Search

Objectives Damage accrual in SSc can be tracked using the Scleroderma Clinical Trials Consortium Damage Index (DI). Our goal was to develop a prediction model for damage accrual in SSc patients with early disease. Methods Using patients with <2 years disease duration from Canada and Australia as a derivation cohort, and from the Netherlands as a validation cohort, we used group-based trajectory modelling (GBTM) to determine 'good' and 'bad' latent damage trajectories. We developed a prediction model from this analysis and applied it to patients from derivation and validation cohorts. We plotted the actual DI trajectories of the patients predicted to be in 'good' or 'bad' groups. Results We found that the actual trajectories of damage accumulation for lcSSc and dcSSc were very different, so we studied each subset separately. GBTM found two distinct trajectories in lcSSc and three in dcSSc. We collapsed the two worse trajectories in the dcSSc into one group and developed a prediction model for inclusion in either 'good' or 'bad' trajectories. The performance of models using only baseline DI and sex was excellent with ROC AUC of 0.9313 for lcSSc and 0.9027 for dcSSc. Using this model, we determined whether patients would fall into 'good' or 'bad' trajectory groups and then plotted their actual trajectories which showed clear differences between the predicted 'good' and 'bad' cases in both derivation and validation cohorts. Conclusions A simple model using only cutaneous subset, baseline DI and sex can predict damage accumulation in early SSc. [ABSTRACT FROM AUTHOR]

Background: Understanding the relationship between different aspects of disadvantage over time and domains of child development will facilitate the formulation of more precise policy responses. We examined the association between exposure to aspects of disadvantage over the childhood period (from 0-9 years) and child development at 10-11 years.Methods: We used data from the nationally representative birth cohort of the Longitudinal Study of Australian Children (n = 4979). Generalized linear models with log-Poisson link were used to estimate the association between previously derived disadvantage trajectories (in each of four lenses of sociodemographic, geographic environments, health conditions and risk factors, and a composite of these) and risk of poor child developmental outcomes. Population-attributable fractions were calculated to quantify the potential benefit of providing all children with optimal conditions for each developmental outcome.Results: Trajectories of disadvantage were associated with developmental outcomes: children in the most disadvantaged composite trajectory had seven times higher risk of poor outcomes on two or more developmental domains, compared with those most advantaged. Trajectories of disadvantage in different lenses were varyingly associated with the child development domains of socio-emotional adjustment, physical functioning and learning competencies. Exposure to the most advantaged trajectory across all lenses could reduce poor developmental outcomes by as much as 70%.Conclusions: Exposure to disadvantage over time is associated with adverse child development outcomes. Developmental outcomes varied with the aspects of disadvantage experienced, highlighting potential targets for more precise policy responses. The findings provide evidence to stimulate advocacy and action to reduce child inequities. [ABSTRACT FROM AUTHOR]

Objectives To investigate associations between leisure-time physical activity (LPA) and injurious falls in older women and explore modification of associations by physical function and frailty. Methods Women born during 1946–51 from the Australian Longitudinal Study on Women's Health, injurious falls (self-reported fall with injury and/or medical attention) and self-reported weekly LPA (duration and type). We undertook cross-sectional and prospective analyses using data from 2016 [ n  = 8,171, mean (SD) age 68 (1)] and 2019 surveys (n  = 7,057). Associations were quantified using directed acyclic graph-informed logistic regression and effect modification examined using product terms. Results Participation in LPA as recommended by World Health Organization (150–300 min/week) was associated with lower odds of injurious falls in cross-sectional (adjusted Odds Ratio (OR) 0.74, 95% CI 0.61–0.90) and prospective analyses (OR 0.75, 95% CI 0.60–0.94). Compared with those who reported no LPA, cross-sectionally, odds of injurious falls were lower in those who reported brisk walking (OR 0.77, 95% CI 0.67–0.89) and vigorous LPA (OR 0.86, 95% CI 0.75–1.00). No significant association was found between different types of LPA and injurious falls prospectively. Only cross-sectionally, physical function limitation and frailty modified the association between LPA and injurious falls, with tendencies for more injurious falls with more activity in those with physical limitation or frailty, and fewer injurious falls with more activity among those without physical function limitation or frailty. Conclusion Participation in recommended levels of LPA was associated with lower odds of injurious falls. Caution is required when promoting general physical activity among people with physical limitation or frailty. [ABSTRACT FROM AUTHOR]

Background Assignment to a community treatment order (CTO) has been associated with reduced mortality risk. In Victoria Australia civil-rights enhancements involving capacity to refuse involuntary treatment have contributed to a 15% reduction between 2010 and 2019 in CTO assignments among first hospitalized patients with Schizophrenia diagnoses. Has this change impacted patient mortality risk? Study Design This study considered mortality-risk between 2010 and 2019 for 3 patient groups with schizophrenia diagnoses: All 4848 hospitalized patients who were assigned to a CTO for the first time in the period; 3988 matched and randomly selected patients, who were first hospitalized in the decade, without CTO assignment; and 1675 never hospitalized or CTO-assigned outpatients. Deaths of Schizophrenic patients in each group were evaluated against expected deaths given standardized mortality ratios for Victoria. Logistic regression was used to evaluate mortality risk for each treatment group while taking account of race, demographics, differential access to initial diagnoses of life-threatening physical illness, mental health service resources, and indicators of social disadvantage. Study Results A total of 78% of the 777 deaths of schizophrenia patients in all 3 groups were premature. The 2 hospitalized groups did not differ in mortality risk. Among Victoria's 2010–2019 outpatients (inclusive of treatment refusers with a recorded service contact), 16.2% had a Schizophrenia diagnosis—up from 0.2% in 2000–2009, the prior decade. Outpatients with Schizophrenia were at 48% greater risk of death than individuals in the hospitalized groups, taking all the afore mentioned risk factors into account. Conclusions Reductions in CTO utilization associated with potential treatment refusals of involuntary community-treatment supervision, seem to have increased mortality risk for this vulnerable population. The line between civil-rights protection and abandonment has been blurred. [ABSTRACT FROM AUTHOR]

Study Question: What is the natural history of reproductive, psychological and oncological features in women with polycystic ovary syndrome (PCOS) in comparison to those without PCOS across the life course?Summary Answer: Existing longitudinal data on changes in reproductive, psychological and oncological features in PCOS are inadequate and conflicting, but the limited evidence suggests that total testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) levels decline more significantly in women with PCOS than in those without PCOS, and the risk of gestational diabetes is higher in pregnant women with PCOS compared to their counterparts without PCOS.What Is Known Already: The progression of reproductive, psychological and oncological features in PCOS remains unclear, which limits prevention and early diagnosis strategies across the lifespan. Understanding the natural history of PCOS is one of the overarching priorities in PCOS research.Study Design, Size, Duration: This is a systematic review of longitudinal cohort studies with a narrative presentation of findings. Databases MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews were searched between 15 January 2020 and 11 February 2021 with no language restrictions. Only studies published from the year 1990 to February 2021 were included.Participants/materials, Setting, Methods: In line with current guidelines for the assessment and management of PCOS, we included studies where participants were females with PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) consensus criteria.Main Results and the Role Of Chance: A total of 21 longitudinal studies including 62 123 participants over four continents reported reproductive, psychological and/or oncological outcomes. Participants were females aged between 15 and 49 years at baseline, with follow-up periods ranging from 4 weeks to 32 years. Consistent evidence based on limited studies suggests that total T and DHEAS levels decline to a greater degree in women with PCOS compared to those without PCOS, and the risk gestational diabetes is higher in women with PCOS than in those without PCOS. Evidence reporting changes over time in the majority of the remaining outcomes was unclear due to conflicting and/or insufficient information.Limitations, Reasons For Caution: There was extreme heterogeneity between studies in terms of study setting, population characteristics, follow-up period, effect measures used and laboratory testing approaches.Wider Implications Of the Findings: Understanding the natural history of PCOS and changes in diagnostic, reproductive, psychological and oncological features of PCOS across the lifespan is still a challenge and the existing literature is both limited and conflicting. It is important that future long-term prospective longitudinal studies are conducted in unselected and well-characterized populations.Study Funding/competing Interest(s): This specific study was not funded. S.K. is supported by scholarships from the Research Training Program of the Commonwealth of Australia and Monash University; H.J.T. is supported by an Australian National Health and Medical Research Council fellowship; and A.E.J. is supported by the Australian National Health and Medical Research Council's Centre for Research Excellence in Women's Health in Reproductive Life. R.A. was employed by the American Society for Reproductive Medicine and is a consultant to Spruce Biosciences and Fortress Biotech. The other authors have no conflicts of interest to declare.Registration Number: Prospero registration number: CRD42020165546. [ABSTRACT FROM AUTHOR]

Background To determine if dried blood spot specimens (DBS) can reliably detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, we compared the SARS-CoV-2 IgG antibody response in paired serum and eluates from DBS specimens. Methods A total of 95 paired DBS and serum samples were collected from 74 participants (aged 1–63 years) as part of a household cohort study in Melbourne, Australia. SARS-CoV-2 IgG antibodies specific for the receptor-binding domain (RBD) and S1 proteins between serum and eluates from DBS specimens were compared using an FDA-approved ELISA method. Results Among the 74 participants, 42% (31/74) were children and the rest were adults. A total of 16 children and 13 adults were SARS-CoV-2 positive by polymerase chain reaction. The IgG seropositivity rate was similar between serum and DBS specimens (18.9% (18/95) versus 16.8% (16/95)), respectively. Similar RBD and S1-specific IgG levels were detected between serum and DBS specimens. Serum IgG levels strongly correlated with DBS IgG levels (r = 0.99, P  < 0.0001) for both SARS-CoV-2 proteins. Furthermore, antibodies remained stable in DBS specimens for >3 months. Conclusions DBS specimens can be reliably used as an alternative to serum samples for SARS-CoV-2 antibody measurement. The use of DBS specimens would facilitate serosurveillance efforts particularly in hard-to-reach populations and inform public health responses including COVID-19 vaccination strategies. [ABSTRACT FROM AUTHOR]

