort (.835), with a notable degree of confidence in predicting HCC recurrence within accurately classified patient cohorts. To facilitate clinical application, we developed an online AI digital tool capable of real-time prediction of HCC recurrence risk, demonstrating acceptable accuracy at the individual patient level., Conclusion: Our findings underscore the potential of AI-driven predictive models in facilitating personalised risk stratification and targeted interventions to mitigate HCC recurrence by identifying modifiable risk factors unique to each patient. This model aims to aid clinicians in devising strategies to disrupt the underlying carcinogenic network driving recurrence., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background: The prevalence of sleep-disordered breathing in children is underestimated due to impediments in detection and diagnosis. Consequently, delayed management may affect the quality of life and the growth and development of a child. Due to their patient demographic, orthodontists are optimally positioned to identify those at risk of sleep-disordered breathing and make referrals for investigation and management. This study aims to determine the prevalence of children at risk of sleep-disordered breathing in an Australian orthodontic population., Methods: A 1-year retrospective study was conducted in an urban Western Australian private orthodontic practice with two branches in similar socioeconomic demographics. The responses of new patients to a modified paediatric sleep questionnaire and standard medical history form were recorded., Results: In 1209 patients (4-18 years), 7.3% were at risk of sleep-disordered breathing. An association between sex and the potential risk of sleep-disordered breathing was found with 11% of males at risk of sleep-disordered breathing compared to 7% of females (P = 0.012)., Conclusions: The relatively high prevalence of children at risk of sleep-disordered breathing presenting for orthodontic care presents an opportunity to identify at-risk individuals through routine use of the paediatric sleep questionnaire. This would facilitate early referral for diagnosis and management of sleep-disordered breathing., (© 2022 The Authors. Australian Dental Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Dental Association.)

Peer support programmes have been shown to facilitate diabetes prevention and improvements in diabetes self-management. Worldwide, few studies have qualitatively evaluated peer support programs in inner-regional (semi-rural) areas, and none involving mixtures of people with and without diabetes. This study researched an inner-regional peer support programme underway over 2 years in Australia. Fifteen participants, including ten peers and five peer support facilitators (PSFs) were interviewed using semi-structured focus group and one-to-one interviews with the aim of understanding their perceptions and experiences of the programme, barriers, and ways of overcoming barriers. Participants were those with and without diabetes. The main themes identified were; benefits of the programme, factors affecting recruitment and retention, challenges and barriers to programme participation, PSF reflections on peer support training, and recommendations to improve the programme. Participants identified increased knowledge of diet, diabetes and complications as key benefits, with greater social support and well-being the main reasons for initial participation. The main challenges for the programme were the lack of wide community engagement before setting up the peer groups, difficulty with peer recruitment and personal difficulties in maintaining a healthy lifestyle. The peer support programme was well received within an inner-regional area and was perceived as useful in providing support and motivation to make lifestyle behavioural changes from shared experiences with peers. Whilst considered beneficial to those with and without diabetes, ways of overcoming identified challenges are required., (© 2022 John Wiley & Sons Ltd.)

Introduction: Type 2 diabetes in young adults (nominally, 18-30 years of age) is a more aggressive condition than that seen in older age, with a greater risk of major morbidity and early mortality. This first Australian consensus statement on the management of type 2 diabetes in young adults considers areas where existing type 2 diabetes guidance, directed mainly towards older adults, may not be appropriate or relevant for the young adult population. Where applicable, recommendations are harmonised with current national guidance for type 2 diabetes in children and adolescents (aged < 18 years). The full statement is available at https://www.diabetessociety.com.au, https://www.adea.com.au and https://www.apeg.org.au., Main Recommendations: Advice is provided on important aspects of care including screening, diabetes type, psychological care, lifestyle, glycaemic targets, pharmacological agents, cardiovascular disease risk management, comorbidity assessment, contraception and pregnancy planning, and patient-centred education. Special considerations for Aboriginal and Torres Strait Islander Australians are highlighted separately., Changes in Management as a Result of This Statement: Management recommendations for young adults, which differ from those for adults, include: ▪screening for diabetes in young adults with overweight or obesity and additional risk factors, including in utero exposure to type 2 diabetes or gestational diabetes mellitus; ▪more stringent glucose targets (glycated haemoglobin ≤ 6.5% [≤ 48 mmol/mol]); ▪in the context of obesity or higher cardio-renal risk, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors are preferred second line agents; ▪β-cell decline is more rapid, so frequent review, early treatment intensification and avoidance of therapeutic inertia are indicated; ▪a blood pressure target of < 130/80 mmHg, as the adult target of ≤ 140/90 mmHg is too high; ▪absolute cardiovascular disease risk calculators are not likely to be accurate in this age group; early statin use should therefore be considered; and ▪a multidisciplinary model of care including an endocrinologist and a certified diabetes educator., (© 2022 AMPCo Pty Ltd.)

