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BackgroundWe conducted a survey to identify what types of health research could be exempted from research ethics reviews in Australia.MethodsWe surveyed active Australian health researchers and members of Human Research Ethics Committees (HREC). We presented the respondents with eight hypothetical research scenarios, involving: N of 1 trials, no treatment studies, linked data sets, surplus samples, audits, surveys, interviews with patients, and professional opinion. We asked whether these scenarios should or should not be exempt from ethics review, and to provide (optional) explanations. We analysed the reasons thematically, to identify Top 3 reasons underlying the decisions.ResultsMost frequent reasons for requiring ethics reviews, included: the need for independent oversight, privacy/confidentiality issues, review of scientific rigour, and publishing considerations. Most frequent reasons for exempting scenarios from reviews, included: level of risk, study design, privacy/confidentiality issues, and standard clinical practice. Four research scenarios listed the same Top 3 reasons for requiring ethics reviews: need for independent oversight, review of scientific rigour, privacy/confidentiality. Reasons for exempting were less uniform, but low risk was a Top 3 reason for 7 scenarios, and study design for 4 scenarios. Privacy/confidentiality was given as a Top 3 reason for both requiring and exempting from ethics the same two scenarios.ConclusionsThe most frequently offered reasons in support of requiring ethics reviews for research scenarios are more uniform than those for exempting them. However, considerable disagreement exists about when the risks of research are so minimal that the exemption is appropriate.

Objectives: To determine age group‐ and cause‐of‐death‐specific contributions to area socioeconomic status (SES), sex and remoteness life expectancy inequalities. Methods: Mortality and estimated residential population data from New South Wales, Australia, over 2010–2012 was used to calculate life expectancy. Inequalities by sociodemographic groups were partitioned into age group‐ and cause‐of‐death‐specific contributions. Results: The largest contributions to SES differentials in life expectancy were observed at 60–84 years of age; for cancer, cardiovascular, endocrine and respiratory causes of death; and additionally external causes of death for males. Sex inequalities ranged from 3.6 to 5.2 years, with common causes of death such as cardiovascular disease and cancer in late adulthood (60+ years) accounting for the bulk of the differences. Smaller differences in life expectancy were observed by remoteness, with the largest contributions observed in ages 85 years and above, and for cardiovascular, mental, cancer and external causes of death. Conclusions: Common causes of death in late adulthood accounted for the bulk of life expectancy inequalities. Implications for public health: Development of policy and interventions aimed at addressing social determinants, such as proposed by the WHO's Global Plan of Action, are needed to help reduce sociodemographic inequalities in lifespan.

Category: Diabetes Introduction/Purpose: Diabetic ulcers carry with it extensive morbidity. The microbiome of diabetic foot infections have previously been shown to be polymicrobial. We hypothesized that ulcer treatment would normalize the foot microbiome. Methods: Microbiome profiles of the fore, mid and hind diabetic foot. Diabetic foot (with ulcer) were taken pre and post treatment with a combination of surgical debridement, local and systemic antibiotics. 10 subjects were studied. Microbiome graphs and images pre and post treatment of feet are shown. Results: The microbiome profile of the diabetic foot almost completely normalized to that of normal flora. Before treatment, the foot microbiome was associated with polymicrobial pathogenic bacteria mostly away from the ulcer. The ulcer itself only contained minimal species, albeit pathogenic bacteria. The differences in profiles between the pre and post treatment were significantly different p < 0.01. Conclusion: Chicken or egg, the foot microbiome almost completely reverts to normal flora with simple ulcer debridement and local/systemic antibiotics. Our data point possibly suggest ulcers could be prevented by reducing pathogenic microbiome load (chlorhexidine washes) or microbiome transplants. We next move to controls as a proof of concept.

This article describes the evaluation of enhanced surveillance that was conducted on an older age-group of children with pertussis (ages 5-9 years), in addition to the routine follow-up of a younger age-group (ages 0-4 years) in Sydney Local Health District during 2015. We found little incremental benefit in this policy in terms of identifying additional high-risk contacts, despite a greatly increased workload.