Background: Brief interventions (BIs) delivered in primary care can reduce harmful alcohol consumption. Yet, clinicians do not routinely offer BIs to reduce harmful alcohol use.Objective: We explored the perspectives of clinicians and patients about the use of alcohol BIs during consultations in Australian primary care.Methods: Semi-structured interviews and focus groups (face-to-face and virtual) were undertaken with 34 general practitioners, eight practice nurses and 17 patients. Field notes were made from audio-recordings and themes were identified using a descriptive qualitative approach with the field notes as the point of data analysis.Results: Participants identified barriers within the consultation, practice setting and wider healthcare system plus across the community which reduce the delivery of BIs in primary care including: Australian drinking norms; inconsistent public health messaging around alcohol harm; primary care not recognized as a place to go for help; community stigma towards alcohol use; practice team culture towards preventive health, including systems for recording alcohol histories; limitations of clinical software and current patient resources.Conclusion: Multiple layers of the healthcare system influence the use of BIs in primary care. Identified facilitators for embedding BIs in primary care included: (i) raising community and clinician awareness of the health harms of alcohol, (ii) reinforcing a primary care culture that promotes prevention and, (iii) supportive resources to facilitate discussion about alcohol use and strategies to reduce intake. Alcohol BIs in primary care could be further supported by community public health messages about alcohol use. [ABSTRACT FROM AUTHOR]

Background: Little is known about the long-term health impacts of exposures to landscape fire smoke. We aimed to evaluate the association between exposure to coal mine fire-related particulate matter 2.5 μm or less in diameter (PM2.5) and hospitalisation in the 5 years following the 6-week Hazelwood coal mine fire in Australia in 2014.Methods: We surveyed 2725 residents (mean age: 58.3 years; 54.3% female) from an exposed and a comparison town. Individual PM2.5 exposures during the event were estimated using modelled PM2.5 concentrations related to the coal mine fire and self-reported location data. The individual exposure and survey data were linked with hospitalisation records between January 2009 and February 2019. Recurrent event survival analysis was used to evaluate relationships between PM2.5 exposure and hospitalisation following mine fire, adjusting for important covariates.Results: Each 10-µg/m3 increase in mine fire-related PM2.5 was associated with a 9% increased hazard [hazard ratio (HR) = 1.09; 95% confidence interval (CI): 1.01, 1.17] of respiratory hospitalisation over the next 5 years, with stronger associations observed for females (HR = 1.16; 95% CI: 1.06, 1.27) than males (HR = 0.99; 95% CI: 0.89, 1.11). In particular, increased hazards were observed for hospitalisations for asthma (HR = 1.43; 95% CI: 1.19, 1.73) and chronic obstructive pulmonary disease (HR = 1.14; 95% CI: 1.02, 1.28). No such association was found for hospitalisations for cardiovascular diseases, mental illness, injuries, type 2 diabetes, renal diseases or neoplasms.Conclusions: A 6-week exposure to coal mine fire-related PM2.5 was associated with increased hazard of respiratory hospitalisations over the following 5 years, particularly for females. [ABSTRACT FROM AUTHOR]

Study Question: Do extrinsic factors including lifestyle, psychosocial factors and healthcare professional engagement independently contribute to weight gain in women with and without polycystic ovary syndrome (PCOS)?Summary Answer: Women with PCOS had a higher rate of weight gain than women without PCOS which was most marked in those with unhealthy lifestyles.What Is Known Already: Women with PCOS have a higher prevalence of overweight/obesity and greater weight gain than women without PCOS. The association of lifestyle factors with weight change in PCOS is not known.Study Design, Size, Duration: The study was a population-based observational study with data collected from seven surveys over 19 years (N = 14 127; Survey 1) involving women with and without PCOS.Participants/materials, Setting, Methods: We used data from the 1973-1978 birth cohort of the Australian Longitudinal Study on Women's Health.Main Results and the Role Of Chance: Women with PCOS gained more weight annually (0.26 kg/year; 95% CI 0.12, 0.39; P < 0.0001) and over 19 years (4.62 kg; 95% CI 3.04, 6.21; P < 0.0001) than women without PCOS (adjusted analyses). For all women, there were positive associations between weight gain and energy intake, sitting time and stress; inverse associations with fibre intake and physical activity (PA); and no associations with diet quality, glycaemic index, healthcare utilization, depression or anxiety. There were interactions between lifestyle factors (energy intake P = 0.006, glycaemic index P = 0.025, sitting time P = 0.041 and PA P = 0.021), PCOS status and time such that weight gain varied between women with and without PCOS according to these factors.Limitations, Reasons For Caution: The limitations of this study include the use of self-reported measures such as diet, PA, sitting time, psychological factors and health care utilization.Wider Implications Of the Findings: While women with PCOS are more prone to weight gain, lifestyle factors have a more profound impact on weight gain in women with PCOS than without PCOS. These study findings have implications for understanding the mechanisms of weight gain in women with PCOS. They also highlight the importance of early lifestyle intervention as soon as PCOS is diagnosed to address modifiable extrinsic factors and prevent excess weight gain and worsening of the clinical features of PCOS.Study Funding/competing Interest(s): M.A.A. is funded by the Monash International Tuition Scholarship and Monash Graduate Scholarship and L.J.M. is funded by a National Heart Foundation Future Leader Fellowship. The authors declared no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Do the outcomes and use of ART differ between women with and without endometriosis?Summary Answer: ART use and outcome do not appear to differ for women with and without endometriosis, as long as endometriosis is diagnosed prior to commencing ART.What Is Known Already: Approximately 40% of women with endometriosis have infertility and ART is the recommended treatment option for these women. However, diagnosis of endometriosis can be complex and lengthy, and a delay in diagnosis can reduce the likelihood of achieving a live birth.Study Design, Size, Duration: This retrospective national cohort study used longitudinal self-report data (collected 1996-2018) from women born in 1973-1978 who are participants in the Australian Longitudinal Study on Women's Health (ALSWH). The study also used linked administrative data on Endometriosis (1970-2018), ART (1996-2020) and births (1996-2018).Participants/materials, Setting, Methods: The outcome measures were: age at first ART cycle; use of ART treatments (IVF only; IUI only/and IVF); number of ART cycles (1-3; 4-10; 11-36); and births after first ART (no; yes) (note that births could not be tied to ART).Main Results and the Role Of Chance: One in three (34.7%, n = 459/1322) women using ART had endometriosis, with 65.6% of these diagnosed before first ART and 34.4% after. Adjusted regression analyses showed women with endometriosis diagnosed before first ART were not significantly different to women without endometriosis on any outcome. However, women with endometriosis diagnosed after first ART were more likely to use IUI (adjusted odds ratio (aOR) 2.14, 95% CI 1.48, 3.09) and do more cycles (11-36 cycles: aOR 4.09, 95% CI 2.41, 6.95), and less likely to report a birth (aOR 0.67, 95% CI 0.45, 0.99), compared to women without endometriosis, despite no significant difference in starting age (coefficient = -0.62, 95% CI -1.36, 0.13).Limitations, Reasons For Caution: We did not have information on the severity of endometriosis, or the reasons for using ART, which can influence treatment and outcomes. We were not able to reliably link births with ART treatment. Finally, it is possible that some of the women in our 'no endometriosis' group did have endometriosis and were unaware of it, although prevalence rates match population estimates.Wider Implications Of the Findings: These findings support previous studies that have found no difference in outcome of ART for women with endometriosis, but add the new insight that this is only true if endometriosis is diagnosed prior to commencing ART. A delayed diagnosis can create disadvantage during ART treatment. Early recourse to IVF may be advantageous for pregnancy prospects for women with endometriosis.Study Funding/competing Interest(s): The ALSWH is funded by the Australian Government Department of Health. G.D.M. is supported by an NHMRC Principal Research Fellowship (APP11218449). The authors have no conflicts of interest to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Shared breast cancer follow-up care involving a breast cancer specialist and a general practitioner (GP) has been demonstrated to be effective, yet barriers to participation in this model by women remain. This study explores the responses of women who recently finished active treatment for early breast cancer (EBC) to a proposed model of shared follow-up care to understand the type of information needed to support participation.Methods: Qualitative study based on focus groups with women with EBC in the early stage of follow-up care from across metropolitan, regional and rural settings in Australia. Discussions were transcribed and thematic analysis is undertaken.Results: Four focus groups were conducted, involving 31 women aged between 32 and 78 years. The discussion focused on two topics. In the first topic 'Current experiences of follow-up care', two themes emerged: (i) follow-up as a continuation of active treatment; (ii) GPs involvement in care during active treatment influence attitudes to shared follow-up care. In the second topic area 'Perceptions of shared follow-up care' four themes emerged: (i) a need for evidence regarding model effectiveness; (ii) choice; (iii) concerns regarding capacity and capability of GPs to deliver care and (iv) the need for clear communication between GPs, specialists and women.Conclusions: Women need information regarding the evidence for the effectiveness of shared follow-up care to assure them it does not pose a risk to their health outcomes. Clear descriptions of GP and specialist roles and the opportunity to jointly decide participation is essential for the model to be adopted. [ABSTRACT FROM AUTHOR]

Background: Many studies have reported an inferred causal association of income poverty with physical health among children; but making causal inference is challenging due to multiple potential sources of systematic error. We quantified the short-run effect of changes in household poverty status on children's health (asthma and ear infections) and service use (visits to the doctor and parent-reported hospital admissions), using a national longitudinal study of Australian children, with particular attention to potential residual confounding and selection bias due to study attrition.Methods: We use four modelling approaches differing in their capacity to reduce residual confounding (generalized linear, random effects (RE), hybrid and fixed effects (FE) regression modelling) to model the effect of income poverty (<60% of median income) on health for 10 090 children surveyed every 2nd year since 2004. For each method, we simulate the potential impact of selection bias arising due to attrition related to children's health status.Results: Of the 10 090 children included, 20% were in families in poverty at survey baseline (2004). Across subsequent years, ∼25% experienced intermittent and <2% persistent poverty. No substantial associations between poverty and child physical health and service use were observed in the FE models least prone to residual confounding [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.81-1.10 for wheeze], in contrast to RE models that were positive (consistent with previous studies). Selection bias causing null findings was unlikely.Conclusions: While poverty has deleterious causal effects on children's socio-behavioural and educational outcomes, we find little evidence of a short-run causal effect of poverty on asthma, ear infections and health service use in Australia. [ABSTRACT FROM AUTHOR]

