Professor Liz Holliday

Introduction: An aging population and advances in surgery have led to increasing need for geriatric management of elderly patients undergoing emergency general surgical care. Integration of a proactive geriatric service for these patients may beneficially impact both traditionally measured hospital and patient-based metrics. Here, we synthesize evidence regarding measurable outcomes of embedded geriatric care within emergency general surgery. Methods: A comprehensive search was conducted across Medline, Embase, Cochrane Library, CINAHL, and Scopus databases by two independent reviewers. The included publications reported outcomes of embedded geriatric services in emergency general surgery. Prespecified outcomes assessed in these studies included patient-reported outcomes, length of stay (LOS), mortality rate, complication rate, intensive care admission, readmission rate, and institutionalization. Results: A total 3100 studies were imported, and eight prospective prepost studies were included in the final review. Length of stay, mortality rate, and medical complication rates were the most frequently assessed outcomes, with each recorded in at least 5 of the 8 included studies. 7 of the 8 studies reported reduced LOS, with four of these reporting a statistically significant difference. The results were variable for other hospital outcomes, including mortality, readmission, and complication rates. Only one source reported on patient-related outcomes, utilizing two tools at multiple time points. No significant prepost effects on patient-related outcomes were noted in this study. Conclusions: Published data on integrating geriatric care in emergency general surgery is limited, but decreased LOS is consistently reported. Further research is necessary to confirm wider effects of integrated geriatric care on relevant hospital and patient outcomes.

Background: Remunerated telehealth consultations were introduced in Australia in 2020 in response to the COVID-19 pandemic. Videoconferencing has advantages over telephone-consulting, including improved diagnostic and decision-making accuracy. However, videoconferencing uptake in Australia has been low. This study aimed to establish prevalence and associations of video versus telephone consultations in Australian general practice (GP) registrars' practice. Methods: A cross-sectional analysis of data from 2020 to 2021 (three 6-monthly data-collection rounds) from the Registrars Clinical Encounters in Training (ReCEnT) study. GP registrars record details of 60 consecutive consultations every 6-month term, for a total of 3 terms. Univariable and multivariable logistic regression were performed within the Generalized Estimating Equations framework with the outcome video versus telephone. Results: 102,286 consultations were recorded by 1,168 registrars, with 21.4% of consultations performed via telehealth. Of these, telephone accounted for 96.6% (95% CI: 96.3-96.8%) and videoconferencing for 3.4% (95% CI: 3.2-3.7%). Statistically significant associations of using videoconferencing, compared to telephone, included longer consultation duration (OR 1.02, 95% CI: 1.01-1.03 per minute; and mean 14.9 versus 12.8 min), patients aged 0-14 years old (OR 1.29, 95% CI: 1.03-1.62, compared to age 15-34), patients new to the registrar (OR 1.19, 95% CI: 1.04-1.35), part-time registrars (OR 1.84, 95% CI: 1.08-3.15), and areas of less socioeconomic disadvantage (OR 1.27, 95% CI: 1.00-1.62 per decile). Conclusions: Registrars' telehealth consultations were mostly performed via telephone. Telephone use being associated with socioeconomic disadvantage has health equity implications. Future research should explore barriers to videoconferencing use and strategies to increase its uptake.

Introduction: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP. Methods: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years. Results: Our analyses prioritized myofibroblasts and endothelial cells, among the total of 33 annotated cell type, as specifically involved in BP regulation (P < 0.05/33, i.e., 0.001515). Enrichment of heritability for systolic BP (SBP) was observed in myofibroblast cells in mature human kidney cortex, and enrichment of heritability for diastolic BP (DBP) was observed in descending vasa recta and peritubular capillary endothelial cells as well as stromal myofibroblast cells. The new finding of myofibroblast, the significant cell type for both BP traits, was consistent in 8 replication efforts using 7 sets of independent data, including in human fetal kidney, in East-Asian (EAS) ancestry, using mouse single-cell RNA sequencing (scRNA-seq) data, and when using another prioritization method. Conclusion: Our findings provide a solid basis for follow-up studies to further identify genes and mechanisms in myofibroblast cells that underlie the regulation of BP.

Background: Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety; however, few studies jointly examine these risk factors. This study aimed to prospectively examine the joint association of physical activity (PA) and insomnia symptoms with onset of poor mental health in adults. Methods: Participants from the 2013 to 2018 annual waves of the Household Income and Labour Dynamics in Australia panel study who had good mental health (Mental Health Inventory-5 >54) in 2013, and who completed at least 1 follow-up survey (2014¿2018), were included (n = 10,977). Poor mental health (Mental Health Inventory-5 = 54) was assessed annually. Baseline (2013) PA was classified as high/moderate/low, and insomnia symptoms (i.e., trouble sleeping) were classified as no insomnia symptoms/insomnia symptoms, with 6 mutually exclusive PA-insomnia symptom groups derived. Associations of PA¿insomnia symptom groups with onset of poor mental health were examined using discrete-time proportional-hazards logit-hazard models. Results: There were 2322 new cases of poor mental health (21.2%). Relative to the high PA/no insomnia symptoms group, there were higher odds (odds ratio and 95% confidence interval (95%CI)) of poor mental health among the high PA/insomnia symptoms (OR = 1.87, 95%CI: 1.57¿2.23), moderate PA/insomnia symptoms (OR = 1.93, 95%CI: 1.61¿2.31), low PA/insomnia symptoms (OR = 2.33, 95%CI: 1.96¿2.78), and low PA/no insomnia symptoms (OR = 1.14, 95%CI: 1.01¿1.29) groups. Any level of PA combined with insomnia symptoms was associated with increased odds of poor mental health, with the odds increasing as PA decreased. Conclusion: These findings highlight the potential benefit of interventions targeting both PA and insomnia symptoms for promoting mental health.

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12¿16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

Background: Little is known about the physical and mental health impact of exposure to landscape fire smoke in women with asthma. This study examined the health impacts and information-seeking behaviours of women with asthma exposed to the 2019/2020 Australian fires, including women who were pregnant. Methods: Women with asthma were recruited from the Breathing for Life Trial in Australia. Following the landscape fire exposure period, self-reported data were collected regarding symptoms (respiratory and non-respiratory), asthma exacerbations, wellbeing, quality of life, information seeking, and landscape fire smoke exposure mitigation strategies. Participants' primary residential location and fixed site monitoring was used to geolocate and estimate exposure to landscape fire-related fine Particulate Matter (PM2.5). Results: The survey was completed by 81 pregnant, 70 breastfeeding and 232 non-pregnant and non-breastfeeding women with asthma. Participants had a median daily average of 17 µg/m3 PM2.5 and 105 µg/m3 peak PM2.5 exposure over the fire period (October 2019 to February 2020). Over 80% of participants reported non-respiratory and respiratory symptoms during the fire period and 41% reported persistent symptoms. Over 82% reported asthma symptoms and exacerbations of asthma during the fire period. Half the participants sought advice from a health professional for their symptoms. Most (97%) kept windows/doors shut when inside and 94% stayed indoors to minimise exposure to landscape fire smoke. Over two in five (43%) participants reported that their capacity to participate in usual activities was reduced due to prolonged smoke exposure during the fire period. Participants reported greater anxiety during the fire period than after the fire period (mean (SD) = 53(13) versus 39 (13); p < 0.001). Two in five (38%) pregnant participants reported having concerns about the effect of fire events on their pregnancy. Conclusion: Prolonged landscape fire smoke exposure during the 2019/2020 Australian fire period had a significant impact on the health and wellbeing of women with asthma, including pregnant women with asthma. This was despite most women taking actions to minimise exposure to landscape fire smoke. Effective and consistent public health messaging is needed during landscape fire events to guard the health of women with asthma.

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2¿h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke.

Background Individualised music listening has been shown to reduce agitation and improve mood in people with dementia. However, there is a paucity of research describing the cost of implementing such interventions in residential care settings for older people. Aim To determine the cost of implementing an individualised music intervention for older people with dementia in residential aged care in Australia. Method A simple cost analysis was undertaken to determine the cost of delivering the individualised music intervention to 32 older people with dementia at two residential aged care facilities in New South Wales. The analysis took into consideration the operating, training and delivery costs, as well as the costs of purchasing the music equipment and downloads. Results The cost of delivering the individualised music intervention was found to be AU$6,623.76 per year ¿ or AU$3.98 per resident per week, at 2017 values. At 2022 values, this equates to an annual cost of AU$7,130.07 (£4,031.85) for 32 residents and a weekly cost of AU$4.28 (£2.42) per resident per week. Conclusion The cost of implementing the individualised music intervention was relatively low compared with the overall cost of residential aged care for older people with dementia.

Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85¿×¿10-9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n¿=¿27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.

Introduction: Continuous surveillance of stroke admissions has been conducted in the Hunter region, Australia, over the past two decades. We aimed to describe the trends in incidence rates of hospitalised stroke and case-fatality rates in this region, 2001-2019. Methods: From a hospital-based stroke registry, data for admitted adult stroke patients residing in the Hunter region were collected using ICD-10 codes for ischemic and haemorrhagic stroke. Negative binomial regression and logistic regression analysis were used to analyse trends for age-standardised and age-specific incidence rates of hospitalised stroke and 28-day case-fatality rates. Results: A total of 14,662 hospitalisations for stroke in 13,242 individuals were registered. The age-standardised incidence rate declined from 123 per 100,000 population in the 2001-2005 epoch to 96 in the 2016-2019 epoch (mean annual change -2.0%, incidence rate ratio (IRR) = 0.980 [95%CI: 0.976-0.984]). Age-specific analyses identified significant reduction in the group aged 75-84 (1039 per 100,000 population in 2001-2005 to 633 in 2016-2019, annual change -3.5%, IRR= 0.965 [95%CI: 0.960-0.970]). The 28-day case-fatality rates fluctuated over time (18.5% in 2001-2005, 20.8% in 2010-2015, and 17.8% in 2016-2019). Projected population aging suggests annual volume of patients with new stroke will increase by 77% by 2041 if incidence rates remain unchanged at the 2016-2019 level. Conclusion: Although age-standardised hospitalised stroke incidence rates have declined in the Hunter region, the health system will face an increase in stroke hospitalisations related to the aging population.

ABSTRACT: INTRODUCTION: Over-prescription of antibiotics for common infective conditions is an important health issue. Infective conjunctivitis represents one of the most common eye-related complaints in general practice. Despite its self-limiting nature, there is evidence of frequent general practitioner (GP) antibiotic prescribing for this condition, which is inconsistent with evidence-based guidelines. AIM: To investigate the prevalence and associations of GP registrars' (trainees') prescription of antibiotics for infective conjunctivitis. METHODS: We performed a cross-sectional analysis of the Registrar Encounters in Clinical Training (ReCEnT) ongoing prospective cohort study, which documents GP registrars' clinical consultations (involving collection of information from 60 consecutive consultations, at three points during registrar training). The outcome of the analyses was antibiotic prescription for a new diagnosis of conjunctivitis. Patient, registrar, practice and consultation variables were included in uni- and multivariable logistic regression analyses to test associations of these prescriptions. RESULTS: In total, 2333 registrars participated in 18 data collection rounds from 2010 to 2018. There were 1580 new cases of infective conjunctivitis (0.31% of all problems). Antibiotics (mainly topical) were prescribed in 1170 (74%) of these cases. Variables associated with antibiotic prescription included patients' Aboriginal or Torres Strait Islander status, registrar organisation of a follow up (both registrar and other GP follow up), and earlier registrar training term (more junior status). DISCUSSION: GP registrars, like established GPs, prescribe antibiotics for conjunctivitis in excess of guideline recommendations, but prescribing rates are lower in later training. These prescribing patterns have educational, social and economic consequences. Further educational strategies may enhance attenuation of registrars' prescribing during training.

Objective Examine the relationship between preconception stress and offspring birth weight. Setting Population-based cohort study linked with state-based administrative perinatal data. Participants 6100 births from 3622 women from the 1973-1978 cohort of the Australian Longitudinal Study of Women's Health who (1) recorded a singleton birth between January 1997 and December 2011; (2) returned at least one follow-up survey within 3 years of conception; and (3) had complete data on perceived stress prior to conception. Primary outcome measures Linear generalised estimating equations were used to examine the relationship between preconception stress and a continuous measure of birth weight, exploring differences based on birth order and stress chronicity. The minimal sufficient adjustment set of covariates was determined by a directed acyclic graph. Results For all births, there was no relationship between moderate/high acute or chronic stress and offspring birth weight in grams. Among first births only, there was a trend towards a relationship between moderate/high chronic stress and offspring birth weight. Offspring sex was associated with birth weight in all models, with female babies born lighter than male babies on average, after adjusting for covariates (p<0.0001). Conclusions Effects of preconception stress on birth weight was largely driven by time to conception. With the timing of stress critical to its impact on obstetrical outcomes, preconception care should involve not only reproductive life planning but the space to provide interventions at critical periods so that optimal outcomes are achieved.

Objectives: Sedentary behaviour research is a relatively new field, much of which has emerged since the widespread acceptance of clinical trial registration. The aim of this study was to investigate the trial registration and related issues in studies investigating the effect of frequent activity interruptions to prolonged sitting-time. Methods: Secondary analysis of a scoping review including systematic searches of databases and trial registries. We included experimental studies investigating the effects of frequent activity interruptions to prolonged sitting-time. Results: We identified 32 trials published in 45 papers. Only 16 (50%) trials were registered, with all 16 trials being completed and published. Of the unregistered trials, we identified three (19%) for which similarities in the sample size and participant demographics across papers was suggestive of duplicate publication. Identification of potential duplicate publications was difficult for the remaining 13 (81%). Results from 53 (76%) of the 70 registered outcomes were published, but 11 (69%) registered trials reported results from additional outcomes not prospectively registered. A total of 46 different outcomes (out of 53 reported outcome measures, similar measures were collated) were reported across all trials, 31 (67%) of which were collected in =2 trials. Conclusions: We found direct evidence of trial registration issues in experimental trials of breaking up sitting-time. The lack of prospective registration of all trials, and the large number of outcomes measured per trial are key considerations for future research in this field. These issues are unlikely to be confined to the field of sedentary behaviour research.

Background: To examine if a composite activity-sleep behaviour index (ASI) mediates the effects of a combined physical activity and sleep intervention on symptoms of depression, anxiety, or stress, quality of life (QOL), energy and fatigue in adults. Methods: This analysis used data pooled from two studies: Synergy and Refresh. Synergy: Physically inactive adults (18¿65 years) who reported poor sleep quality were recruited for a two-arm Randomised Controlled Trial (RCT) (Physical Activity and Sleep Health (PAS; n = 80), or Wait-list Control (CON; n = 80) groups). Refresh: Physically inactive adults (40¿65 years) who reported poor sleep quality were recruited for a three-arm RCT (PAS (n = 110), Sleep Health-Only (SO; n = 110) or CON (n = 55) groups). The SO group was omitted from this study. The PAS groups received a pedometer, and accessed a smartphone/tablet "app" using behaviour change strategies (e.g., self-monitoring, goal setting, action planning), with additional email/SMS support. The ASI score comprised self-reported moderate-to-vigorous-intensity physical activity, resistance training, sitting time, sleep duration, efficiency, quality and timing. Outcomes were assessed using DASS-21 (depression, anxiety, stress), SF-12 (QOL-physical, QOL-mental) and SF-36 (Energy & Fatigue). Assessments were conducted at baseline, 3 months (primary time-point), and 6 months. Mediation effects were examined using Structural Equation Modelling and the product of coefficients approach (AB), with significance set at 0.05. Results: At 3 months there were no direct intervention effects on mental health, QOL or energy and fatigue (all p > 0.05), and the intervention significantly improved the ASI (all p < 0.05). A more favourable ASI score was associated with improved symptoms of depression, anxiety, stress, QOL-mental and of energy and fatigue (all p < 0.05). The intervention effects on symptoms of depression ([AB; 95%CI] -0.31; - 0.60,-0.11), anxiety (- 0.11; - 0.27,-0.01), stress (- 0.37; - 0.65,-0.174), QOL-mental (0.53; 0.22, 1.01) and ratings of energy and fatigue (0.85; 0.33, 1.63) were mediated by ASI. At 6 months the magnitude of association was larger although the overall pattern of results remained similar. Conclusions: Improvements in the overall physical activity and sleep behaviours of adults partially mediated the intervention effects on mental health and quality of life outcomes. This highlights the potential benefit of improving the overall pattern of physical activity and sleep on these outcomes. Trial registration: Australian New Zealand Clinical Trial Registry: ACTRN12617000680369; ACTRN12617000376347. Universal Trial number: U1111¿1194-2680; U1111¿1186-6588. Human Research Ethics Committee Approval: H-2016-0267; H-2016¿0181.