ObjectivesLevel of education and genetic risk are key predictors of cardiovascular disease (CVD). While several studies have explored the causal mechanisms of education effects, it remains uncertain to what extent genetic risk is mediated by established CVD risk factors. This study sought to investigate this and explored the mediation of education and genetic effects on CVD by established cardiovascular risk factors in the Framingham Heart Study (FHS).DesignProspective observational cohort study.Participants7017 participants from the FHS.SettingCommunity-based cohort of adults in Framingham, Massachusetts, USA.Primary outcome measureIncident CVD. The total effects of education and genetic predisposition using a 63-variant genetic risk score (GRS) on CVD, as well as those mediated by established CVD risk factors, were assessed via mediation analysis based on the counterfactual framework using Cox proportional hazards regression models.ResultsOver a median follow-up time of 12.0 years, 1091 participants experienced a CVD event. Education and GRS displayed significant associations with CVD after adjustment for age and sex and the established risk factors smoking, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), body mass index, systolic blood pressure (SBP) and diabetes. For education effects, smoking, HDL-C and SBP were estimated to mediate 18.8% (95% CI 9.5% to 43%), 11.5% (95% CI 5.7% to 29.0%) and 4.5% (95% CI 1.6% to 13.3%) of the total effect of graduate degree, respectively, with the collective of all risk factors combined mediating 38.5% (95% 24.1% to 64.9%). A much smaller proportion of the effects of GRS were mediated by established risk factors combined (17.6%, 95% CI 2.4% to 35.7%), with HDL-C and TC mediating 11.5% (95% CI 6.2% to 21.5%) and 3.1% (95% CI 0.2% to 8.3%), respectively.ConclusionsUnlike education inequalities, established risk factors mediated only a fraction of GRS effects on CVD. Further research is required to elucidate the underlying causal mechanisms of genetic contributions to CVD.

Objectives To assess the association between ED occupancy and relevant outcomes including ED waiting times, rates of admission and representation and length of stay when hospitalised. Methods Retrospective study of all ED presentations by New South Wales (NSW), Australia, residents to 15 NSW public, principal referral or paediatric specialist hospitals between 1 January to 31 December 2015 (N = 935 282). ED data were linked longitudinally (to ED data) and cross-sectionally to hospital admissions data. An ED-system measure of occupancy was assigned to each ED record. The study outcomes were ED waiting time, admission to hospital, 28 day representation, and length of stay (LOS) when admitted. Outcomes were analysed using univariate analyses and multivariable general linear and binary logistic regression models. Results Increased ED occupancy was associated with increased ED waiting times, particularly at low-baseline occupancy (e.g. rate ratio = 2.22, 95% confidence interval [CI] [2.10-2.35], for non-urgent triaged patients). However, results were conditional on triage category, such that estimated effects were smaller or not significant in emergency and resuscitation triaged patients (e.g. rate ratio = 1.59, 95% CI [1.52-1.65], for emergency patients). ED occupancy only showed small or no associations with admission to hospital, 28 day representation and LOS when admitted. Conclusions Higher ED occupancy was associated with increased waiting times conditional on triage category and baseline occupancy. Collectively, the results show that NSW principal referral EDs are robust, and are currently capable of handling variation in occupancy by prioritising treatment for the most urgent patients.

Introduction Currently there are no clinical screening tests available to identify pregnancies at risk of developing preeclampsia (PET) and/or intrauterine growth restriction (IUGR), both of which are associated with abnormal placentation. Metabolic profiling is now a stable analytical platform used in many laboratories and has successfully been used to identify biomarkers associated with various pathological states. Methods We used nuclear magnetic resonance spectroscopy (NMR) to metabolically profile serum samples collected from 143 pregnant women at 26–41 weeks gestation with pregnancy outcomes of PET, IUGR, PET IUGR or small for gestational age (SGA) that were age-matched to normal pre/term pregnancies. Results Spectral analysis found no difference in the measured metabolites from normal term, pre-term and SGA samples, and of 25 identified metabolites, only glutamate was marginally different between groups. Of the identified metabolites, 3-methylhistidine, creatinine, acetyl groups and acetate, were determined to be independent predictors of PET and produced area under the curves (AUC) = 0.938 and 0.936 for the discovery and validation sets. Only 3-hydroxybutyrate was determined to be an independent predictor of IUGR, however the model had low predictive power (AUC = 0.623 and 0.581 for the discovery and validation sets). Conclusions A sub-panel of metabolites had strong predictive power for identifying PET samples in a validation dataset, however prediction of IUGR was more difficult using the identified metabolites. NMR based metabolomics can identify metabolites strongly associated with disease and has the potential to be useful in developing early clinical screening tests for at risk pregnancies.