Study Question: What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders?Summary Answer: We identified high confidence disease-causing variants in multiple genes previously associated with severe sperm motility disorders in 10 out of 21 patients (48%) and variants in novel candidate genes in seven additional patients (33%).What Is Known Already: Severe sperm motility disorders are a form of male infertility characterised by immotile sperm often in combination with a spectrum of structural abnormalities of the sperm flagellum that do not affect viability. Currently, depending on the clinical sub-categorisation, up to 50% of causality in patients with severe sperm motility disorders can be explained by pathogenic variants in at least 22 genes.Study Design, Size, Duration: We performed exome sequencing in 21 patients with severe sperm motility disorders from two different clinics.Participants/materials, Setting, Method: Two groups of infertile men, one from Argentina (n = 9) and one from Australia (n = 12), with clinically defined severe sperm motility disorders (motility <5%) and normal morphology values of 0-4%, were included. All patients in the Argentine cohort were diagnosed with DFS-MMAF, based on light and transmission electron microscopy. Sperm ultrastructural information was not available for the Australian cohort. Exome sequencing was performed in all 21 patients and variants with an allele frequency of <1% in the gnomAD population were prioritised and interpreted.Main Results and Role Of Chance: In 10 of 21 patients (48%), we identified pathogenic variants in known sperm assembly genes: CFAP43 (3 patients); CFAP44 (2 patients), CFAP58 (1 patient), QRICH2 (2 patients), DNAH1 (1 patient) and DNAH6 (1 patient). The diagnostic rate did not differ markedly between the Argentinian and the Australian cohort (55% and 42%, respectively). Furthermore, we identified patients with variants in the novel human candidate sperm motility genes: DNAH12, DRC1, MDC1, PACRG, SSPL2C and TPTE2. One patient presented with variants in four candidate genes and it remains unclear which variants were responsible for the severe sperm motility defect in this patient.Large Scale Data: N/A.Limitations, Reasons For Caution: In this study, we described patients with either a homozygous or two heterozygous candidate pathogenic variants in genes linked to sperm motility disorders. Due to unavailability of parental DNA, we have not assessed the frequency of de novo or maternally inherited dominant variants and could not determine the parental origin of the mutations to establish in all cases that the mutations are present on both alleles.Wider Implications Of the Findings: Our results confirm the likely causal role of variants in six known genes for sperm motility and we demonstrate that exome sequencing is an effective method to diagnose patients with severe sperm motility disorders (10/21 diagnosed; 48%). Furthermore, our analysis revealed six novel candidate genes for severe sperm motility disorders. Genome-wide sequencing of additional patient cohorts and re-analysis of exome data of currently unsolved cases may reveal additional variants in these novel candidate genes.Study Funding/competing Interest(s): This project was supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., J.A.V. and R.I.M.L., The Netherlands Organisation for Scientific Research (918-15-667) to J.A.V., the Royal Society and Wolfson Foundation (WM160091) to J.A.V., as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. and Grants from the National Research Council of Argentina (PIP 0900 and 4584) and ANPCyT (PICT 9591) to H.E.C. and a UUKi Rutherford Fund Fellowship awarded to B.J.H. [ABSTRACT FROM AUTHOR]