Repeated Plasmodium falciparum infections drive the development of clinical immunity to malaria in humans; however, the immunological mechanisms that underpin this response are only partially understood. We investigated the impact of repeated P. falciparum infections on human γδ T cells in the context of natural infection in Malian children and adults, as well as serial controlled human malaria infection (CHMI) of U.S. adults, some of whom became clinically immune to malaria. In contrast to the predominant Vδ2 + T cell population in malaria-naïve Australian individuals, clonally expanded cytotoxic Vδ1 effector T cells were enriched in the γδ T cell compartment of Malian subjects. Malaria-naïve U.S. adults exposed to four sequential CHMIs defined the precise impact of P. falciparum on the γδ T cell repertoire. Specifically, innate-like Vδ2 + T cells exhibited an initial robust polyclonal response to P. falciparum infection that was not sustained with repeated infections, whereas Vδ1 + T cells increased in frequency with repeated infections. Moreover, repeated P. falciparum infection drove waves of clonal selection in the Vδ1 + T cell receptor repertoire that coincided with the differentiation of Vδ1 naïve T cells into cytotoxic Vδ1 effector T cells. Vδ1 + T cells of malaria-exposed Malian and U.S. individuals were licensed for reactivity to P. falciparum parasites in vitro. Together, our study indicates that repeated P. falciparum infection drives the clonal expansion of an adaptive γδ T cell repertoire and establishes a role for Vδ1 + T cells in the human immune response to malaria.

Perioperative ketoacidosis is an important adverse event related to the use of sodium glucose co-transporter 2 inhibitor (SGLT2i). We compared perioperative outcomes in patients on SGLT2i, before and after protocolised pre-operative cessation of the drug. There were no cases of clinically detected diabetic ketoacidosis in the 96 patients included in the study. Withdrawal of SGLT2i did not appear to alter significantly pre-operative glycaemia., (© 2021 Royal Australasian College of Physicians.)

Background: The rural medical workforce internationally suffers from a significant imbalance between male- and female- identifying practitioners. Not only do male doctors outnumber female doctors, but additionally female doctors work fewer hours than their male counterparts. This has health implications for rural communities. In response, In Australia, Rural Clinical Schools (RCSs) are a national training strategy to increase the number of graduates entering the rural medical workforce. It has been observed that RCSs attract a greater number of female students than male students. However, the future work intentions of male versus female RCS students is not known. This paper therefore asked whether male and female RCS students have equivalent intent for future rural practice., Methods: Participants were all students who attended RCSs from 2015 to 2017, who completed an exit survey that gathered data on demographic, experiential and intentional variables. Univariate analyses examined differences between the sexes. A multivariate model was constructed to determine the independent predictors for rural intention., Results: There were 2017 respondents across the 3 years, of whom 937 identified as male, and 1138 identified as female. In univariate analysis, female-identifying students had significantly higher rural intention than male-identifying students. There were no other sex-based differences in age, rural background, overall perception of support, and overall excellence of clinical education whilst in RCS. However, in multivariate analysis, sex was not a significant predictor for rural work intention, whereas older age, rural background, and first preference for RCS were all predictive of increased rural intent, as expected from the literature. There were no differences between male and female students in their perceptions of the overall support and the clinical education provided by RCS., Conclusion: We conclude from this national study that sex is not an independent predictor for future rural work intention among RCS students. Considering the disproportionate number of female students entering RCS, this is reassuring for ultimately achieving rural workforce gender equity.