Background Cardiorespiratory fitness (CRF) is an important marker of current and future health status. The primary aim of our study was to evaluate the impact of a time-efficient school-based intervention on older adolescents' CRF. Methods Two-arm cluster randomised controlled trial conducted in two cohorts (February 2018 to February 2019 and February 2019 to February 2020) in New South Wales, Australia. Participants (N=670, 44.6% women, 16.0±0.43 years) from 20 secondary schools: 10 schools (337 participants) were randomised to the Burn 2 Learn (B2L) intervention and 10 schools (333 participants) to the control. Teachers in schools allocated to the B2L intervention were provided with training, resources, and support to facilitate the delivery of high-intensity interval training (HIIT) activity breaks during curriculum time. Teachers and students in the control group continued their usual practice. The primary outcome was CRF (20 m multi-stage fitness test). Secondary outcomes were muscular fitness, physical activity, hair cortisol concentrations, mental health and cognitive function. Outcomes were assessed at baseline, 6 months (primary end-point) and 12 months. Effects were estimated using mixed models accounting for clustering. Results We observed a group-by-time effect for CRF (difference=4.1 laps, 95% CI 1.8 to 6.4) at the primary end-point (6 months), but not at 12 months. At 6 months, group-by-time effects were found for muscular fitness, steps during school hours and cortisol. Conclusions Implementing HIIT during curricular time improved adolescents' CRF and several secondary outcomes. Our findings suggest B2L is unlikely to be an effective approach unless teachers embed sessions within the school day. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12618000293268).

Objective A systematic review on meatal cleaning prior to urinary catheterisation and post catheterisation and reduces the risk catheter-associated urinary tract infections (CAUTIs) and bacteriuria was published in 2017, with further studies undertaken since this time. The objective of this paper is to present an updated systematic review on the effectiveness of antiseptic cleaning of the meatal area for the prevention of CAUTIs and bacteriuria in patients who receive a urinary catheter. Design Systematic review. Data sources Electronic databases Cochrane Library, PubMed, Embase, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline and Academic Search Complete were searched from 1 January 2016 and 29 February 2020. Eligibility criteria Randomised controlled trials (RCTs) and quasi-experimental studies evaluating the use of antiseptic, antibacterial or non-medicated agents for cleaning the meatal, periurethral or perineal areas before indwelling catheter insertion or intermittent catheterisation or during routine meatal care. Data extraction and synthesis Data were extracted using the Cochrane Collaboration's data collection form for RCTs and non-RCTs. Data were extracted by one researcher and then checked for accuracy by a second researcher. Results A total of 18 studies were included. Some potential benefit of using antiseptics, compared with non-antiseptics for meatal cleaning to prevent bacteriuria and or CAUTI was identified (OR 0.84, 95% CI 0.69 to 1.02; p=0.071). Antiseptics (chlorhexidine or povidine-iodine) may be of value for meatal cleaning on the incidence of CAUTI, compared with comparator agents (saline, soap or antimicrobial cloths) (OR=0.65, 95% CI 0.42 to 0.99; p=0.047). Conclusion There is emerging evidence of the role of some specific antiseptics (chlorhexidine) prior to urinary catheterisation, in reducing CAUTIs, and some potential benefit to the role of antiseptics more generally in reducing bacteriuria. PROSPERO registration number CRD42015023741.

Background: Adverse childhood experiences have been linked to poor health and adverse health behavior in adulthood. Objective: This study aimed to estimate the prevalence of adverse childhood experiences among young Australian women (aged 20¿25) and examine associations between adverse childhood experiences and adult health behaviors and physical and mental health. Participants and Settings: Data were from the 1989-95 cohort of the Australian Longitudinal Study on Women's Health, who completed the Adverse Childhood Experiences Scale at Survey 3 in 2015 (N = 8609). Methods: Outcomes included: self-rated health, sexual health, psychological distress, depression, anxiety, suicide ideation, self-harm, substance abuse (drinking, smoking, illicit drugs), severe obesity, and exercise. Prevalence of childhood adversities were presented, with the association between childhood adversity and outcomes evaluated using log-binomial multivariable regressions (99% CI). Results: While 59% of women reported experiencing at least one childhood adversity, 10% of participants reported adverse childhood experiences across four or more categories, indicating a significant burden of risk for young Australian women. Women reporting four or more categories had higher rates of poor physical health (adjPR = 1.79, 99% CI = 1.51¿2.12), sexually transmitted infections (adjPR = 1.36, 99% CI = 1.11¿1.67), and poor mental health (adjPR = 2.78, 99% CI = 2.34¿3.32), and increased rates of severe obesity (adjPR = 2.14, 99% CI = 1.61¿2.86) and smoking (adjPR = 2.23, 99% CI = 1.89¿2.64). Conclusion: Using nationally representative data, this study shows adverse childhood experiences directly impact physical and mental health, and health behaviors in adulthood among young Australian women. The management of health and wellbeing in adulthood should look beyond the contemporaneous factors, incorporating a focus on how childhood adversity may negatively influence health behavior, health and wellbeing in later life.

Background: Interrupting prolonged sitting can attenuate postprandial glucose responses in overweight adults. The dose¿response effect in stroke survivors is unknown. The authors investigated the effects of interrupting 8 hours of prolonged sitting with increasingly frequent bouts of light-intensity standing-based exercises on the postprandial glucose response in stroke survivors. Methods: Within-participant, laboratory-based, dose-escalation trial. Participants completed three 8-hour conditions: prolonged sitting and 2 experimental conditions. Experimental conditions involved light-intensity standing-based exercises of increasing frequency (2 × 5 min to 6 × 5 min bouts). Postprandial glucose is reported. Results: Twenty-nine stroke survivors (aged 66 y) participated. Interrupting 8 hours of prolonged sitting with light-intensity standing-based exercises every 90 minutes significantly decreased postprandial glucose (positive incremental area under the curve; -1.1 mmol/L·7 h; 95% confidence interval, -2.0 to -0.1). In the morning (08:00¿11:00), postprandial glucose decreased during the 4 × 5 minutes and 6 × 5 minutes conditions (positive incremental area under the curve; -0.8 mmol/L·3 h; 95% confidence interval, -1.3 to -0.3 and -0.8 mmol/L·3 h; 95% confidence interval, -1.5 to -0.2, respectively) compared with prolonged sitting. Conclusion: Interrupting 8 hours of prolonged sitting at least every 90 minutes with light-intensity standing-based exercises attenuates postprandial glucose in stroke survivors. During the morning, postprandial glucose is attenuated when sitting is interrupted every 60 and 90 minutes.

Objectives Dizziness is a common and challenging clinical presentation in general practice. Failure to determine specific aetiologies can lead to significant morbidity and mortality. We aimed to establish frequency and associations of general practitioner (GP) trainees' (registrars') specific vertigo provisional diagnoses and their non-specific symptomatic problem formulations. Design A cross-sectional analysis of Registrar Clinical Encounters in Training (ReCEnT) cohort study data between 2010 and 2018. ReCEnT is an ongoing, prospective cohort study of registrars in general practice training in Australia. Data collection occurs once every 6 months midtraining term (for three terms) and entails recording details of 60 consecutive clinical consultations on hardcopy case report forms. The outcome factor was whether dizziness-related or vertigo-related presentations resulted in a specific vertigo provisional diagnosis versus a non-specific symptomatic problem formulation. Associations with patient, practice, registrar and consultation independent variables were assessed by univariate and multivariable logistic regression. Setting Australian general practice training programme. The training is regionalised and delivered by regional training providers (RTPs) (2010-2015) and regional training organisations (RTOs) (2016-2018) across Australia (from five states and one territory). Participants All general practice registrars enrolled with participating RTPs or RTOs undertaking GP training terms. Results 2333 registrars (96% response rate) recorded 1734 new problems related to dizziness or vertigo. Of these, 546 (31.5%) involved a specific vertigo diagnosis and 1188 (68.5%) a non-specific symptom diagnosis. Variables associated with a non-specific symptom diagnosis on multivariable analysis were lower socioeconomic status of the practice location (OR 0.94 for each decile of disadvantage, 95% CIs 0.90 to 0.98) and longer consultation duration (OR 1.02, 95% CIs 1.00 to 1.04). A specific vertigo diagnosis was associated with performing a procedure (OR 0.52, 95% CIs 0.27 to 1.00), with some evidence for seeking information from a supervisor being associated with a non-specific symptom diagnosis (OR 1.39, 95% CIs 0.92 to 2.09; p=0.12). Conclusions Australian GP registrars see dizzy patients as frequently as established GPs. The frequency and associations of a non-specific diagnosis are consistent with the acknowledged difficulty of making diagnoses in vertigo/dizziness presentations. Continuing emphasis on this area in GP training and encouragement of supervisor involvement in registrars' diagnostic processes is indicated.