Study Question: Is cord blood DNA methylation associated with having been conceived by medically assisted reproduction?Summary Answer: This study does not provide strong evidence of an association of conception by medically assisted reproduction with variation in infant blood cell DNA methylation.What Is Known Already: Medically assisted reproduction consists of procedures used to help infertile/subfertile couples conceive, including ART. Due to its importance in gene regulation during early development programming, DNA methylation and its perturbations associated with medically assisted reproduction could reveal new insights into the biological effects of assisted reproductive technologies and potential adverse offspring outcomes.Study Design, Size, Duration: We investigated the association of DNA methylation and medically assisted reproduction using a case-control study design (N = 205 medically assisted reproduction cases and N = 2439 naturally conceived controls in discovery cohorts; N = 149 ART cases and N = 58 non-ART controls in replication cohort).Participants/materials, Settings, Methods: We assessed the association between medically assisted reproduction and DNA methylation at birth in cord blood (205 medically assisted conceptions and 2439 naturally conceived controls) at >450 000 CpG sites across the genome in two sub-samples of the UK Avon Longitudinal Study of Parents and Children (ALSPAC) and two sub-samples of the Norwegian Mother, Father and Child Cohort Study (MoBa) by meta-analysis. We explored replication of findings in the Australian Clinical review of the Health of adults conceived following Assisted Reproductive Technologies (CHART) study (N = 149 ART conceptions and N = 58 controls).Main Results and the Role Of Chance: The ALSPAC and MoBa meta-analysis revealed evidence of association between conception by medically assisted reproduction and DNA methylation (false-discovery-rate-corrected P-value < 0.05) at five CpG sites which are annotated to two genes (percentage difference in methylation per CpG, cg24051276: Beta = 0.23 (95% CI 0.15,0.31); cg00012522: Beta = 0.47 (95% CI 0.31, 0.63); cg17855264: Beta = 0.31 (95% CI 0.20, 0.43); cg17132421: Beta = 0.30 (95% CI 0.18, 0.42); cg18529845: Beta = 0.41 (95% CI 0.25, 0.57)). Methylation at three of these sites has been previously linked to cancer, aging, HIV infection and neurological diseases. None of these associations replicated in the CHART cohort. There was evidence of a functional role of medically assisted reproduction-induced hypermethylation at CpG sites located within regulatory regions as shown by putative transcription factor binding and chromatin remodelling.Limitations, Reasons For Cautions: While insufficient power is likely, heterogeneity in types of medically assisted reproduction procedures and between populations may also contribute. Larger studies might identify replicable variation in DNA methylation at birth due to medically assisted reproduction.Wider Implications Of the Findings: Newborns conceived with medically assisted procedures present with divergent DNA methylation in cord blood white cells. If these associations are true and causal, they might have long-term consequences for offspring health.Study Funding/competing Interests(s): This study has been supported by the US National Institute of Health (R01 DK10324), the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no. 669545, European Union's Horizon 2020 research and innovation programme under Grant agreement no. 733206 (LifeCycle) and the NIHR Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Methylation data in the ALSPAC cohort were generated as part of the UK BBSRC funded (BB/I025751/1 and BB/I025263/1) Accessible Resource for Integrated Epigenomic Studies (ARIES, http://www.ariesepigenomics.org.uk). D.C., J.J., C.L.R. D.A.L and H.R.E. work in a Unit that is supported by the University of Bristol and the UK Medical Research Council (Grant nos. MC_UU_00011/1, MC_UU_00011/5 and MC_UU_00011/6). B.N. is supported by an NHMRC (Australia) Investigator Grant (1173314). ALSPAC GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (Contract no. N01-ES-75558), NIH/NINDS (Grant nos. (i) UO1 NS 047537-01 and (ii) UO1 NS 047537-06A1). For this work, MoBa 1 and 2 were supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and the Norwegian Research Council/BIOBANK (Grant no. 221097). This work was partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, Project no. 262700.D.A.L. has received support from national and international government and charity funders, as well as from Roche Diagnostics and Medtronic for research unrelated to this study. The other authors declare no conflicts of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Are reproductive, metabolic or psychological health profiles of women with clinically diagnosed polycystic ovary syndrome (PCOS) different from those with undiagnosed PCOS?Summary Answer: Obtaining a clinical diagnosis of PCOS is strongly linked to the experience of fertility problems, but not clinical depression or poor metabolic health, although these were highly prevalent in women with PCOS irrespective of when they were diagnosed.What Is Known Already: PCOS is an endocrine disorder that is relative common, but heterogeneous in presentation. This may impact on the pathways to diagnosis and timely treatment.Study Design, Size, Duration: A cross-sectional analysis of a community-based cohort of 974 women, established retrospectively when women were around 30 years of age.Participants/materials, Setting, Methods: In this cohort of women born in Adelaide, South Australia, half of women who met the Rotterdam criteria for PCOS were previously undiagnosed. We compared women with prior clinical diagnosis of PCOS, those diagnosed through participation in this research, and the remainder in the cohort. Sociodemographic characteristics, reproductive, metabolic and psychological health, including medical conditions and medications were considered. Logistic regression was undertaken to identify independent predictors of prior clinical diagnosis.Main Results and the Role Of Chance: There were 56 women with a prior clinical diagnosis of PCOS (5.7%) and a further 64 (6.6%) were undiagnosed until study entry. The great majority of women with a prior diagnosis of PCOS reported having had problems with periods (95%) and excess body hair (63%). Corresponding proportions for women undiagnosed until study participation were slightly lower (81% and 45%, respectively). Although the proportion of women attempting or achieving pregnancy was similar across all groups, those with a prior diagnosis of PCOS were four times more likely to have reported difficulties becoming pregnant than those undiagnosed (odds ratio = 4.05, 95% CI 1.74-9.45) and frequently sought medical assistance. Metabolic problems were higher in both PCOS groups compared to women without PCOS. In both PCOS groups, the prevalence of clinical depression was 50% higher than in those with no PCOS (P = 0.021).Limitations, Reasons For Caution: The number of women who were diagnosed with PCOS both prior to and during the study limited statistical power available to detect modest differences between the PCOS groups. Some women in the group classified as not having PCOS may have remained undiagnosed, but any bias from this source would contribute to more conservative findings.Wider Implications Of the Findings: Findings reinforce the need for early detection of PCOS symptoms from adolescence, ensuring timely diagnosis and appropriate health care. The high prevalence of depression among clinically diagnosed and undiagnosed women with PCOS suggests this is a feature of the condition and supports recent recommendations in the international PCOS guidelines to screen all women with PCOS for depression and anxiety.Study Funding/competing Interest(s): This work was supported by a project grant (2017) from the National Health and Medical Research Council of Australia (NHMRC) Centre for Research Excellence in Polycystic Ovary Syndrome (Grant ID APP1078444). R.C.F. and J.C.A. were supported by Robinson Research Institute Lloyd Cox Career Development Fellowships (2018). Establishment of the cohort was funded by an NHMRC Strategic Award No. 465455, a Career Development Award in Population Health (No. 349548) and the Australian Research Council (Future Fellowship FT100101018) awarded to M.J.D. All authors declared no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Do the epigenome-wide DNA methylation profiles of adolescents born from ART differ from the epigenome of naturally conceived counterparts?Summary Answer: No significant differences in the DNA methylation profiles of adolescents born from ART [IVF or ICSI] were observed when compared to their naturally conceived, similar aged counterparts.What Is Known Already: Short-term and longer-term studies have investigated the general health outcomes of children born from IVF treatment, albeit without common agreement as to the cause and underlying mechanisms of these adverse health findings. Growing evidence suggests that the reported adverse health outcomes in IVF-born offspring might have underlying epigenetic mechanisms.Study Design, Size, Duration: The Growing Up Healthy Study (GUHS) is a prospective study that recruited 303 adolescents and young adults, conceived through ART, to compare various long-term health outcomes and DNA methylation profiles with similar aged counterparts from Generation 2 from the Raine Study. GUHS assessments were conducted between 2013 and 2017. The effect of ART on DNA methylation levels of 231 adolescents mean age 15.96 ± 1.59 years (52.8% male) was compared to 1188 naturally conceived counterparts, 17.25 ± 0.58 years (50.9% male) from the Raine Study.Participants/materials, Setting, Methods: DNA methylation profiles from a subset of 231 adolescents (13-19.9 years) from the GUHS, generated using the Infinium Methylation Epic Bead Chip (EPIC) array were compared to 1188 profiles from the Raine Study previously measured using the Illumina 450K array. We conducted epigenome-wide association approach (EWAS) and tested for an association between the cohorts applying Firth's bias reduced logistic regression against the outcome of ART versus naturally conceived offspring. Additionally, within the GUHS cohort, we investigated differences in methylation status in fresh versus frozen embryo transfers, cause of infertility as well as IVF versus ICSI conceived offspring. Following the EWAS analysis we investigated nominally significant probes using Gene Set Enrichment Analysis (GSEA) to identify enriched biological pathways. Finally, within GUHS we compared four estimates (Horvath, Hanuum, PhenoAge [Levine], and skin Horvath) of epigenetic age and their correlation with chronological age.Main Results and the Role Of Chance: Between the two cohorts, we did not identify any DNA methylation probes that reached a Bonferroni corrected P-value < 1.24E-0.7. When comparing IVF versus ICSI conceived adolescents within the GUHS cohort, after adjustment for participant age, sex, maternal smoking, multiple births, and batch effect, three methylation probes (cg15016734, cg26744878 and cg20233073) reached a Bonferroni correction of 6.31E-08. After correcting for cell count heterogeneity, two of the aforementioned probes remained significant and an additional two probes (cg 0331628 and cg 20235051) were identified. A general trend towards hypomethylation in the ICSI offspring was observed. All four measures of epigenetic age were highly correlated with chronological age and showed no evidence of accelerated epigenetic aging within their whole blood.Limitations, Reasons For Caution: The small sample size coupled with the use of whole blood, where epigenetic differences may occur in other tissue. This was corrected by the utilized statistical method that accounts for imbalanced sample size between groups and adjusting for cell count heterogeneity. Only a small portion of the methylome was analysed and rare individual differences may be missed.Wider Implications Of the Findings: Our findings provide further reassurance that the effects of the ART manipulations occurring during early embryogenesis, existing in the neonatal period are indeed of a transient nature and do not persist into adolescence. However, we have not excluded that alternative epigenetic mechanisms may be at play.Study Funding/competing Interest(s): This project was supported by NHMRC project Grant no. 1042269 and R.J.H. received funding support from Ferring Pharmaceuticals Pty Ltd. R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from Merck Sharp & Dohme Corp.- Australia, Merck-Serono Australia Pty Ltd and Ferring Pharmaceuticals Pty Ltd. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director of PIVET Medical Centre, Perth, Western Australia. The remaining authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: Despite generally high smoking prevalences, stemming from colonization, the relationship of smoking to mortality has not been quantified reliably in an Indigenous population. We investigate smoking and mortality among Aboriginal and Torres Strait Islander adults in Australia, where current adult daily smoking prevalence is 40.2%.Methods: A prospective study of 1388 cardiovascular disease- and cancer-free Aboriginal adults aged ≥45 years, of the 267 153 45 and Up Study participants randomly sampled from the New South Wales general population over 2006-09. Questionnaire and mortality data were linked (through the Centre for Health Record Linkage) to mid-2019. Adjusted hazard ratios (called relative risks, RRs) for all-cause mortality-among current- and past- versus never-smokers-were estimated overall, by smoking intensity and by age at cessation. Smoking-attributable fractions and associated deaths were estimated.Results: Over 14 586 person-years' follow-up (median 10.6 years), 162 deaths accrued. Mortality RRs [95% confidence interval (CI)] were 3.90 (2.52-6.04) for current- and 1.95 (1.32-2.90) for past- versus never-smokers, with age heterogeneity. RRs increased with smoking intensity, to 4.29 (2.15-8.57) in current-smokers of ≥25 cigarettes/day. Compared with never-smokers, RRs were 1.48 (0.85-2.57) for those quitting at <45 years of age and 2.21 (1.29-3.80) at 45-54 years. Never-smokers lived an average >10 years longer than current-smokers. Around half of deaths among adults aged ≥45 years were attributable to smoking, exceeding 10 000 deaths in the past decade.Conclusions: In this population, >80% of never-smokers would survive to 75 years, versus ∼40% of current-smokers. Quitting at all ages examined had substantial benefits versus continuing smoking; those quitting before age 45 years had mortality risks similar to never-smokers. Smoking causes half of deaths in older Aboriginal and Torres Strait Islander adults; Indigenous tobacco control must receive increased priority. [ABSTRACT FROM AUTHOR]

Study Question: Are physical activity (PA) and body mass index (BMI) associated with irregular periods and heavy menstrual bleeding (HMB) in Australian women?Summary Answer: Overweight and obese women have higher odds of both irregular periods and HMB than underweight/normal-weight women, but high levels of PA reduce the odds of HMB.What Is Known Already: Most studies on relationships between PA and menstrual problems have focused on female athletes, but there have been few population-based studies.Study Design, Size, Duration: Prospective cohort study, 10618 participants in the Australian Longitudinal Study of Women's Health (ALSWH) who completed mailed surveys in 1996, with follow-ups in 2000, 2003, 2006, 2009, 2012, and 2015.Participants/materials, Setting, Methods: Participants were aged 22 to 27 in 2000. They were asked to report their PA levels and the frequency of irregular periods and HMB in each survey. BMI was calculated at every survey from self-reported weight and height. Generalised estimating equation population-averaged model analyses were conducted to calculate odds ratios (OR) and 95% confidence intervals (95% CIs).Main Results and the Role Of Chance: At age 22 to 27 years, the prevalence of irregular periods was 19.4%. This remained stable over 15 years. There were no associations between PA and irregular periods. Overweight and obese women had higher odds of irregular periods [overweight: OR 1.08, (95% CI 1.00-1.17); obese: OR 1.29, (95%CI 1.18-1.41)] than women who were underweight/normal weight.The prevalence of HMB at age 22-27 years was 15.9%; this doubled over 15 years. Women who were highly active had 10% lower odds of HMB than women who reported no PA [OR 0.90, (95%CI 0.82-0.98)]. Overweight and obese women had higher odds of HMB [overweight: OR 1.15, (95%CI 1.07-1.23); obese: OR 1.37, (95%CI 1.26-1.49)] than women who were underweight/normal weight. Among obese women, high levels of PA were associated with 19% [OR 0.81, (95%CI 0.68-0.97)] reduction in the odds of HMB.Limitations, Reasons For Caution: Data collected in the ALSWH are self-reported, which may be subject to recall bias. Reverse causation, due to menstrual problems impacting PA, is possible although sensitivity analyses suggest this is unlikely to have affected the results. Other conditions, e.g., polycystic ovary syndrome, for which no or incomplete data were available, could have affected the results.Wider Implications Of the Findings: Intervention studies are needed to assess the effect of increasing PA in women with HMB, but these preliminary findings suggest that promoting PA could be an affordable and feasible strategy for reducing HMB in young adult women.Study Funding/competing Interest(s): The ALSWH is funded by the Australian Government. Funding for these analyses was provided by a University of Queensland (UQ) International Postgraduate Research Scholarship and a UQ International Development Fellowship. The authors declare no conflicts of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Serum 25 hydroxyvitamin D [25(OH)D] levels of pregnant women have been linked to various health outcomes in their offspring. Satellite-derived ultraviolet radiation (UVR) data have been used as a proxy for 25(OH)D levels, as individual-level cohort studies are time-consuming, costly and only feasible for common outcomes.Methods: Data on 25(OH)D levels from a public laboratory database were linked to data from the Western Australian Midwives' Notification System and daily erythemal UVR dose from NASA satellites. Regression analysis was used to identify the time period prior to venesection where daily UVR dose best predicted 25(OH)D levels. A predictive model was used to validate the use of daily UVR dose as a proxy for personal sun exposure during pregnancy.Results: Data from 19 173 pregnancies in women aged 18-43 years in Western Australia were included. The daily UVR dose averaged over the 90 days before venesection was the strongest UVR predictor of 25(OH)D level (a 5% increase per 1000 J m-2; equal to 3.3 nmol L-1 at the median of 66 nmol L-1). Ethnicity was the strongest predictor of 25(OH)D levels (21% lower in non-Caucasian vs Caucasian: equal to 7.2 nmol L-1 difference). Other significant predictors were gestation, age, year, parity, socio-economic status, remoteness, medical conditions and season.Conclusion: NASA-derived erythemal UVR dose in the 90 days prior to venesection is a significant predictor of 25(OH)D levels in pregnant women. Linked administrative data can be used to investigate associations between UVR during pregnancy and health outcomes in offspring. [ABSTRACT FROM AUTHOR]