Background To investigate whether the adverse infant health outcomes associated with early birth and severe neonatal morbidity (SNM) persist beyond the first year of life and impact on paediatric hospitalisations for children up to 6 years of age. Methods The study population included all singleton live births, >32 weeks gestation in New South Wales, Australia, in 2001–2005, with follow-up to 6 years of age. Birth data were probabilistically linked to hospitalisation data (n = 392 964). The odds of hospitalisation, mean hospital length of stay (LOS) and costs, and cumulative LOS were evaluated by gestational age and SNM using multivariable analyses. Results A total of 74 341 (18.9%) and 41 404 (10.5%) infants were hospitalised once and more than once, respectively. SNM was associated with increased odds of hospitalisation once (adjusted odds ratio [aOR] 1.16 [95% confidence interval 1.10, 1.22]) and more than once [aOR 1.51 (1.43, 1.61)]. Decreasing gestational age was associated with increasing odds of hospitalisation more than once from aOR 1.19 at 37–38 weeks to 1.49 at 33–34 weeks. Average LOS and costs per hospital admission were increased with SNM but not with decreasing gestational age. Cumulative LOS was significantly increased with SNM and decreasing gestational age. Conclusions Adverse effects of SNM and early birth persist between 1 and 6 years of age. Strategies to prevent early birth and reduce SNM, and to increase health monitoring of vulnerable infants throughout childhood may help reduce paediatric hospitalisations.

Summary We determined brain to liver weight ratio (BLWR) thresholds for fetal growth restriction (FGR) using autopsy information on 395 perinatal deaths comprising stillborn babies who died during labour and neonatal deaths. FGR was defined using two methods: (1) birth weight for gestational age (WGA) less than the 10th percentile; and (2) WGA less than the 10th percentile or discordant birth weight/length. The association between BLWR and FGR was investigated using odds ratios, and classification statistics were calculated for a range of BLWR thresholds. Using WGA, 84 cases (21.3%) were FGR and a further 15 cases (n = 99, 25%) had discordant birth weight/length. The BLWR ranged from 1.02 to 7.30 and was positively associated with FGR. BLWR was not associated with FGR for babies with congenital central nervous system or chromosomal abnormalities. Excluding these, for FGR defined using WGA and discordant birth weight/length, a BLWR threshold of 5.0 was 100% predictive of FGR. A BLWR threshold of 3.0 for babies over 28 weeks gestation and 3.7 for more preterm babies optimised case detection while minimising missed and false positive cases. Additional evidence of FGR should be sought for babies with a BLWR of less than 5.0 to confirm FGR.

Objectives Despite being one of the healthiest countries in the world, Australia displays substantial mortality differentials by socioeconomic disadvantage, remoteness and sex. In this study, we examined how these mortality differentials translated to differences in life expectancy between 2001 and 2012. Design and setting Population-based study using mortality and estimated residential population data from Australia9s largest state, New South Wales (NSW), between 2001 and 2012. Age-group-specific death rates by socioeconomic disadvantage quintile, remoteness (major cities vs regional and remote areas), sex and year were estimated via Poisson regression, and inputted into life table calculations to estimate life expectancy. Results Life expectancy decreased with increasing socioeconomic disadvantage in males and females. The disparity between the most and least socioeconomically deprived quintiles was 3.77 years in males and 2.39 years in females in 2012. Differences in life expectancy by socioeconomic disadvantage were mostly stable over time. Gender gaps in life expectancy ranged from 3.50 to 4.93 years (in 2012), increased with increasing socioeconomic disadvantage and decreased by ∼1 year for all quintiles between 2001 and 2012. Overall, life expectancy varied little by remoteness, but was 1.8 years higher in major cities compared to regional/remote areas in the most socioeconomically deprived regions in 2012. Conclusions Socioeconomic disadvantage and sex were strongly associated with life expectancy. The disparity in life expectancy across the socioeconomic spectrum was larger in males and was stable over time. In contrast, gender gaps reduced for all quintiles between 2001 and 2012, and a remoteness effect was evident in 2012, but only for those living in the most deprived areas.