Objective: To identify the optimal AUSDRISK threshold score to screen for pre-diabetes and diabetes. Methods: A total of 406 adult patients not diagnosed with diabetes were screened in General Practices (GP) between May and October 2019. All patients received a point of care (POC) HbA1c test. HbA1c test results were categorised into diabetes (=6.5% or =48 mmol/mol), pre-diabetes (5.7¿6.4% or 39¿47 mmol/mol), or normal (<5.7% or 39 mmol/mol). Results: Of these patients, 9 (2%) had undiagnosed diabetes and 60 (15%) had pre-diabetes. A Receiver Operator Characteristic (ROC) curve was constructed to predict the presence of pre-diabetes and diabetes; the area under the ROC curve was 0.72 (95%CI 0.65¿0.78) indicating modest predictive ability. The optimal threshold cut point for AUSDRISK score was 17 (sensitivity 76%, specificity 61%, + likelihood ratio (LR) 1.96, - likelihood ratio of 0.39) while the accepted cut point of 12 performed less well (sensitivity 94%, specificity 23%, +LR=1.22 -LR+0.26). Conclusions: The AUSDRISK tool has the potential to be used as a screening tool for pre-diabetes/diabetes in GP practices. A cut point of =17 would potentially identify 75% of all people at risk and three in 10 sent for further testing would be positive for prediabetes or diabetes. Implications for public health: Routine case-finding in high-risk patients will enable GPs to intervene early and prevent further public health burden from the sequelae of diabetes.

Introduction: Little is known about the joint effects of physical activity and sleep difficulties on hypertension. The aim of this study was to examine the joint associations of physical activity and sleep difficulties with the incidence of hypertension in mid-aged women. Study Design: Prospective cohort study. Main Outcome Measures: Mid-aged participants (n = 5,300) in the Australian Longitudinal Study on Women's Health completed four triennial surveys starting in 2004, when they had a mean age of 55 years. The presence of hypertension, physical activity and the number of sleep difficulties (range 0-4) were reported at each survey. Total MET.min/week of physical activity was assessed, and dichotomised as inactive (<500 MET.min/wk) or active (=500 MET.min/wk). Joint categories of physical activity and sleep difficulties were created using six mutually exclusive groups. Associations of joint physical activity and sleep difficulty groups with incident hypertension were examined via discrete-time survival analysis using logit-hazard models. Results: There were 1,175 cases of incident hypertension (22.2%). Compared with the Active and No Difficulties group, women in the Inactive and 1 Difficulty (Odds Ratio (95% confidence interval) (1.31 (1.06, 1.62)) and Inactive and 2-4 Difficulties (1.44 (1.16, 1.78)) groups were more likely to develop hypertension. Sleep difficulties were not associated with hypertension among active women. Conclusions: Mid-aged inactive women with sleep difficulties were more likely to develop hypertension. Physical activity appeared to protect against the increased risk of hypertension in women with sleeping difficulties.

Objective: To summarise the evidence regarding the impact of individualised music listening on persons with dementia. Methods: Six electronic databases (CINAHL, Medline, ProQuest, PsycINFO, Music Periodicals and Cochrane) were searched up to July 2018 for randomised controlled trials (RCTs) evaluating the efficacy of individualised music listening compared to other music and non¿music-based interventions. Results: Four studies were included. Results showed evidence of a positive impact of individualised music listening on behavioural and psychological symptoms of dementia (BPSDs) including agitation, anxiety and depression and physiological outcomes. Evidence for other outcomes such as cognitive function and quality of life was limited. Conclusions: The limited evidence suggests individualised music listening has comparable efficacy to more resource-intensive interventions. However, there was a small number of RCTs and some outcomes were evaluated by a single study. This limits the conclusions drawn, warranting more RCTs evaluating other outcomes beyond the BPSDs.

Background Poor sleep health is highly prevalent. Physical activity is known to improve sleep quality but not specifically targeted in sleep interventions. Purpose To compare the efficacy of a combined physical activity and sleep intervention with a sleep-only intervention and a wait-list control, for improving sleep quality in middle-aged adults without a diagnosed sleep disorder. Methods Three-arm randomized controlled trial (Physical Activity and Sleep Health (PAS), Sleep Health Only (SO), Wait-list Control (CON) groups; 3-month primary time-point, 6-month follow-up) of 275 (PAS = 110, SO = 110, CON = 55) inactive adults (40¿65 years) reporting poor sleep quality. The main intervention component was a smartphone/tablet "app" to aid goal setting and self-monitoring physical activity and/or sleep hygiene behaviors (including stress management), and a pedometer for PAS group. Primary outcome was Pittsburgh Sleep Quality Index (PSQI) global score. Secondary outcomes included several self-reported physical activity measures and PSQI subcomponents. Group differences were examined stepwise, first between pooled intervention (PI = PAS + SO) and CON groups, then between PAS and SO groups. Results Compared with CON, PI groups significantly improved PSQI global and subcomponents scores at 3 and 6 months. There were no differences in sleep quality between PAS and SO groups. The PAS group reported significantly less daily sitting time at 3 months and was significantly more likely to report =2 days/week resistance training and meeting physical activity guidelines at 6 months than the SO group. Conclusions PIs had statistically significantly improved sleep quality among middle-aged adults with poor sleep quality without a diagnosed sleep disorder. The adjunctive physical activity intervention did not additionally improve sleep quality.

Background: Emerging evidence links a poor diet with mental ill-health although the direction of this association is unclear. The aim was to examine the bidirectional prospective relationships between core (and non-core food consumption, and symptoms of depression. Methods: Depressive symptoms (Mental Health Index-5, MHI-5), current/prior depression and consumption of core (recommended food groups) and non-core (discretionary) foods were assessed in the population-based 2013 and 2017 Household Income and Labour Dynamics in Australia cohort study. Three cross-lagged linear models assessed associations between all three baseline variables in 2013, alternating 2017 variables as outcomes. Results: In the population (n = 10,003; 48.3% women; 48.5[15.7] years), core food score in 2013 was associated with MHI-5 (ß:0.102, 95%CI: 0.010,0.193) in 2017, while the non-core food score was not (ß:-0.030, 95%CI:-0.099,0.160). Depressive symptom score in 2013 was not associated with either food score in 2017. Current/prior diagnosis of depression in 2013 was associated with core (ß:-0.198, 95%CI:-0.329,-0.067) but not non-core (ß:-0.036, 95%CI: -0.151,0.080) food score in 2017. Limitations: Results may not be generalizable to the whole population due to some selection bias, self-report depression diagnosis may have led to misclassification of previous mental illness, and core and non-core food scores are not validated measures of diet quality. Conclusions: There is a prospective association between core food consumption and depressive symptoms. This association is of small magnitude and we cannot discount insufficient core food consumption reflecting an effect of prior mental illness. Our results suggest that, for depression, public health focus should be on improving core food intake.

Objectives: Supporting healthy ageing is a key priority worldwide. Physical activity, diet quality and sleep are all associated with health outcomes, but few studies have explored their independent associations with all-cause mortality in an older population in the same model. The study aim was to examine associations between step-count, self-reported diet quality, restless sleep, and all-cause mortality in adults aged 55¿85 years. Design: A prospective cohort study of adults in Newcastle, New South Wales, Australia. Method: Data were from 1697 participants (49.3% women; baseline mean age 65.4 ± 7.1 years). Daily steps (measured by pedometer), diet quality (from a modified Australian Recommended Food Score), and frequency of restless sleep (by self-report) were assessed in relation to all-cause mortality using Cox proportional hazard regression with adjustment for sex, age, household income and smoking. Baseline data were collected between January 2005 and April 2008, and last follow-up was in March 2017 (median follow-up 9.6 years). Results: Higher step count (HR: 0.93, 95%CI: 0.88¿0.98 per 1000-step increment) and higher diet quality (HR: 0.86, 95%CI: 0.74¿0.99 per 8-point increment in diet quality score) were associated with reduced mortality risk. Restless sleep for =3 nights/week was not associated with mortality risk (HR: 1.03, 95%CI: 0.78¿1.39). Sensitivity analyses, adjusting for chronic disease and excluding deaths <1 year after baseline, did not change these estimates. Conclusions: Increased daily steps and consumption of a greater variety of nutrient-dense foods every week would result in substantial health benefits for older people. Future research should include a greater variety of sleep measures.