Objective: This study used retrospective linked population data to investigate the impact of early childhood cancer on developmental outcomes.Methods: Children aged <9 years with a recorded malignant neoplasm were identified in the South Australian Cancer Registry. They were then linked to developmental data recorded in the Australian Early Development Census (AEDC) for the 2009, 2012, and 2015 data collection periods; and assigned five matched controls from the same AEDC year.Results: Between 2000 and 2015, 43 children had a malignant cancer diagnosis and also participated in the AEDC. Compared to controls, childhood cancer survivors exhibited greater developmental vulnerability in their physical health and wellbeing. Between survivors and controls, no significant developmental differences were observed in social, emotional, language and cognitive, and communication and general knowledge domains. Rural or remote location had a significant positive effect on developmental outcomes for childhood cancer survivors relative to controls, suggesting this was a protective factor in terms of physical health and wellbeing, social competence, communication, and general knowledge. Among all children, socioeconomic advantage was linked to better developmental outcomes on all domains except physical health and wellbeing.Conclusion: Following an early cancer diagnosis, children may require targeted care to support their physical health and wellbeing. Geographic variation in developmental outcomes indicates remoteness was a protective factor and requires further investigation. This study highlights the feasibility of using administrative whole-population data to investigate cancer outcomes. [ABSTRACT FROM AUTHOR]

Objective: To explore differences in position emission tomography-computed tomography (PET-CT) service provision internationally to further understand the impact variation may have upon cancer services. To identify areas of further exploration for researchers and policymakers to optimize PET-CT services and improve the quality of cancer services.Design: Comparative analysis using data based on pre-defined PET-CT service metrics from PET-CT stakeholders across seven countries. This was further informed via document analysis of clinical indication guidance and expert consensus through round-table discussions of relevant PET-CT stakeholders. Descriptive comparative analyses were produced on use, capacity and indication guidance for PET-CT services between jurisdictions.Setting: PET-CT services across 21 jurisdictions in seven countries (Australia, Denmark, Canada, Ireland, New Zealand, Norway and the UK).Participants: None.Intervention(s): None.Main Outcome Measure(s): None.Results: PET-CT service provision has grown over the period 2006-2017, but scale of increase in capacity and demand is variable. Clinical indication guidance varied across countries, particularly for small-cell lung cancer staging and the specific acknowledgement of gastric cancer within oesophagogastric cancers. There is limited and inconsistent data capture, coding, accessibility and availability of PET-CT activity across countries studied.Conclusions: Variation in PET-CT scanner quantity, acquisition over time and guidance upon use exists internationally. There is a lack of routinely captured and accessible PET-CT data across the International Cancer Benchmarking Partnership countries due to inconsistent data definitions, data linkage issues, uncertain coverage of data and lack of specific coding. This is a barrier in improving the quality of PET-CT services globally. There needs to be greater, richer data capture of diagnostic and staging tools to facilitate learning of best practice and optimize cancer services. [ABSTRACT FROM AUTHOR]

Background: A farm upbringing has been associated with lower risk of asthma and methylation of asthma-related genes. As such, a farm upbringing has the potential to transfer asthma risk across generations, but this has never been investigated. We aimed to study the generational effects from a parental farm upbringing on offspring asthma.Methods: Our study involved three generations: 5759 participants from the European Community Respiratory Health Survey (ECRHS) study (born 1945-1971, denoted G1), their 9991 parents (G0) and their 8260 offspring (G2) participating in RHINESSA (Respiratory Health In Northern Europe, Spain and Australia). Questionnaire data were collected on G0 and G1 from G1 in 2010 and on G2 from themselves in 2013. The parental/grandparental place of upbringing was categorized: (i) both parents from farm; (ii) mother from farm, father from village/city; (iii) father from farm, mother from village/city; (iv) both parents from village or one parent from village and one from city; (v) both parents from city (reference group). Grandparental upbringing was equivalently categorized. Offspring asthma was self-reported and data were analysed using Cox-regression models with G2 age as the time scale.Results: A parental farm upbringing was not associated with offspring asthma when compared with city upbringing [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.74-1.69]. Findings remained similar when stratified by offspring upbringing and asthma phenotypes. Quantitative bias analyses showed similar estimates for alternative data sources. A grandparental farm upbringing was not associated with offspring asthma in either the maternal (HR 1.05, 95% CI 0.67-1.65) or paternal line (HR 1.02, 95% CI 0.62-1.68).Conclusions: This multigenerational analysis suggests no evidence of an association between parental/grandparental farm upbringing and offspring asthma. [ABSTRACT FROM AUTHOR]

Study Question: Is one cycle of IVM non-inferior to one cycle of conventional in IVF with respect to live birth rates in women with high antral follicle counts (AFCs)?Summary Answer: We could not demonstrate non-inferiority of IVM compared with IVF.What Is Known Already: IVF with ovarian hyperstimulation has limitations in some subgroups of women at high risk of ovarian stimulation, such as those with polycystic ovary syndrome. IVM is an alternative ART for these women. IVM may be a feasible alternative to IVF in women with a high AFC, but there is a lack of data from randomized clinical trials comparing IVM with IVF in women at high risk of ovarian hyperstimulation syndrome.Study Design, Size, Duration: This single-center, randomized, controlled non-inferiority trial was conducted at an academic infertility center in Vietnam from January 2018 to April 2019.Participants/materials, Setting, Methods: In total, 546 women with an indication for ART and a high AFC (≥24 follicles in both ovaries) were randomized to the IVM (n = 273) group or the IVF (n = 273) group; each underwent one cycle of IVM with a prematuration step versus one cycle of IVF using a standard gonadotropin-releasing hormone antagonist protocol with gonadotropin-releasing hormone agonist triggering. The primary endpoint was live birth rate after the first embryo transfer. The non-inferiority margin for IVM versus IVF was -10%.Main Results and the Role Of Chance: Live birth after the first embryo transfer occurred in 96 women (35.2%) in the IVM group and 118 women (43.2%) in the IVF group (absolute risk difference -8.1%; 95% confidence interval (CI) -16.6%, 0.5%). Cumulative ongoing pregnancy rates at 12 months after randomization were 44.0% in the IVM group and 62.6% in the IVF group (absolute risk difference -18.7%; 95% CI -27.3%, -10.1%). Ovarian hyperstimulation syndrome did not occur in the IVM group, versus two cases in the IVF group. There were no statistically significant differences between the IVM and IVF groups with respect to the occurrence of pregnancy complications, obstetric and perinatal complications, preterm delivery, birth weight and neonatal complications.Limitations, Reasons For Caution: The main limitation of the study was its open-label design. In addition, the findings are only applicable to IVM conducted using the prematuration step protocol used in this study. Finally, the single ethnicity population limits the external generalizability of the findings.Wider Implications Of the Findings: Our randomized clinical trial compares live birth rates after IVM and IVF. Although IVM is a viable and safe alternative to IVF that may be suitable for some women seeking a mild ART approach, the current study findings approach inferiority for IVM compared with IVF when cumulative outcomes are considered. Future research should incorporate multiple cycles of IVM in the study design to estimate cumulative fertility outcomes and better inform clinical decision-making.Study Funding/competing Interest(s): This work was partly supported by Ferring grant number 000323 and funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) and by the Fund for Research Flanders (FWO). LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; RJN has received conference and scientific board fees from Ferring, is a minor shareholder in an IVF company, and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant; RBG reports grants and fellowships from the NHMRC of Australia; JS reports lecture fees from Ferring Pharmaceuticals, Biomérieux, Besins Female Healthcare and Merck, grants from Fund for Research Flanders (FWO), and is co-inventor on granted patents on CAPA-IVM methodology in the US (US10392601B2) and Europe (EP3234112B1); TDP, VQD, VNAH, NHG, AHL, THP and RW have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.Trial Registration Number: NCT03405701 (www.clinicaltrials.gov).Trial Registration Date: 16 January 2018.Date Of First Patent’s Enrolment: 25 January 2018. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional studies suggest that more green space may lower the odds of prevalent diabetes, hypertension and cardiovascular diseases (CVD) in cities. We assess if these results are replicable for tree canopy exposure and then extend the study longitudinally to examine incident cardiometabolic outcomes.Methods: The study was set in the Australian cities of Sydney, Wollongong and Newcastle. Total green space and tree canopy as percentages of landcover within 1.6 km (1 mile) from home were linked to a residentially stable sample of 46 786 participants in the Sax Institute's 45 and Up Study (baseline 2006-09; follow-up 2012-15). Separate multilevel models were used to investigate whether the odds of prevalent and incident doctor-diagnosed diabetes, hypertension and CVD were associated with total green space and tree canopy provision, adjusting for age, sex, income, education, employment and couple status.Results: Lower odds of prevalent diabetes were observed with 1% increases in total green space [odds ratio (OR) 0.993, 95% confidence interval (CI) 0.988 to 0.998] and tree canopy (0.984, 0.978 to 0.989). Lower odds of prevalent CVD were found with a 1% increase in tree canopy only (0.996, 0.993 to 0.999). Lower odds of incident diabetes (0.988, 0.981 to 0.994), hypertension (0.993, 0.989 to 0.997) and CVD (0.993, 0.988 to 0.998) were associated with a 1% increase in tree canopy, but not total green space. At ≥30% compared with 0-9% tree canopy, there were lower odds of incident diabetes (0.687, 0.547 to 0.855), hypertension (0.828, 0.719 to 0.952) and CVD (0.782, 0.652 to 0.935). However, ≥30% compared with 0-4% total green space was associated with lower odds of prevalent diabetes only (0.695, 0.512 to 0.962).Conclusions: Restoring local tree canopy in neighbourhoods may help to prevent the incidence of cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Background: The ways children spend their time is one of the most valuable inputs for healthy child development. It is unknown which time investment yields the greatest return for children's language and behavioural outcomes at school entry.Methods: We used data from the first three waves (2004, 2006, 2008) of the Longitudinal Study of Australian Children (n = 4253). At every wave, parents completed 24-h time-use diaries on one randomly selected week and one weekend day. The amount of time children spent on 11 activities at ages 0-1, 2-3 and 4-5 years was analysed. Receptive vocabulary was assessed using the Peabody Picture Vocabulary Test, and externalizing behaviours were measured by the Strengths and Difficulties Questionnaire, completed by parents and teachers at 4-5 years. To identify which time investment in the first 5 years of life mattered most for children's outcomes, a new production function was developed. This production function was estimated using a log-log linear regression model.Results: Relative to other time investments, time spent on educational activities at 2-3 years of age was the most important time investment for receptive vocabulary and behavioural outcomes at school entry. After adjusting for confounding, every 1 h invested in educational activities at 2-3 years was associated with a 0.95% [95% CI (confidence interval): 0.62, 1.28] increase in receptive vocabulary, and a -5.72% (95% CI: -7.71, -3.73) and -9.23% (95% CI: -12.26, -6.20) reduction in parent- and teacher-reported externalizing problem behaviours. Time invested in play was also important to both receptive vocabulary and behaviour. One hour invested in play at 2-3 and 4-5 years was associated with a 0.68% (95% CI: 0.38, 0.98) and 0.71% (95% CI: 0.39, 1.03) increase in children's receptive vocabulary at school entry. In addition, time invested in play at 2-3 and 4-5 years was associated with reduced problem behaviours at school entry. In contrast, screen time at all ages was associated with poorer parent- and teacher-reported externalizing problem behaviours.Conclusions: These results suggest that time invested in educational activities at 2-3 years of age yield the greatest return for children's receptive vocabulary and behaviour at school entry. [ABSTRACT FROM AUTHOR]