Objectives: Only a fraction of youth meet established targets for glycemic control; many experience deteriorating control over time. We compared trajectories of hemoglobin A1c (HbA1c) among youth from three trans-continental type 1 diabetes (T1D) registries and identified clinical variables associated with the odds of following increasing vs stable trajectories., Research Design and Methods: Analyses included longitudinal data from 15 897 individuals age 8 to 18 with T1D for at least 2 years and HbA1c measurements in at least 5 years during the observation period. Cohorts were selected from Australasian Diabetes Data Network (ADDN; Australia), German/Austrian/Luxembourgian Diabetes-Patienten-Verlaufsdokumentation initiative (DPV; Germany/Austria/Luxembourga), and the T1D Exchange Clinic Network (T1DX; US) clinic registries. Group-based trajectory modeling and multivariable logistic regression identified unique HbA1c trajectories and their predictors., Results: Five heterogeneous trajectories of glycemic control in each registry were identified: low, intermediate, high stable; intermediate and high increasing. The overall HbA1c level for each trajectory group tended to be lowest in the DPV, higher in the ADDN, and highest in the T1DX. The absolute level of HbA1c and the proportion of individuals within each trajectory varied across registries: 17% to 22% of individuals followed an increasing trajectory. Compared with maintaining a stable trajectory, following an increasing trajectory was significantly associated with ethnic minority status, lower height z-score, higher BMI z-score, insulin injection therapy, and the occurrence of severe hypoglycemia; however, these factors were not consistent across the three registries., Conclusions: We report the first multinational registry-based comparison of glycemic control trajectories among youth with T1D from three continents and identify possible targets for intervention in those at risk of an increasing HbA1c trajectory., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Children with type 1 diabetes (T1D) are at risk of diabetic ketoacidosis (DKA) at T1D diagnosis and/or subsequently., Objective: The objective is to determine the incidence and prevalence of T1D by the presence of DKA and identify the characteristics of subsequent DKA episodes., Subjects: The study population included all children aged <15 years with T1D during a hospital/day-stay admission in New South Wales, Australia, from 1 January 2001 to 31 December 2013. T1D and DKA were identified using International Classification of Diseases Australian Modification codes., Methods: Data sources included routinely collected longitudinally linked population hospitalization and birth records. Chi-squared analyses, logistic, and multinomial regression were used to determine the association between child characteristics and admissions with and without DKA., Results: The point prevalence of T1D among 0-14-year olds on 31 December 2013 was 144.2 per 100 000. For children aged 0-12 years, the incidence of T1D was 16.3 per 100 000 child-years. One-third had DKA at T1D diagnosis and were more likely to be readmitted with DKA than those without DKA at T1D diagnosis. Children with more than one readmission for DKA were more likely to be female, reside in an inner regional area or an area of socioeconomic disadvantage, and be Australian-born. Among all hospitalizations of children with T1D, those with DKA were more likely to be aged 10-14 years, require intensive care, have longer length of stay, and admitted outside school days., Conclusion: Routinely collected administrative health data are a reliable source to monitor incidence and health service use of childhood T1D. Children at risk of repeated DKA, particularly females, adolescents, and those from inner regional or socioeconomically disadvantaged areas, should be targeted during education and follow-up., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/aim: The aim of the current study was to review drug harms as they occur in Australia using the Multi-criteria Decision Analysis (MCDA) methodology adopted in earlier studies in other jurisdictions., Method: A facilitated workshop with 25 experts from across Australia, was held to score 22 drugs on 16 criteria: 9 related to harms that a drug produces in the individual and 7 to harms to others. Participants were guided by facilitators through the methodology and principles of MCDA. In open discussion, each drug was scored on each criterion. The criteria were then weighted using a process of swing weighting. Scoring was captured in MCDA software tool., Results: MCDA modelling showed the most harmful substances to users were fentanyls (part score 50), heroin (part score 45) and crystal methamphetamine (part score 42). The most harmful substances to others were alcohol (part score 41), crystal methamphetamine (part score 24) and cigarettes/tobacco (part score 14). Overall, alcohol was the most harmful drug when harm to users and harm to others was combined. A supplementary analysis took into consideration the prevalence of each substance in Australia. Alcohol was again ranked the most harmful substance overall, followed by cigarettes, crystal methamphetamine, cannabis, heroin and pharmaceutical opioids., Conclusions: The results of this study make an important contribution to the emerging international picture of drug harms. They highlight the persistent and pervasive harms caused by alcohol. Policy implications and recommendations are discussed. Policies to reduce harm from alcohol and methamphetamine should be a priority.