Research capacity building in healthcare works to generate and apply new knowledge to improve health outcomes; it creates new career pathways, improves staff satisfaction, retention and organisational performance. While there are examples of investment and research activity in rural Australia, overall, rural research remains under-reported, undervalued and under-represented in the evidence base. This is particularly so in primary care settings. This lack of contextual knowledge generation and translation perpetuates rural–metropolitan health outcome disparities. Through greater attention to and investment in building research capacity and capability in our regional, rural and remote health services, these issues may be partially addressed. It is proposed that it is time for Australia to systematically invest in rurally focussed, sustainable, embedded research capacity building.

Background Although infant and child mortality rates have decreased substantially worldwide over the past two decades, efforts continue in many nations to further these declines. The identification of pertinent perinatal factors that are associated with early childhood mortality would help with these efforts. We investigated the association of two crucial perinatal factors, gestational age and severe neonatal morbidity at birth, with mortality during infancy (29-364 days) and early childhood (1-5 years). Methods The study population included all singleton livebirths, ≥32 weeks' gestation in New South Wales, Australia in 2001-11. Birth data were linked to hospitalisation morbidity data and deaths data (linked birth cohort n = 871 916), and multivariable Cox regression models were used to assess mortality. Results The median follow-up time per child was 4.95 years (range 0.00-5.92 years; 3 614 738 total person-years), with 984 deaths observed. Gestational age was associated with increased mortality, and specifically from deaths attributable to infections, respiratory conditions, and injuries during infancy, but not during early childhood. Severe neonatal morbidity strongly mediated the effects of gestational age during infancy, but not during early childhood, and was associated with increased mortality from circulatory, nervous, and respiratory system causes. Conclusions The direct effects of gestational age on mortality extended up to 1 year of age, whereas severe neonatal morbidity remained associated with heightened mortality into early childhood. Efforts to maximise the health and well-being of vulnerable infants, with emphasis on preventing infections and injuries, may help further reduce early childhood mortality.

Objective To explore the patterns of low acuity patient (LAP) presentations to EDs in New South Wales (NSW), Australia. Methods Retrospective study of NSW public hospital ED presentations between January 2013 and December 2014 that were registered in the NSW Emergency Department Data Collection (n = 409 035). LAPs were defined according to the Australian Institute of Health and Welfare (AIHW), Sprivulis and multiple ACEM methods. Multivariable logistic regression was used to assess the adjusted odds of LAP ED presentation by a suite of sociodemographic factors. Results The percentage of LAPs varied considerably by definition, being as high as 54.7% (inner regional areas) and as low as 3.2% (major cities) using revised ACEM methods modified to contain unlimited consultation times or consultation times of 15 min or less, respectively. For each method, higher proportions of LAPs were observed in inner regional and remote/very remote areas relative to major cities. LAP ED presentations, based on ACEM definition with 1 h or 15 min consultation times, were greater in younger patients, increased during out of business hours and weekends, and decreased with increasing general practitioner (GP) density. Conclusion The percentage of LAPs varied substantially by definition, and further work is required to validate the methods, particularly around the appropriateness of length of consultation time with ACEM, between different hospitals and remoteness areas. Age was strongly associated with low acuity, with substantial effects also observed for GP density, and attendances during out of hours and weekends.

Objectives To investigate survival, hospitalization, and acute-care costs of very (28-31 weeks' gestation) and moderate preterm (32-33 weeks' gestation) infants in the first 6 years of life and compare outcomes with the more widely studied extremely preterm infants (24-27 weeks' gestation) and to full term (low risk) infants (39-40 weeks' gestation). Study design Birth data from all women residing in New South Wales, Australia, with gestational ages between 24-33 and 39-40 weeks in 2001-2011 were linked probabilistically to hospitalization and mortality data. Study outcomes were evaluated with the use of descriptive and multivariable analyses at birth (N = 559 532), discharge (N = 540 240), and at 1 (N = 487 447) and 6 years of age (N = 230 498). Results Mortality was greatest among extremely preterm infants (eg, 31.2% within 6 years) and decreased with increasing gestational age. Likewise, hospitalization within the first year of life increased with decreasing gestational age (aOR 5.5 [95% CI 4.7-6.4], 3.7 [3.4-4.0], and 2.6 [2.5-2.8] for birth at 24-27, 28-31, and 32-33 weeks' gestation, relative to 39-40 weeks' gestation). Hospitalization remained significantly increased with preterm birth at each year of age up to 6 years (aORs 1.3-1.6 at 6 years). Cumulative costs were significantly greater with preterm birth within the first year of life, and also between 1 and 6 years of age. Conclusions The risks of adverse health outcomes were significantly greater in very and moderately preterm infants relative to full term infants but lower than extremely preterm infants. Crucially, preterm birth was associated with prolonged increased odds of hospitalization (up to age 6 years), contributing to greater resource use.