Background: General practitioners play an important role in diagnosis and ongoing management of pregnancies. Some GP registrars entering GP training may have had no post-graduate experience in obstetrics and gynaecology. GP registrars' involvement in antenatal care is under-researched. Aims: This study aimed to determine the prevalence and associations of Australian GP registrars' clinical consultations involving antenatal care. Materials and Methods: A cross-sectional analysis from the Registrar Clinical Encounters in Training (ReCEnT) cohort study. GP registrars record details of 60 consecutive consultations during each of three six-month training terms. Associations of managing pregnancy-related problems (compared to all other problems) were analysed using univariate and multivariable logistic regression. Independent variables included registrar, practice, patient, consultation and educational factors. Results: Antenatal care comprised 3277 (1.1%) of registrar problems/diagnoses. Consultations involving pregnancy-related problems were significantly associated with registrars being female, in term three, younger, and having post-graduate qualifications in obstetrics/gynaecology. Patients were significantly more likely to be from a non-English speaking background. Pregnancy-related problems/diagnoses were more likely to be seen in lower socioeconomic areas. Consultation factors significantly associated with a pregnancy-related problem/diagnosis included ordering imaging, ordering pathology, arranging referrals, and a longer duration of consultation. Registrars were less likely to prescribe medication or generate learning goals. Conclusions: GP registrars see fewer antenatal problems compared to established GPs. Male registrars, especially, have significantly less exposure to antenatal care, suggesting potential limitation of opportunity to gain skills and experience in antenatal care.

The impact of pre-pregnancy obesity and maternal diet quality on the use of healthcare resources during the perinatal period is underexplored. We assessed the effects of body mass index (BMI) and diet quality on the use of healthcare resources, to identify whether maternal diet quality may be effectively targeted to reduce antenatal heath care resource use, independent of women's BMI. Cross-sectional data and inpatient medical records were gathered from pregnant women attending publicly funded antenatal outpatient clinics in Newcastle, Australia. Dietary intake was self-reported, using the Australian Eating Survey (AES) food frequency questionnaire, and diet quality was quantified from the AES subscale, the Australian Recommended Food Score (ARFS). Mean pre-pregnancy BMI was 28.8 kg/m2 (range: 14.7 kg/m2¿64 kg/m2). Mean ARFS was 28.8 (SD = 13.1). Higher BMI was associated with increased odds of caesarean delivery; women in obese class II (35.0¿39.9 kg/m2) had significantly higher odds of caesarean delivery compared to women of normal weight, (OR = 2.13, 95% CI 1.03 to 4.39; p = 0.04). Using Australian Refined Diagnosis Related Group categories for birth admission, the average cost of the birth admission was $1348 more for women in the obese class II, and $1952 more for women in the obese class III, compared to women in a normal BMI weight class. Higher ARFS was associated with a small statistically significant reduction in maternal length of stay (RR = 1.24, 95% CI 1.00, 1.54; p = 0.05). There was no evidence of an association between ARFS and mode of delivery or "midwifery-in-the-home-visits".

Diet quality, physical activity, alcohol use, smoking, sleep and sitting-time are behaviors known to influence health. The aims of this study were to identify how these behaviors co-occur to form distinct health-behavior patterns, and to investigate the relationship between these patterns, and mental and self-rated health. Members of the Australian 10,000 Steps project were invited to participate in an online survey in November¿December 2011. The participants self-reported demographic and behavioral characteristics (fruit and vegetable intake, fast food, soft drink and alcohol consumption, smoking, physical activity, sitting-time and sleep), frequency of mental distress and self-rated health. Latent Class Analysis was used to identify health-behavior patterns. Latent class regression was used to examine relationships between behavior patterns, mental and self-rated health, and socio-demographic and economic factors. Data were analyzed in October 2017. Complete datasets were obtained from 10,638 participants. Four latent classes were identified, characterized by 'Low-Risk Behavior', 'Poor Sleep, Low-Risk Daytime Behavior', 'sound Sleep, High-Risk Daytime Behavior' and 'High-Risk Behavior'. The latter two classes, both characterized by high-risk daytime behaviors, were associated with poor self-rated health. Participants in classes with high-risk daytime behaviors were more likely to be younger, non-partnered, non-university educated, from lower income households and work longer hours. Classes characterized by poor sleep quality were associated with higher frequency of mental distress. Findings suggest that experiencing poor sleep is partly independent of daytime behaviors, demographic and socioeconomic factors, but has a strong association with mental health.

Patients with mental health conditions commonly present in General Practice. Mental health curricula are broad. We do not know that trainees are exposed to the learning they require. This study aimed to establish the prevalence, characteristics and associations of GP trainees' management of mental health problems. This paper presents a cross-sectional analysis of the Registrar Clinical Encounters in Training (ReCEnT) study, an ongoing multisite cohort study of Australian GP trainees (registrars) documenting their clinical experiences over 60 consecutive consultations. Univariate and multivariable logistic regression analyses were conducted with outcome of the problem/diagnosis being a mental health condition. 1659 trainees provided data on 218,325 consultations and 340,453 problems/diagnoses. Mental health conditions were associated with patients being male, of Aboriginal or Torres Strait Islander or English-speaking background. Trainee characteristics were being more senior and having trained in Australia. Practice characteristics included being in low socioeconomic areas. Trainees sought less help for mental health concerns than they did for other problems. While early-career GPs see a broad range of mental health conditions, they may benefit from training to manage patients from cross-cultural contexts. They may also need support to generate appropriate learning goals and seek assistance if they are to continue to deepen competence.

Introduction: E-cigarette use is controversial worldwide. The majority of previous studies on e-cigarette use were not gender specific. This study aimed to identify the predictors of e-cigarette use among young Australian women. Methods: This study used cross-sectional data from the 1989¿1995 cohort of the Australian Longitudinal Study on Women's Health. In 2015, study participants (N=8,915) aged 19¿26 years completed an online survey. Multivariable logistic regression was used to identify predictors of e-cigarette use. Data were analyzed in 2018. Results: The prevalence of ever and past-year e-cigarette use among young Australian women was 11.1% and 6.4%, respectively. More than a quarter of past-year and ever e-cigarette users were never cigarette smokers. Use of e-cigarettes in the past year was associated with younger age (AOR per year increase=0.87, 95% CI=0.82, 0.93); financial difficulty (AOR=0.68, 95% CI=0.54, 0.87); being an ex-smoker (AOR=5.05, 95% CI=3.64, 7.01) or current cigarette smoker (AOR=10.01, 95% CI=7.77, 12.89); drinking at a level of lifetime risk of harm from alcohol-related disease or injury (AOR=1.23, 95% CI=1.01, 1.53). Ever e-cigarette use showed similar associations and was also associated with rural residence (AOR=0.74, 95% CI=0.60, 0.91) and intimate partner violence (AOR=1.44, 95% CI=1.17, 1.76). Conclusions: The high prevalence of e-cigarette use among never cigarette smokers has significant public health implications. Interventions to curb the use of e-cigarettes among young Australian women should focus on risk factors, such as early age, cigarette smoking, alcohol use, and intimate partner violence.

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.

BACKGROUND AND OBJECTIVES: Acne is a common chronic condition. The aim of this study was to establish the frequency and associations of consultations for acne by early-career general practitioners (general practice registrars). METHOD: The study was a cross-sectional analysis of data from the Registrar Clinical Encounters in Training study. RESULTS: During 2010-18, 2234 registrars contributed data for 289,594 consultations and 453,344 problems/diagnoses. Acne comprised 0.38% (95% confidence interval [CI]: 0.36, 0.40) of all problems/diagnoses. Nine per cent of patients were new to the practice (odds ratio [OR] 1.82; 95% CI: 1.62, 2.05) and 61% were existing patients of the practice but new to the registrar (OR 1.78; 95% CI: 1.46, 2.18). There was a lower frequency of acne presentations by Aboriginal and Torres Strait Islander patients (OR 0.29; 95% CI: 0.14, 0.58) and by patients in regional/remote/very remote areas (OR 0.75; 95% CI: 0.58, 0.95). DISCUSSION: The majority of the patients had an existing diagnosis of acne. That Aboriginal and Torres Strait Islander patients and patients in rural/remote areas present less frequently with acne requires further study.