Study Question: Do physical activity (PA), sitting time (ST) and body mass index (BMI) affect fertility over a 15-year period in Australian women?Summary Answer: Moderate and high levels of PA confer advantages for fertility in women with normal BMI, but increased risk of infertility was observed in obese women.What Is Known Already: Higher BMI is positively associated with higher rates of problems with fertility, but the effects of physical activity and sitting time on fertility are less well understood.Study Design, Size, Duration: Participants in The Australian Longitudinal Study of Women's Health (ALSWH) completed mailed surveys in 2000, with follow-ups in 2003, 2006, 2009, 2012 and 2015 (N = 6130).Participants/materials, Setting, Methods: Participants were aged 22 to 27 in 2000. They were asked to report their physical activity levels, sitting time and fertility problems in each survey from 2000 to 2015. BMI was calculated from self-reported weight and height. Cumulative incidence of fertility problems was calculated from 2000 to 2015 and hazard ratios (HR) and 95% CIs were calculated using survival analysis.Main Results and the Role Of Chance: From 2000 to 2015, the cumulative incidence of fertility problems was 15.4% (95% CI: 14.5-16.4). High levels of PA were associated with reduced risk of problems with fertility [HR 0.82 (95% CI: 0.69-0.98)], and higher BMI was positively associated with fertility problems [overweight: HR 1.18, (95% CI 0.99-1.39); obese: HR 1.36, (95% CI 1.14-1.63)]. In survival analyses, incidence rates were highest in every survey interval in women who reported low PA levels and in women who were obese. Overall, ST was not associated with fertility problems. In stratified models, high levels of PA attenuated the risk of problems with fertility in women who were in the normal BMI category [HR 0.64, (95% CI 0.49-0.82)].Limitations, Reasons For Caution: The ALSWH relies on self-reported data, which may be subject to recall bias.Wider Implications Of the Findings: The study provides estimates of problems with fertility in a cohort of young adult Australian women, and the results indicate that these are inversely associated with physical activity levels and positively associated with BMI. However, the high infertility risk in obese women was not attenuated by high levels of PA. The protective effects of PA were only observed in women with normal BMI. As rates of developing problems with fertility were highest in every survey interval among women who reported low levels of physical activity and in women who were obese, these findings suggest that improving physical activity levels could be an affordable strategy to reduce problems with fertility in women who are trying to conceive. These findings should be considered by clinical and public health practitioners.Study Funding/competing Interest(s): The ALSWH is funded by the Australian Government. Funding for these analyses was provided by a University of Queensland (UQ) International Postgraduate Research Scholarship and a UQ International Development Fellowship. The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: This study assessed the association between coal-mine-fire-related fine particulate matter (PM2.5) and medical-service utilization, following a 6-week coal-mine fire in Australia, in 2014. Areas in the immediate vicinity of the mine experienced hourly mine-fire-related PM2.5 concentrations of up to 3700 μg/m3.Methods: Data on medical-service utilization were collected from the Medicare Benefits Schedule-a national database of payment for medical services. PM2.5 concentrations were modelled using atmospheric chemical transport modelling. Quasi-Poisson interrupted distributed lag time-series analysis examined the association between daily mine-fire-related PM2.5 concentrations and medical-service utilization, including General Practitioner (GP) consultations and respiratory, cardiovascular and mental health services. Confounders included seasonality, long-term trend, day of the week, maximum daily temperature and public holidays. Gender and age stratification were conducted.Results: A 10-μg/m3 increase in PM2.5 was associated with an increased relative risk of service usage for all long and short GP consultations [11% (95% confidence interval: 7 to 15%)] and respiratory services [22% (4 to 43%)] in both men and women. Sex stratification found an increased relative risk in mental health consultations in men [32% (2 to 72%)] but not women. No associations were found for cardiovascular services in men or women.Conclusions: Coal-mine-fire-related PM2.5 exposure was associated with increased use of medical services for GP consultations and respiratory services in men and women and mental health consultations in men. These findings can inform the development of future public-health-policy responses in the event of major air-pollution episodes. [ABSTRACT FROM AUTHOR]

Study Question: Do diet, physical activity and contraceptive use change after receiving a diagnosis of polycystic ovary syndrome (PCOS)?Summary Answer: Using longitudinal data 12 months apart, young women newly diagnosed with PCOS were more likely to stop using contraception but did not change their physical activity or vegetable intake.What Is Known Already: Diagnostic criteria for PCOS have widened to capture more women, despite limited evidence of the benefits and harms. Possible benefits of a PCOS diagnosis are that it may help women with family planning and motivate them to implement healthy lifestyle changes to reduce the reproductive, metabolic and cardiovascular risks associated with PCOS. However, there are no empirical studies investigating how women respond to a diagnosis of PCOS with respect to their health behaviour, and longitudinal population-based studies are lacking.Study Design, Size, Duration: This is a longitudinal analysis of two waves of data collected 12 months apart from the cohort born 1989-1995 in the Australian Longitudinal Survey on Women's Health, a population-based cohort study. Women in this cohort were first surveyed in 2012-2013, aged 18-23 years.Participants/materials, Setting, Methods: Women who responded to the 2014 survey (aged 19-24, n = 11 344) and 2015 survey (aged 20-25, n = 8961) were included. Using logistic regression, multinomial logistic regression and linear regression, change in vegetable intake, physical activity and contraceptive use were compared for women newly diagnosed with PCOS to women not reporting a diagnosis of PCOS. Changes in psychological distress and BMI were also examined.Main Results and the Role Of Chance: Young women reporting a new diagnosis of PCOS were no more likely to increase their vegetable intake or physical activity than women not reporting a PCOS diagnosis. Women newly diagnosed with PCOS were 3.4 times more likely to stop using contraception during the 12-month study period than women without PCOS (14% versus 4%, 95% CI = 2.3 to 5.1, P < 0.001). This difference remained significant after controlling for demographics, chronic conditions associated with PCOS, endometriosis, BMI and psychological distress (P < 0.001).Limitations, Reasons For Caution: All data was self-reported including PCOS diagnosis, assessment of diet quality was limited to vegetable intake only. The exact timing of diagnosis within the 12-month period and whether the women intended to conceive are unknown. The number of women reporting a new diagnosis of PCOS was also relatively small.Wider Implications Of the Findings: These findings suggest that a diagnosis of PCOS may not produce short-term benefits by way of improving health behaviour. The observed reduction in contraception use suggests some women may be at increased risk of unplanned pregnancies, highlighting the importance of counselling about contraceptive needs. Both potential benefits and harms must be considered when determining the appropriateness of a PCOS diagnosis.Study Funding/competing Interest(s): The Australian Longitudinal Study on Women's Health is funded by the Australian Government Department of Health. BWM reports consultancy for ObsEva, Merck, Merck KGaA and Guerbet. No further competing interests exist.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Is age at natural menopause (ANM) associated with the development of multiple chronic conditions (multimorbidity) in postmenopausal life?Summary Answer: Women with premature menopause experience increased odds of developing individual chronic conditions and multimorbidity.What Is Known Already: ANM is considered as a marker of age-related morbidity and mortality in postmenopausal life. Multimorbidity affects more than 60% of older women and has been recognized as the most common 'chronic condition'. Few studies have examined the association between ANM and the development of multimorbidity.Study Design, Size, Duration: A prospective national cohort study of 11 258 Australian women, aged 45-50 years in 1996. Women were followed from 1996 to 2016.Participants/materials, Setting, Methods: Information about ANM and 11 chronic conditions (diabetes, hypertension, heart disease, stroke, arthritis, osteoporosis, asthma, chronic obstructive pulmonary disease, depression, anxiety and breast cancer) were estimated approximately every 3 years. Multimorbidity is defined as 2 or more of these 11 conditions. Generalized estimating equations were used to link the categorical ANM with individual chronic conditions and multimorbidity.Main Results and the Role Of Chance: Among 5107 women reporting ANM, 2.3% experienced premature menopause (≤40 years) and 55.1% developed multimorbidity. Compared with women who experienced menopause at age 50-51 years, women with premature menopause had twice the odds of experiencing multimorbidity by age 60 (OR = 1.98, 95% CI 1.31 to 2.98) and three times the odds of developing multimorbidity in their 60s (OR = 3.03, 95% CI 1.62 to 5.64). Women with premature menopause also experienced higher incidence of most individual chronic conditions.Limitations, Reasons For Caution: The main limitation of this study was the use of self-reported data, but with repeated assessments from prospective study design and the validity of most of the chronic conditions from hospital data, the potential for non-differential misclassification is minimized.Wide Implications Of the Findings: To our knowledge, this is the first study to assess the association of premature menopause and development of multimorbidity in a larger national cohort of mid-aged women. Health professionals should consider comprehensive screening and assessment of risk factors for multimorbidity when treating women who experienced premature menopause.Study Funding/competing Interest(s): The Australian Longitudinal Study on Women's Health was supported by the Australian Government Department of Health. X.X. is funded by an International Postgraduate Research Scholarship from the Australian government and a UQ Centennial Scholarship from The University of Queensland. G.D.M. is supported by the National Health and Medical Research Council Principal Research Fellowship (APP1121844). None of the authors has any conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Objective: Healthcare accreditation surveyors are well positioned to gain access to hospitals and apply their existing data collection skills to research. Consequently, we contracted and trained a surveyor cohort to collect research data for the Deepening our Understanding of Quality in Australia (DUQuA) project. The aim of this study is to explore and compare surveyors' perceptions and experiences in collecting quality and safety data for accreditation and for health services research.Design: A qualitative, comparative study.Setting and Participants: Ten surveyors participated in semi-structured interviews, which were audio recorded, transcribed and coded using Nvivo11. Interview transcripts of participants were analysed thematically and separately, providing an opportunity for comparison and for identifying common themes and subthemes.Intervention(s): None.Main Outcome Measure(s): Topics addressed data collection for healthcare accreditation and research, including preparation and training, structure, organization, attitudes and behaviours of staff and perceptions of their role.Results: Five themes and ten subthemes emerged from the interviews: (1) overlapping facilitators for accreditation and research data collection, (2) accreditation-specific facilitators, (3) overlapping barriers for accreditation and research data collection, (4) research data collection-specific barriers and (5) needs and recommendations. Subthemes were (1.1) preparation and training availability, (1.2) prior knowledge and experiences; (2.1) ease of access, (2.2) high staff engagement, (3.1) time, (4.1) poor access and structure, (4.2) lack of staff engagement, (4.3) organizational changes; (5.1) short-notice accreditation and (5.2) preparation for future research.Conclusions: Although hospital accreditation and research activities require different approaches to data collection, we found that suitably trained accreditation surveyors were able to perform both activities effectively. The barriers surveyors encountered when collecting data for research provide insight into the challenges that may be faced when visiting hospitals for short-notice accreditation. [ABSTRACT FROM AUTHOR]