Background: Intensive insulin regimens are now the mainstay of modern, type 1 diabetes mellitus management. Insulin pumps (CSII) are a key technique used. Although there has been considerable study of outcomes, there are few recent data on CSII-associated adverse events (AEs) and their incidence and characteristics., Subjects and Methods: Phone calls to our 24-h diabetes support service were screened for CSII-associated AEs. Phone interviews were conducted with the parent/patient, within 96 h of the event. Interviews explored AE characteristics and the role of the user, as well as questions relating to outcome and the impact to the family and patient. Comparisons were made with clinic CSII patients not reporting an AE., Results: Over a 16-week study period, 50 confirmed AEs occurred in 45 of 405 (11.1%) patients. This was annualized to an AE incidence of 40 AEs/100 person-years. Pump malfunction and infusion set/site failures were the most common events reported, occurring in 27 (54.0%) and 18 (36.0%) AEs, respectively. A user- or education-related issue was implicated in 22 (44.0%) events. Pump replacement occurred in 19 of 50 occurrences (38.0%). Additionally, 16 (32.0%) reported a hospital admission or emergency department attendance as a consequence. When compared with those on CSII not reporting an AE, AEs were associated with age <10 years (odds ratio=3.2 [95% confidence interval, 1.7-6.1]) but not with gender, glycosylated hemoglobin, diabetes duration, or pumping duration., Conclusions: This is the first prospective study to look at AEs in modern-generation insulin pumps. AEs appear common and should be anticipated. Their origin is multifactorial, with the pump, associated consumables, and the user all being important factors. Ongoing support and anticipatory education are essential to minimize pump-associated AEs and their impact.

Background: Insulin pumps (for continuous subcutaneous insulin infusion [CSII]) are used widely in type 1 diabetes mellitus. Although there has been considerable study of outcomes, there are few recent data on CSII-associated adverse events and no data on family perceptions of adverse events and their confidence in dealing with them., Subjects and Methods: We approached all families of children and adolescents ≤ 19 years of age on CSII attending the diabetes clinic over a 16-week clinic cycle. Participants completed a retrospective questionnaire examining issues over the previous 12 months. Data on pump adverse events as well as answers to questions pertaining to education and confidence were collected., Results: Our survey received a response rate of 99%, with 235 of the 238 families approached participating. In the preceding 12 months, 104 of 230 (45%) had reported at least one pump-related adverse event (either mechanical or set-related), with an associated 52 of 229 (23%) resulting in pump replacement. This equated to a minimum incidence density of 53 adverse events/100 person-years. Additionally, 18 of 230 (8%) reported a hospital admission or emergency department attendance as a consequence. Pump malfunction and infusion set/site failures were the most common events reported, with one or more events in 58 of 104 (56%) and 47 of 104 (45%), respectively. Adverse events, excluding set/site failures, were associated with older age (13.1 ± 3.4 years vs. 11.9 ± 4 years; P = 0.02)., Conclusions: This is the first study to look at family perceptions of adverse events while using modern CSII. It highlights a high self-reported rate of CSII-related adverse events, pump replacement, and subsequent presentation to the hospital. Potential areas for additional targeted education are identified. Further prospective study examining pump adverse event characteristics and incidence is warranted.

Doctors sometimes struggle with ethically challenging requests for treatment from children's parents. For instance, we have recently had two requests by parents of children, a girl and a boy, each with a severe developmental disability, for hormonal therapy to suppress growth and puberty: the girl's parents requested, in addition, hysterectomy and mastectomy. We propose a reliable approach to assessing the ethical and legal aspects of these and other requests for 'non-therapeutic' treatment of a minor who lacks the capacity to give informed consent. We argue that a doctor should first assess whether the request is one that he or she can, in conscience, accede to, and then, if it is, seek the authorisation of a court. We outline considerations relevant to the doctor's assessment of both the ethical issues and to the need for court authorisation., (© 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Background: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development., Results: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements., Conclusions: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution.

Objective: Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes., Research Design and Methods: We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12-20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol., Results: In this study, 137 patients (18.8%) had diabetic retinopathy signs; of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023-1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02-7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21-1.56]). This association remained after additional adjustment for retinal vascular caliber., Conclusions: Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.

This study, involving 19 centres, establishes the status of medical student radiology teaching in Australia and New Zealand. It aims to document the academic and clinical staff profile involved in teaching, to indicate the methods of instructions used, to outline the available radiology library resources for medical students, to list the textbooks used in teaching and to uncover how many radiology departments are involving medical students in research. The findings can be used to plan and execute further actions that will enhance radiology teaching of medical students.