Background: The obesity-cataract association has been inconsistently reported. The fat mass and obesity-related (FTO) single-nucleotide polymorphism (SNP) rs9939609 is a major SNP associated with obesity and has been used as an instrumental variable for obesity in a Mendelian randomization (MR) approach. An interaction between the FTO SNP and macronutrient intake for obesity was suggested previously. Objective: The aim of this study was to assess the associations between obesity and cataract, using FTO SNP rs9939609 as an instrumental variable in an MR approach, and explore interactions of this SNP with macronutrient intake in relation to risk of cataract in a population-based cohort. Methods: The Blue Mountains Eye Study (BMES) is a longitudinal population-based study of common eye disease. Of 3654 baseline participants of the BMES (1992-1994), 2334 (75.8% of survivors) and 1952 (76.7% of survivors) were followed 5 and 10 y later. During the 5-y follow-up, 1174 new participants were examined. Cumulative cataract was defined as the presence of cortical, nuclear, or posterior subcapsular (PSC) cataract at any visit, following the Wisconsin Cataract Grading System. Imputed dosage of the FTO SNP rs9939609 was used. Quintiles of macronutrient intake (carbohydrates, protein, fats) were derived from an FFQ. ORs and 95% CIs were estimated using multivariable-adjusted logistic regression models. Results: After multivariable adjustment, there were no associations between BMI and any cataract types in MR models using rs9939609 as an instrumental variable. However, an interaction between rs9939609 and protein intake for PSC cataract risk was suggested (P = 0.03). In analyses stratified by quintiles of protein intake, each minor allele of rs9939609 was associated with increased odds of PSC (OR: 2.14; 95% CI: 1.27, 3.60) in the lowest quintile subgroup only. Conclusions: Obesity was not causally associated with age-related cataract. However, among persons in the lowest quintile of protein intake, obesity may be associated with PSC cataract.

Objective: Limited international evidence suggests general practice registrars' emergency department (ED) referral rates exceed those of established general practitioners (GPs). The aim of the present study was to fill an evidence gap by establishing the prevalence, nature and associations of Australian GP registrar ED referrals. Methods: A cross-sectional analysis was performed of the Registrar Clinical Encounters in Training (ReCEnT) cohort study of GP registrars' consultation experiences, between 2010 and 2015. The outcome factor in logistic regression analysis was referral to an ED. Independent variables included patient-level, registrar-level, practice-level and consultation-level factors. Results: In all, 1161 GP registrars (response rate 95.5%) contributed data from 166 966 consultations, comprising 258 381 individual problems. Based on responses, 0.5% of problems resulted in ED referral, of which nearly 25% comprised chest pain, abdominal pain and fractures. Significant (P < 0.05) associations of ED referral included patient age <15 and >34 years, the patient being new to the registrar, one particular regional training provider (RTP), in-consultation information or assistance being sought and learning goals being generated. Outer regional-, remote-or very remote-based registrars made significantly fewer ED referrals than more urban registrars. Of the problems referred to the ED, 45.5% involved the seeking of in-consultation information or assistance, predominantly from supervisors. Conclusions: Registrars' ED referral rates are nearly twice those of established GPs. The findings of the present study suggest acute illnesses or injuries present registrars with clinical challenges and real learning opportunities, and highlight the importance of continuity of care, even for acute presentations. What is known about the topic?: A GP's decision concerning continued community-versus hospital-based management of acute presentations demands careful consideration of a suite of factors, including implications for patient care and resource expenditure. General practice vocational training is a critical period for the development of GP registrars' long-term patterns of practice. Although limited international evidence suggests GP registrars and early career GPs refer patients to the ED at a higher rate than their more experienced peers, these studies involved small subject numbers and did not investigate associations of registrars making an ED referral. Relevant Australian studies focusing on GP registrars' ED referral patterns are lacking. What does this paper add?: The present ongoing cohort study is the first to establish the patterns of ED referrals made by Australian GP registrars, encompassing five general practice RTPs across five states, with participating registrars practising in urban, rural, remote and very remote practices. Several significant associations were found with GP registrars making ED referrals, including patient age, continuity of care, the registrar's RTP, assistance sought by the registrar and rurality of the registrar's practice. What are the implications for practitioners?: The higher likelihood of GP registrars seeing acute presentations than their more established practice colleagues, coupled with a demonstrated association of registrars seeking in-consultation assistance for such presentations, highlights the importance of GP supervisor accessibility in facilitating ED referral appropriateness and in the development of registrars' safe clinical practice.

Purpose: To explore whether there was a difference in objectively measured physical activity and study participation between people who received their preferred study group allocation (matched) and those who did not receive their preferred study group (mismatched). Design: Secondary data from the NewCOACH randomized controlled trial. Setting: Insufficiently active patients in the primary care settings in Sydney and Newcastle, Australia. Participants: One hundred seventy-two adults aged 20 to 81 years. Intervention: Participants indicated their intervention preference at baseline for (1) five face-to-face visits with an exercise specialist, (2) one face-to-face visit and 4 telephone follow-ups with an exercise specialist, (3) written material, or (4) slight-to-no preference. Participants were then allocated to an intervention group and categorized as either "matched" or "mismatched" based on their indications. Participants who reported a slight-to-no preference was categorized as "matched." Measures: Daily step count as measured by pedometers and study participation. Analysis: Mean differences between groups in daily step count at 3 and 12 months (multiple linear regression models) and study participation at baseline, 3 months, and 12 months (¿2 tests). Results: Preference for an intervention group prior to randomization did not significantly (all P's >.05 using 95% confidence interval) impact step counts (differences of <600 steps/day between groups) or study participation. Conclusion: Future research should continue to address whether the strength of preferences influence study outcome and participation and whether the study preferences change over time.

Importance: Genome-wide association studies (GWASs) in European populations have identified more than 100 schizophrenia-associated loci. A schizophrenia GWAS in a unique Indian population offers novel findings. Objective: To discover and functionally evaluate genetic loci for schizophrenia in a GWAS of a unique Indian population. Design, Setting, and Participants: This GWAS included a sample of affected individuals, family members, and unrelated cases and controls. Three thousand ninety-two individuals were recruited and diagnostically ascertained via medical records, hospitals, clinics, and clinical networks in Chennai and surrounding regions. Affected participants fulfilled DSM-IV diagnostic criteria for schizophrenia. Unrelated control participants had no personal or family history of psychotic disorder. Recruitment, genotyping, and analysis occurred in consecutive phases beginning January 1, 2001. Recruitment was completed on February 28, 2018, and genotyping and analysis are ongoing. Main Outcomes and Measures: Associations of single-nucleotide polymorphisms and gene expression with schizophrenia. Results: The study population included 1321 participants with schizophrenia, 885 family controls, and 886 unrelated controls. Among participants with schizophrenia, mean (SD) age was 39.1 (11.4) years, and 52.7% were male. This sample demonstrated uniform ethnicity, a degree of inbreeding, and negligible rates of substance abuse. A novel genome-wide significant association was observed between schizophrenia and a chromosome 8q24.3 locus (rs10866912, allele A; odds ratio [OR], 1.27 [95% CI, 1.17-1.38]; P = 4.35 × 10-8) that attracted support in the schizophrenia Psychiatric Genomics Consortium 2 data (rs10866912, allele A; OR, 1.04 [95% CI, 1.02-1.06]; P = 7.56 × 10-4). This locus has undergone natural selection, with the risk allele A declining in frequency from India (approximately 72%) to Europe (approximately 43%). rs10866912 directly modifies the abundance of the nicotinate phosphoribosyltransferase gene (NAPRT1) transcript in brain cortex (normalized effect size, 0.79; 95% CI, 0.6-1.0; P = 5.8 × 10-13). NAPRT1 encodes a key enzyme for niacin metabolism. In Indian lymphoblastoid cell lines, (risk) allele A of rs10866912 was associated with NAPRT1 downregulation (AA: 0.74, n = 21; CC: 1.56, n = 17; P =.004). Preliminary zebrafish data further suggest that partial loss of function of NAPRT1 leads to abnormal brain development. Conclusions and Relevance: Bioinformatic analyses and cellular and zebrafish gene expression studies implicate NAPRT1 as a novel susceptibility gene. Given this gene's role in niacin metabolism and the evidence for niacin deficiency provoking schizophrenialike symptoms in neuropsychiatric diseases such as pellagra and Hartnup disease, these results suggest that the rs10866912 genotype and niacin status may have implications for schizophrenia susceptibility and treatment..

Background: Low birthweight is more common in infants of indigenous (Aboriginal and/or Torres Strait Islander) than of White Australian mothers. Controversy exists on whether fetal growth is normally different in different populations. Objective: We sought to determine the relationships of birthweight, birthweight percentiles, and smoking with perinatal outcomes in indigenous vs nonindigenous infants to determine whether the White infant growth charts could be applied to indigenous infants. Study Design: Data were analyzed for indigenous status, maternal age and smoking, and perinatal outcomes in 45,754 singleton liveborn infants of at least 20 weeks gestation or 400 g birthweight delivered in New South Wales, Australia, between June 2010 and July 2015. Results: Indigenous infants (n=6372; 14%) had a mean birthweight 67 g lower than nonindigenous infants (P<.0001; with adjustment for infant sex and maternal body mass index). Indigenous mean birthweight percentile was 4.2 units lower (P<.0001). Adjustment for maternal age, smoking, body mass index, and infant sex reduced the difference in birthweight/percentiles to nonsignificance (12 g; P=.07). Conclusion: Disparities exist between indigenous and non-indigenous Australian infants for birthweight, birthweight percentile, and adverse outcome rates. Adjustment for smoking and maternal age removed any significant difference in birthweights and birthweight percentiles for indigenous infants. Our data indicate that birthweight percentiles should not be adjusted for indigenous ethnicity because this normalizes disadvantage; because White and indigenous Australians have diverged for approximately 50,000 years, it is likely that the same conclusions apply to other ethnic groups. The disparities in birthweight percentiles that are associated with smoking will likely perpetuate indigenous disadvantage into the future because low birthweight is linked to the development of chronic noncommunicable disease and poorer educational attainment; similar problems may affect other indigenous populations.