Introduction: The detection of harmful alcohol use and the delivery of brief advice in primary care are less than optimal. Given limited health care resources, deciding where best to allocate funding to optimize health outcomes is imperative. A simple data-based tool could be useful when access to specialist health economic advice is unavailable. This study aimed to examine the utility of a simple data-based calculator to facilitate priority setting in general practice for reducing alcohol-related harm.Methods: A simple algorithm was developed within Microsoft Excel to allow comparison of hypothetical intervention scenarios that aimed to increase detection and brief advice for harmful alcohol use in general practice. The calculator accommodated varying implementation costs, size of effect and reach for each scenario created. The incremental costs of the intervention scenarios, the incremental number of successes (i.e. abstinence or drinking at safe levels) and the incremental costs-effectiveness ratio (ICER) were calculated for each hypothetical scenario and compared with a usual care scenario.Results: In the hypothetical scenarios modelled, increasing both the detection of harmful alcohol consumption and the provision of brief advice produced the greatest number of incremental successes above baseline. Increasing detection alone produced fewer incremental successes but was the most cost-effective approach, as indicated by the lowest ICER.Discussion: The data-based calculator provides a simple method of exploring reach and cost-effectiveness outcomes without the need for any specific skills. Although this approach has limitations, the calculator can be used by decision makers to guide intervention planning. [ABSTRACT FROM AUTHOR]

Background: Increasing numbers of GPs are reducing the hours they work in clinical practice. The reasons for and implications of this are not well-understood.Objective: To investigate how the demands of general practice, especially new time pressures, impact GPs' professional and personal lives and work hour choices.Method: Using a grounded theory approach, we conducted 26 in-depth interviews with GPs working in Australia.Results: Time-bound consultation windows, the complexity of patients presenting to general practice and consequent administrative and emotional burdens placed upon GPs combined to increase time pressures and an intensifying clinical load. Many GPs also strove to sequester time for family and reported burnout and poor health along with abiding concerns for quality of care.Conclusion: This study suggests a need for new policies on how clinical consultations are timed and remunerated in keeping with a changed GP demography, new demands and a more complex patient care profile. [ABSTRACT FROM AUTHOR]

Background: Increasing numbers of older people are receiving home nursing support for medication management to enable them to remain living at home. Home nursing clients frequently experience medication errors and adverse medication events. There has been little study of how medication management processes and interdisciplinary teamwork impact on medication management in the home nursing setting.Objective: To explore medication management processes and describe barriers and challenges from the perspective of community nurses, community pharmacists and GPs involved in the provision of medication management services for home nursing clients.Methods: Focus groups, in-depth interviews and stakeholder consultations were conducted with a convenience sample of community nurses, community pharmacists and GPs. Data were analysed using the framework approach (a deductive thematic analysis) to identify issues affecting the delivery of medication management services.Results: Ten focus groups, 12 in-depth interviews and 5 stakeholder consultation meetings were conducted with 86 health practitioners (55 community nurses, 17 GPs, 10 community pharmacists and 4 nurse managers). Participants highlighted a range of barriers and challenges associated with medication management for home nursing clients, including deficiencies in interdisciplinary communication; problems related to organizational or workplace policies, processes and systems; and ineffective team function. The negative impacts of these were recognized as compromised client safety, reduced workforce efficiency and productivity and compromised interprofessional relationships.Conclusion: Barriers and challenges with medication management for home nursing clients and associated negative impacts were identified. Strategies are needed to improve interdisciplinary medication management and medication safety in the home nursing setting. [ABSTRACT FROM AUTHOR]

Background: The latest review of studies on multimorbidity patterns showed high heterogeneity in the methodology for identifying groups of multimorbid conditions. However, it is unclear how analytical methods used influence the identified multimorbidity patterns.Methods: We undertook a systematic review of analytical methods used to identify multimorbidity patterns in PubMed and EMBASE from their inception to January 2017. We conducted a comparison analysis to assess the effect the analytical methods had on the multimorbidity patterns identified, using the Australian National Health Survey (NHS) 2007-08 data.Results: We identified 13 194 studies and excluded 13 091 based on titles/abstracts. From the full-text reviews of the 103 remaining publications, we identified 41 studies that used five different analytical methods to identify multimorbid conditions in the studies. Thirty-seven studies (90%) adopted either the factor-analysis or hierarchical-clustering methods, but heterogeneity arises for the use of different proximity measures within each method to form clusters. Our comparison analysis showed the variation in identified groups of multimorbid conditions when applying the methods to the same NHS data. We extracted main similarities among the groupings obtained by the five methods: (i) cardiovascular and metabolic diseases, (ii) mental health problems and (iii) allergic diseases.Conclusion: We showed the extent of effects for heterogeneous analytical methods on identification of multimorbidity patterns. However, more work is needed to guide investigators for choosing the best analytical method to improve the validity and generalizability of findings. Investigators should also attempt to compare results obtained by various methods for a consensus grouping of multimorbid conditions. [ABSTRACT FROM AUTHOR]

Background: Chlamydia is the most common notifiable sexually transmissible infection in Australia. Left untreated, it can develop into pelvic inflammatory disease and infertility. The majority of notifications come from general practice and it is ideally situated to test young Australians.Objectives: The Australian Chlamydia Control Effectiveness Pilot (ACCEPt) was a multifaceted intervention that aimed to reduce chlamydia prevalence by increasing testing in 16- to 29-year-olds attending general practice. GPs were interviewed to describe the effectiveness of the ACCEPt intervention in integrating chlamydia testing into routine practice using Normalization Process Theory (NPT).Methods: GPs were purposively selected based on age, gender, geographic location and size of practice at baseline and midpoint. Interview data were analysed regarding the intervention components and results were interpreted using NPT.Results: A total of 44 GPs at baseline and 24 at midpoint were interviewed. Most GPs reported offering a test based on age at midpoint versus offering a test based on symptoms or patient request at baseline. Quarterly feedback was the most significant ACCEPt component for facilitating a chlamydia test.Conclusions: The ACCEPt intervention has been able to moderately normalize chlamydia testing among GPs, although the components had varying levels of effectiveness. NPT can demonstrate the effective implementation of an intervention in general practice and has been valuable in understanding which components are essential and which components can be improved upon. [ABSTRACT FROM AUTHOR]