Background: In the non-diabetic population, intramyocellular lipid (IMCL) accumulation is associated with obesity and poor muscle oxygen supply. IMCL levels are increased in type 1 diabetes, but their significance is less clear., Methods: We studied a group of 16 prepubertal boys (age 6.4-9.9 yr) with type 1 diabetes and a range of glycemic control [hemoglobin A1c (HbA1c) 6.4-10.2%]. Children's adiposity was assessed by anthropometry, muscle oxygen supply by near-infrared spectroscopy (NIRS), abdominal and IMCL content by magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS)., Results: IMCL content did not associate with muscle reoxygenation rate, abdominal adiposity, duration of diabetes, or recent glycemic control. Muscle reoxygenation rate correlated with percentage body fatness (r2 = 0.46, p = 0.004), visceral (r2 = 0.45, p = 0.007) and abdominal subcutaneous fat volume (r2 = 0.63, p = 0.0004), and dietary fat intake (r2 = 0.27, p = 0.03) but not with the duration of diabetes nor HbA1c. HbA1c was significantly related to dietary fat intake only (r2 = 0.28, p = 0.03)., Conclusion: While causality cannot be inferred, interventions aimed at improving muscle oxygen supply, or preventing its deterioration, might reduce the development of adiposity in children with type 1 diabetes.

This study examined the incidence of high peak plantar pressure and plantar callus in 211 adolescents with diabetes mellitus and 57 nondiabetic controls. The percentage of subjects with these anomalies was the same in both groups. Although diabetic subjects were no more likely than nondiabetic controls to have high peak plantar pressure and callus, these anomalies place individuals with diabetes at greater risk of future foot problems. The effects of orthoses, cushioning, and both in combination were monitored in 17 diabetic subjects with high peak plantar pressure and in 17 diabetic subjects with plantar callus; reductions of up to 63% were achieved. Twelve-month follow-up of diabetic subjects fitted with orthoses showed a significant reduction in peak plantar pressure even when the orthoses were removed. The diabetic subjects who had not received any interventions during the same 12-month period showed no significant change in peak plantar pressure.

Objective: This study was designed to explore the timeline of protection against complications in prepubertal children with diabetes, in particular the effects of diabetes duration before age 5 years., Research Design and Methods: In this study, 193 adolescents with prepubertal diabetes onset were followed longitudinally for retinopathy (early background and clinical) and microalbuminuria (albumin excretion rate >7.5 micro g/min and >20 micro g/min). Multiple logistic regression analysis was used to compare the effect of pre- and postpubertal diabetes duration on the risk of each complication in 90 subjects reassessed as young adults. For the entire cohort, Kaplan-Meier estimates were used to determine time free of each complication, and survival was compared in those diagnosed before and after age 5 years. Accelerated failure time modeling was used to estimate the effect of covariates, including diabetes duration before puberty, on the risk of complications., Results: Prepubertal duration improved the prediction for retinopathy over postpubertal duration alone in the young adults. The survival-free period of retinopathy and microalbuminuria was significantly longer (2-4 years) for those diagnosed before age 5 years compared with those diagnosed after age 5 years. Time to onset of all complications increased progressively with longer diabetes duration before gonadarche. Higher HbA(1c) during adolescence had an independent effect on the risk of retinopathy and microalbuminuria., Conclusions: Prepubertal diabetes duration remains a significant predictor of retinopathy in young adults. The effect of time on the risk of retinopathy and microalbuminuria is nonuniform, with an increasing delay in the onset of complications in those with longer prepubertal duration. These findings are of major clinical importance when setting targets of glycemic control in young children who are at greatest risk of hypoglycemia.

A pilot study of the effectiveness of prehospital triage of trauma patients was carried out in a western Sydney between February and July 1988. Triage guidelines were developed to identify seriously injured persons at the incident site who might warrant admission to a Level 3 Trauma Service Hospital (Trauma Centre), as part of the NSW Department of Health trauma services plan. The study results were based on 64% of ambulance trauma transports for which a triage decision was provided. Of trauma transports studied, 3.7% had injuries serious enough to warrant admission to Level 3 Trauma Service Hospital. Ambulance officers correctly triaged 77% of these cases in the field. However, 62% of trauma transports triaged 'severe' or 'critical' did not have injuries serious enough to warrant admission to a Level 3 Trauma Service Hospital. Nevertheless, the triage guidelines compared favourably with similar instruments used elsewhere. Based on the performance of the triage guidelines it was concluded that the introduction of a regionalized trauma service in metropolitan NSW with local bypass is possible.