Population ageing presents significant challenges for many developed nations. Accurately forecasting the likely future burden of age-related medical conditions, such as hip fracture, is critical. In this study, we present estimates of the current and future burden of hip fracture in NSW, Australia, providing crucial information for future health care planning. The aims of this study were to investigate the burden of hip fracture in Australia’s largest state, New South Wales (NSW), and to build a prediction model to forecast the likely future burden of hip fracture from 2016 to 2036 in persons aged 50 years or more. A retrospective population-based cohort study was conducted using NSW hospitalisation data. Standardised incident hip fracture rates and hip fracture-related acute care length of stay and costs were estimated. Predictive negative binomial regression modelling using age, gender and local health district and year covariates together with projected NSW populations was applied to forecast future hip fractures. Total incident hip fractures increased 8.8 % over a 12-year period from 2000/2001 to 2011/2012 despite declining age-standardised rates. Estimates of acute care length of stay for the treatment of hip fracture ranged from 10 to 15 days and acute care costs ranged between 21 and 29,000 Australian dollars per fracture. By 2036, incident hip fractures are projected to rise by 35.2 %, assuming a continued decline in the rate of hip fracture or by 107.5 % if the current decline in the rate does not continue. Acute care length of stay and costs are each predicted to rise between 37.1 and 110.4 % by 2036. An ageing population and changing demographics will continue to drive the increasing burden of incident hip fractures in NSW and Australia in the foreseeable future. These anticipated changes provide important information for the planning and management of future hip fracture care.

Loading of the rat ulna is an ideal model to examine stress fracture healing. The aim of this study was to undertake a detailed examination of the histology, histomorphometry and gene expression of the healing and remodelling process initiated by fatigue loading of the rat ulna. Ulnae were harvested 1, 2, 4, 6, 8, and 10 weeks following creation of a stress fracture. Stress fracture healing involved direct remodelling that progressed along the fracture line as well as woven bone proliferation at the site of the fracture. Histomorphometry demonstrated rapid progression of basic multicellular units from 1 to 4 weeks with significant slowing down of healing by 10 weeks after loading. Quantitative PCR was performed at 4 hours, 24 hours, 4 days, 7 days, and 14 days after loading. Gene expression was compared to an unloaded control group. At 4 hours after fracture, there was a marked 220-fold increase (P

Objective To determine a practical approach for deriving life expectancy estimates in Australian New South Wales local government areas which display a large diversity in population sizes. Design Population-based study utilising mortality and estimated residential population data. Setting 153 local government areas in New South Wales, Australia. Outcome measures Key performance measures of Chiang II, Silcocks, adjusted Chiang II and Bayesian random effects model methodologies of life expectancy estimation including agreement analysis of life expectancy estimates and comparison of estimate SEs. Results Chiang II and Silcocks methods produced almost identical life expectancy estimates across a large range of population sizes but calculation failures and excessively large SEs limited their use in small populations. A population of 25 000 or greater was required to estimate life expectancy with SE of 1 year or less using adjusted Chiang II (a composite of Chiang II and Silcocks methods). Data aggregation offered some remedy for extending the use of adjusted Chiang II in small populations but reduced estimate currency. A recently developed Bayesian random effects model utilising the correlation in mortality rates between genders, age groups and geographical areas markedly improved the precision of life expectancy estimates in small populations. Conclusions We propose a hybrid approach for the calculation of life expectancy using the Bayesian random effects model in populations of 25 000 or lower permitting the precise derivation of life expectancy in small populations. In populations above 25 000, we propose the use of adjusted Chiang II to guard against violations of spatial correlation, to benefit from a widely accepted method that is simpler to communicate to local health authorities and where its slight inferior performance compared with the Bayesian approach is of minor practical significance.