Objectives: We examined the development of disease and disability in a large cohort of older women, the extent to which these conditions exempt them from being classified as successful agers and different trajectories of disease, disability and longevity across women's later life. Methods: We used survey data from 12,432 participants of the 1921-26 birth cohort of the Australian Longitudinal Study of Women's Health from 1996 (age 70-75) to 2016 (age 90-95). Repeated measures latent class analysis (RMLCA) identified trajectories of the development of disease with or without disability and according to longevity. Bivariate analyses and multivariable multinomial logistic regression models were used to examine the association between participants' baseline characteristics and membership of the latent classes. Results: Over one-third of women could be considered to be successful agers when in their early 70s, few women could still be classified in this category throughout their later life or by the end of the study when they were in their 90s (~1%). RMLCA identified six trajectory groups including managed agers long survivors (9.0%) with disease but little disability, usual agers long survivors (14.9%) with disease and disability, usual agers (26.6%) and early mortality (25.7%). A small group of women having no major disease or disability well into their 80s were identified as successful agers (5.5%). A final group, missing surveys (18.3%), had a high rate of non-death attrition. Groups were differentiated by a number of social and health factors including marital status, education, smoking, body mass index, exercise and social support. Conclusions: The study shows different trajectories of disease and disability in a cohort of ageing women, over time and through to very old ages. While some women continue into very old age with no disease or disability, many more women live long with disease but little disability, remaining independent beyond their capacity to be classified as successful agers.

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (|r^ g| ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.

Introduction: Having a low level of physical activity is an established risk factor for stroke, but little is known about the importance of common sedentary behavior¿television viewing¿to stroke risk. Methods: We conducted a retrospective analysis of data that were collected as part of the longitudinal Australian Diabetes, Obesity, and Lifestyle study. Stroke events reported during the study (between baseline assessment in 1999-2000 and April 2011) were confirmed using adjudication based on medical records. Baseline data on minutes per week spent watching television were used as the exposure variable. Other variables were collected in assessments at wave 2 (2004-05) and wave 3 (2011-2012). Univariable and multivariable logistic regression analyses were performed. Results: Among the full Australian Diabetes, Obesity, and Lifestyle study population (n = 11,247), there were 153 participants with confirmed stroke during the study period, and 9207 participants with no stroke in this period. Participants who went on to have their first stroke during the study had significantly higher levels of TV viewing time at baseline than those who did not have a stroke (P =.001). This association was not present (P =.83), however, when age and sex were included in the regression model. Conclusion: In the Australian Diabetes, Obesity, and Lifestyle study dataset, there was no evidence that more TV viewing is independently associated with risk of stroke, although analyses may have been underpowered.

Background: In Australia, more than 50% of end-stage kidney disease patients start haemodialysis treatment with a central venous catheter (CVC). While there are benefits of CVC access, they are associated with a high risk of bacteraemia infection. National guidelines for prevention of catheter-related infections advocate the importance of hand hygiene and asepsis practices, and for this reason, many dialysis units have regular auditing on hand hygiene and aseptic technique. Aim: To report the relationship between hygiene audit results and infection rates in our facility. Method: A hygiene audit tool was developed with 17 hygiene measures, categorised into three domains: environment, aseptic technique, and dressing care. This tool was used to observe nursing staff's hand hygiene compliance and aseptic technique during CVC care across five regional and remote units. Audit results were collected from 2011 to 2015. Results: A total of 350 audits were analysed, and the overall hygiene compliance was consistently high (85-99%). The relationship between mean hygiene score and infection rates was negative and the association was non-significant (p=0.7). Conclusion: The overall infection rates have decreased in our facility, by an average of 76% across sites. The decrease in infection was correlated to interventions such as minimising catheter utilisation, implementation of antimicrobial dressings and streamlining protocols but not hygiene audit results. Good hygiene is fundamental in the care of a CVC; however, whilst all facilities should strive for excellent audit results, it should not be the sole focus to prevent catheter infection.

Objective: Interventions to promote physical activity for sedentary patients seen in general practice may be a way to reduce the burden of chronic disease. Coaching by an exercise physiologist is publicly funded in Australia, but cost effectiveness has not been documented. Methods: In a three-arm randomised controlled trial, face-to-face coaching and telephone coaching over 12 weeks were compared with a control group using the outcome of step count for one week at baseline, three months and twelve months. Program costs and time-based costs were considered. Quality of life was measured as a secondary outcome. Results: At 12 months, the intervention groups were more active than controls by 1,002 steps per day (95%CI 244, 1,759). This was achieved at a cost of AUD$245 per person. There was no change in reported quality of life or utility values. Conclusion: Coaching achieved a modest increase in activity equivalent to 10 minutes walking per day, at a cost of AUD$245 per person. Face-to-face and telephone counselling were both effective. Implication for public health: Persistence of increases nine months after the end of coaching suggests it creates long-term change and is a good value health intervention.

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11¿13% of the variance in educational attainment and 7¿10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

Australian general practitioners (GPs) commonly manage dermatological conditions requiring procedures. GP registrars have limited pre-vocational training exposure to dermatology and find skin problems challenging. We aimed to establish the prevalence, nature and associations of GP registrars' performance of skin procedures. We conducted a cross-sectional analysis from the Registrar Clinical Encounters in Training cohort study. Multivariable logistic regression was used to establish associations of our outcome (skin procedures, both including and excluding cryotherapy). Independent variables included patient and doctor demographics, diagnoses/problems managed and registrars' recourse to in-consultation assistance/information. A total of 1161 registrars provided data on 166,988 consultations, recording 2927 skin procedures (16.7% of all procedures; performed in 1.7% of consultations). Cryotherapy, excision, punch biopsy and shave biopsy were most common. More complex procedures were performed infrequently. Significant associations of performing procedures included rural/remote location (compared to major city), male patients, patient age 65+ (compared to age 15¿34) and registrars seeking in-consultation information/assistance. Skin procedures were less likely for Aboriginal patients or those from non-English-speaking backgrounds. For non-cryotherapy procedures, rurality was not significantly associated, but significant differences were found between training regions. In summary, GP registrars perform fewer dermatological procedures compared to established GPs. Findings will inform GP vocational training in skin procedures.

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

Objectives. Expanding learner cohorts of medical students and general practitioner (GP) vocational trainees and the impending retirement of the 'baby boomer' GP cohort threaten the teaching and supervisory capacity of the Australian GP workforce. Engaging newly qualified GPS is essential to sustaining this workforce training capacity. The aim of the present study was to establish the prevalence and associations of in-practice clinical teaching and supervision in early career GPS. Methods. The present study was a cross-sectional questionnaire-based study of recent (within 5 years) alumni of three of Australia's 17 regional general practice training programs. The outcome factor was whether the alumnus taught or supervised medical students, GP registrars or other learners in their current practice. Logistic regression analysis was used to establish associations of teaching and supervision with independent variables comprising alumnus demographics, current practice characteristics and vocational training experiences. Results. In all, 230 alumni returned questionnaires (response rate 37.4%). Of currently practising alumni, 52.4% (95% confidence interval (CI) 45.6-59.0%) reported current teaching or supervisory activities. Factors significantly (P < 0.05) associated with alumni currently undertaking in-practice clinical teaching and supervision were: Australian medical graduation (odds ratio (OR) for international graduates 0.36; 95% CI 0.14-0.92), working in a regional or remote area (OR 2.75; 95% CI 1.24-6.11) and currently undertaking nursing home visits, home visits or after-hours work (OR 2.01; CI 1.02-3.94).

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

Background: The pneumococcal polysaccharide vaccine (PPV) has been associated with reduced risk of cardiovascular events in human observational studies. Animal studies suggest that the phosphorylcholine epitope in the Streptococcus pneumoniae cell wall is structurally similar to oxidized low-density lipoprotein (oxLDL), hence PPV induces the production of antibodies that cross-react with anti-oxLDL and may cause regression of atherosclerotic plaque. We set out to determine the strength of association between PPV administration and reduction in cardiovascular events. Methods: A longitudinal, population-based cohort study of older Australians, from the Hunter Community Study, with up to 11 years of follow-up. We included participants aged = 65 years at baseline (2004¿2008), without a history of cardiovascular disease (CVD). History of PPV administration at baseline was the main exposure of interest. "Total number of hospital bed-days with CVD primary diagnosis" was one of the main outcomes measured. Models were adjusted for age, diabetes, alcohol intake, and smoking status. Influenza vaccine was the control exposure used and fracture bed-days was the control outcome used, to investigate the potential for residual confounding. Results: 91 of the total 1074 participants (mean age = 72, male = 45%) experienced a CVD event during follow-up. PPV (regardless of influenza vaccine) was associated with a significant reduction in CVD bed-day, (n = 863, incident rate ratio, IRR = 0.65, 95%CI: 0.45¿0.94, p = 0.02), but influenza vaccine (regardless of PPV) was not (n = 864, IRR = 0.86, 95%CI: 0.54¿1.35, p = 0.51). Furthermore, PPV adjusted for influenza vaccine remained associated with CVD bed-days (IRR = 0.64, 95%CI: 0.43¿0.96, p = 0.03) but was not associated with fracture bed-days (IRR = 0.75, 95%CI: 0.28¿2.00, p = 0.56). Conclusion: PPV demonstrated a 35% reduction in CVD bed-days. This finding was robust to residual confounding, using a control exposure and a control outcome, eliminating the concern for healthy-user bias. A large double-blinded placebo-controlled RCT is underway to confirm our finding and to explore the proposed mechanism of action (ACTRN12615000536561).

Background and Purpose - This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue =3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. Methods - This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of =60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). Results - A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P<0.001) and improved quality of life (SSQoL, 11.81; 95% CI, 2.31 to 21.31; P=0.0148) compared with placebo. Montreal cognitive assessment and DASS were not significantly improved with modafinil therapy during the study period (P>0.05). Conclusions - Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil.

This study analyzed clinically actionable pharmacogenotypes for clopidogrel, warfarin, statins, thiopurines, and tacrolimus using microarray data for 2121 participants (55¿85 years) from the Australian Hunter Community Study (HCS). At least 74% of participants (95% confidence interval [CI]: 72%¿76%) had strong level evidence for at least one medium- or high-risk actionable genotype that would trigger a change in standard therapy under current international recommendations. About 14% of these participants (95% CI: 12%¿16%) were taking medication potentially affected by the genotype in question. Furthermore, ~2.6% of all participants with medication data (95% CI: 1.4%¿3.8%) had a high-risk clinically actionable genotype for a medication to which they were exposed. This represents a considerable number of people at the population level. Although relationships between genotype and health outcomes remain contentious, pharmacogenotyping of multiple variants simultaneously may have considerable potential to improve medication safety and efficacy for older people in the community.

Objective: To assess the number of pathology tests ordered by general practice registrars during their first 18e24 months of clinical general practice. Design: Longitudinal analysis of ten rounds of data collection (2010e2014) for the Registrar Clinical Encounters in Training (ReCEnT) study, an ongoing, multicentre, cohort study of general practice registrars in Australia. The principal analysis employed negative binomial regression in a generalised estimating equations framework (to account for repeated measures on registrars). Setting, participants: General practice registrars in training posts with five of 17 general practice regional training providers in five Australian states. The registrar participation rate was 96.4%. Main outcome measure: Number of pathology tests requested per consultation. The time unit foranalysiswas the registrar training term (the 6-month full-time equivalent component of clinical training); registrars contributed data for up to four training terms. Results: 876 registrars contributed data for 114 584 consultations. The number of pathology tests requested increased by 11% (95% CI, 8e15%; P < 0.001) per training term. Conclusions: Contrary to expectations, pathology test ordering by general practice registrars increased significantly during their first 2 years of clinical practice. This causes concerns about overtesting. As established general practitioners order fewer tests than registrars, test ordering may peak during late vocational training and early career practice. Registrars need support during this difficult period in the development of their clinical practice patterns.

Context: Tolerance for ambiguity is essential for optimal learning and professional competence. General practice trainees must be, or must learn to be, adept at managing clinical uncertainty. However, few studies have examined associations of intolerance of uncertainty in this group. Objectives: The aim of this study was to establish levels of tolerance of uncertainty in Australian general practice trainees and associations of uncertainty with demographic, educational and training practice factors. Methods: A cross-sectional analysis was performed on the Registrar Clinical Encounters in Training (ReCEnT) project, an ongoing multi-site cohort study. Scores on three of the four independent subscales of the Physicians' Reaction to Uncertainty (PRU) instrument were analysed as outcome variables in linear regression models with trainee and practice factors as independent variables. Results: A total of 594 trainees contributed data on a total of 1209 occasions. Trainees in earlier training terms had higher scores for 'Anxiety due to uncertainty', 'Concern about bad outcomes' and 'Reluctance to disclose diagnosis/treatment uncertainty to patients'. Beyond this, findings suggest two distinct sets of associations regarding reaction to uncertainty. Firstly, affective aspects of uncertainty (the 'Anxiety' and 'Concern' subscales) were associated with female gender, less experience in hospital prior to commencing general practice training, and graduation overseas. Secondly, a maladaptive response to uncertainty (the 'Reluctance to disclose' subscale) was associated with urban practice, health qualifications prior to studying medicine, practice in an area of higher socio-economic status, and being Australian-trained. Conclusions: This study has established levels of three measures of trainees' responses to uncertainty and associations with these responses. The current findings suggest differing 'phenotypes' of trainees with high 'affective' responses to uncertainty and those reluctant to disclose uncertainty to patients. More research is needed to examine the relationship between clinical uncertainty and clinical outcomes, temporal changes in tolerance for uncertainty, and strategies that might assist physicians in developing adaptive responses to clinical uncertainty.

Aims We compared the impact of new gestational diabetes (GDM) diagnostic criteria by IADPSG with previous criteria to ascertain concordance between the two criteria; and whether women discordant for GDM between the old and new criteria had increased pregnancy complications. Methods Oral glucose tolerance tests of pregnant women across time periods using old criteria and new criteria were collected. Maternal data and perinatal outcomes were compared between diagnostic concordant and discordant women. Results In total, 666/5178 (12.9%) women were diagnosed and treated for GDM. There was a significant increase in odds of any complication in concordant positive women (OR 3.91 95%CI 2.71¿5.63, p <.0001); in women only positive by new GDM criteria (OR 2.06, 95% CI 1.41¿2.99, p =.0002); and women only positive by old GDM criteria (OR 2.28, 95% CI 1.42¿3.66, p =.0006); compared to concordant negative women. This is mainly due to macrosomia and nursery admissions. Conclusion This study confirms that women diagnosed with GDM on both old and new criteria have a higher rate of birth complications than women without GDM. Women who have been missed out due to new criteria may still be at risk. Therefore, combination of both old and new criteria may be optimal for identifying high-risk pregnancies.

Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3?-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis.

We aimed to evaluate the effect of pain education on opioid prescribing by early-career general practitioners. A brief training workshop was delivered to general practice registrars of a single regional training provider. The workshop significantly reduced hypothetical opioid prescribing (in response to paper-based vignettes) in an earlier evaluation. The effect of the training on actual prescribing was evaluated using a nonequivalent control group design nested within the Registrar Clinical Encounters in Training (ReCEnT) cohort study: 4 other regional training providers were controls. In ReCEnT, registrars record detailed data (including prescribing) during 60 consecutive consultations, on 3 occasions. Analysis was at the level of individual problem managed, with the primary outcome factor being prescription of an opioid analgesic and the secondary outcome being opioid initiation. Between 2010 and 2015, 168,528 problems were recorded by 849 registrars. Of these, 71% were recorded by registrars in the nontraining group. Eighty-two percentages were before training. Opioid analgesics were prescribed in 4382 (2.5%, 95% confidence interval [CI]: 2.40-2.63) problems, with 1665 of these (0.97%, 95% CI: 0.91-1.04) representing a new prescription. There was no relationship between the training and total prescribing after training (interaction odds ratio: 1.01; 95% CI: 0.75-1.35; P value 0.96). There was some evidence of a reduction in initial opioid prescriptions in the training group (interaction odds ratio: 0.74; 95% CI: 0.48-1.16; P value 0.19). This brief training package failed to increase overall opioid cessation. The inconsistency of these actual prescribing results with hypothetical prescribing behavior suggests that reducing opioid prescribing in chronic noncancer pain requires more than changing knowledge and attitudes.