Background: Disadvantage rarely manifests as a single event, but rather is the enduring context in which a child's development unfolds. We aimed to characterize patterns of stability and change in multiple aspects of disadvantage over the childhood period, in order to inform more precise and nuanced policy development.Methods: Participants were from the Longitudinal Study of Australian Children birth cohort (n = 5107). Four lenses of disadvantage (sociodemographic, geographic environment, health conditions and risk factors), and a composite of these representing average exposure across all lenses, were assessed longitudinally from 0 to 9 years of age. Trajectory models identified groups of children with similar patterns of disadvantage over time for each of these lenses and for composite disadvantage. Concurrent validity of these trajectory groups was examined through associations with academic performance at 10-11 years.Results: We found four distinct trajectories of children's exposure to composite disadvantage, which showed high levels of stability over time. In regard to the individual lenses of disadvantage, three exhibited notable change over time (the sociodemographic lens was the exception). Over a third of children (36.3%) were exposed to the 'most disadvantaged' trajectory in at least one lens. Trajectories of disadvantage were associated with academic performance, providing evidence of concurrent validity.Conclusions: Children's overall level of composite disadvantage was stable over time, whereas geographic environments, health conditions and risk factors changed over time for some children. Measuring disadvantage as uni-dimensional, at a single time point, is likely to understate the true extent and persistence of disadvantage. [ABSTRACT FROM AUTHOR]

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self-reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially influenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use. [ABSTRACT FROM AUTHOR]

Background: Acute sore throat is a common condition presenting to family practitioners. It is usually self-limiting, with antibiotic treatment recommended only for high-risk presentations. Overprescribing of antibiotics contributes to individual and community resistance. Learning to prescribe in the context of diagnostic uncertainty and patient pressures is a challenge for early-career doctors. Prescribing habits develop early and tend not to change with time.Objective: To establish the prevalence and associations of antibiotic prescribing for acute sore throat by Australian vocational trainees in family practice.Method: A cross-sectional analysis of data from the Registrar Clinical Encounters in Training (ReCEnT) study. This ongoing, multicentre prospective cohort study documents the nature of trainees' consultation-based clinical experiences. Univariate and logistic regression analyses were conducted on data recorded in consultations for sore throat in nine collection periods during 2010-14.Results: Data from 856 individual trainees (response rate 95.2%) were analysed. Sore throat was managed in 2.3% encounters. Antibiotics were prescribed for 71.5% of sore throat diagnoses. The variables associated with prescribing were inner-regional location and higher socio-economic area. There was no significant association with younger age of patient or greater trainee experience. If an antibiotic was prescribed, the trainee was more likely to seek information from guidelines or a supervisor.Conclusions: The high frequency of antibiotic prescribing and the lack of attenuation in prescribing with increased experience suggest current educational interventions and the apprenticeship model of training is not fostering appropriate practice in this important clinical area. Targeted educational interventions, for supervisors as well as trainees, are indicated. [ABSTRACT FROM AUTHOR]

Background: Detection of lifestyle risk factors by GPs is the first step required for intervention. Despite significant investment in preventive health care in general practice, little is known about whether GP detection of lifestyle risk factors have improved over time.Objectives: To examine whether sensitivity and specificity of GP detection of smoking, risky alcohol consumption and overweight and obesity has increased in patients presenting to see their GP, by comparing results from four Australian studies conducted between 1982 and 2011.Methods: Demographic characteristics of patient and GP samples and the prevalence, sensitivity and specificity of detection of each risk factor were extracted from published studies. Differences between GP and patient sample characteristics were examined. To identify trends over time in prevalence of risk factors, sensitivity and specificity of detection across studies and the Cochran-Armitage test for trend were calculated for each risk factor for the overall sample and by male and female subgroups.Results: There were no statistically significant changes in the sensitivity of GP detection of smoking or overweight or obesity over time. Specificity of detection of smoking increased from 64.7% to 98% (P < 0.0001) and decreased for overweight or obesity from 92% to 89% (P = 0.01). There was a small decrease in the sensitivity of detection of alcohol consumption (P = 0.02) and an increase in specificity (P = 0.01).Conclusions: Despite significant investment to increase GP detection and intervention for lifestyle risk factors, accurate detection of smoking, risky alcohol consumption and overweight and obesity occurs for less than two-thirds of all patients. [ABSTRACT FROM AUTHOR]

Background: there are several different frailty measures available for identifying the frail elderly. However, their predictive performance in an Australian population has not been examined. Objective: to examine the predictive performance of four internationally validated frailty measures in an older Australian population. Methods: a retrospective study in the Australian Longitudinal Study of Ageing (ALSA) with 2,087 participants. Frailty was measured at baseline using frailty phenotype (FP), simplified frailty phenotype (SFP), frailty index (FI) and prognostic frailty score (PFS). Odds ratios (OR) were calculated to measure the association between frailty and outcomes at Wave 3 including mortality, hospitalisation, nursing home admission, fall and a combination of all outcomes. Predictive performance was measured by assessing sensitivity, specificity, positive and negative predictive values (PPVand NPV) and likelihood ratio (LR). Area under the curve (AUC) of dichotomised and the multilevel or continuous model of the measures was examined. Results: prevalence of frailty varied from 2% up to 49% between the measures. Frailty was significantly associated with an increased risk of any outcome, OR (95% confidence interval) for FP: 1.9 (1.4-2.8), SFP: 3.6 (1.5-8.8), FI: 3.4 (2.7-4.3) and PFS: 2.3 (1.8-2.8). PFS had high sensitivity across all outcomes (sensitivity: 55.2-77.1%). The PPV for any outcome was highest for SFP and FI (70.8 and 69.7%, respectively). Only FI had acceptable accuracy in predicting outcomes, AUC: 0.59-0.70. Conclusions: being identified as frail by any of the four measures was associated with an increased risk of outcomes; however, their predictive accuracy varied. [ABSTRACT FROM AUTHOR]

Background: The Seven Countries Study in the 1960s showed very low mortality from coronary heart disease (CHD) in Japan, which was attributed to very low levels of total cholesterol. Studies of migrant Japanese to the USA in the 1970s documented increase in CHD rates, thus CHD mortality in Japan was expected to increase as their lifestyle became Westernized, yet CHD mortality has continued to decline since 1970. This study describes trends in CHD mortality and its risk factors since 1980 in Japan, contrasting those in other selected developed countries.Methods: We selected Australia, Canada, France, Japan, Spain, Sweden, the UK and the USA. CHD mortality between 1980 and 2007 was obtained from WHO Statistical Information System. National data on traditional risk factors during the same period were obtained from literature and national surveys.Results: Age-adjusted CHD mortality continuously declined between 1980 and 2007 in all these countries. The decline was accompanied by a constant fall in total cholesterol except Japan where total cholesterol continuously rose. In the birth cohort of individuals currently aged 50-69 years, levels of total cholesterol have been higher in Japan than in the USA, yet CHD mortality in Japan remained the lowest: >67% lower in men and > 75% lower in women compared with the USA. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries.Conclusions: Decline in CHD mortality despite a continuous rise in total cholesterol is unique. The observation may suggest some protective factors unique to Japanese. [ABSTRACT FROM AUTHOR]

Background Extended drought conditions in south-east Queensland during the early 2000s have resulted in a culture of water harvesting and legislated water restrictions. Aedes notoscriptus is a container-breeding mosquito vector of Ross River and Barmah Forest viruses. Methods From 2008–2009, the larval habitats and seasonal abundance of domestic container-breeding mosquitoes were recorded from three suburbs of Brisbane. A knowledge, attitudes and practice questionnaire was administered to householders. A low-cost, desktop methodology was used to predict the proportion of shaded premises compared with front-of-property estimates. Results We highlight changes in the frequency of container categories for A. notoscriptus as a response to human behavioural changes to drought. Garden accoutrements, discarded household items and water storage containers accounted for 66.2% (525/793) of positive containers and 77.5% (73 441/94 731) of all immature mosquitoes. Of all household premises surveyed, 52.6% (550/1046) contained rainwater tanks and 29.4% (308/1046) harvested water in other containers, contrasting with a previous 1995 survey where neither category was observed. Both Premise Condition Index and shade directly correlated with positive premises. Conclusions Human response to drought has resulted in new habitats for domestic container-breeding mosquitoes. This recent trend of prolific water storage is similar to earlier years (1904–1943) in Brisbane when Aedes aegypti was present and dengue epidemics occurred. [ABSTRACT FROM PUBLISHER]

SUMMARY The GOCE mission, a part of ESA's Living Planet Programme, aims at improved gravity field modelling at high spatial resolution. On-board GOCE a gradiometer, in combination with a scientific on-board GPS receiver, measures the earth's gravity field with unprecedented accuracy. These measurements have been used to compute GOCE gravity field solutions and combined GOCE/GRACE solutions. The main difference between the solutions is how they incorporate the required a priori information, which consists either of existing gravity field models or Kaula's rule for the signal variances of the gravity field. We assessed four series of models by comparing the gravity gradients they predict with the measured GOCE gradients. The analysis of the gravity gradients fits may reveal differences between the different solutions that can be attributed to the solution strategy, assuming that the measurement errors are homogeneous. We compared the GOCE gradients with existing state-of-the-art global gravity field models and conclude that the gradient errors are indeed globally homogeneous, with the exception of the cross-track gradient especially south of Australia. Furthermore, we find that the use of existing global gravity field models as a priori information should be avoided because this may increase the gradient residuals in spatial and spectral domain. Finally, we may conclude that the GOCE and GRACE data are compatible and complementary. [ABSTRACT FROM AUTHOR]

The material transformation of the Chinese economy is forcing a concomitant process of political adjustment-and not just in China. Other states are being forced to accommodate the 'rise of China'. In this context, this article first presents a comparative analysis of China's impact on two countries, Australia and South Africa, which have little in common other than a wealth of natural resources and a possible status as middle powers; this is a particularly useful exercise because these states are geographically distant and have very different political structures and general developmental histories. Second, the authors consider how China's bilateral ties look from a Chinese perspective in these two very different relationships. Such an analysis serves as a reminder that resource dependency is a two-way street. The article argues that underlying material realities are constraining and to some extent determining the domestic and foreign policies of three very different states that otherwise have little in common. [ABSTRACT FROM AUTHOR]

The authors investigated the health consequences of marital separation and whether the partners who initiated the separation had better health than those who did not. The data came from the Households, Income and Labour Dynamics in Australia (HILDA) panel study (2001–2007), comprising an analytic sample of 1,786 men and 2,068 women who were in their first marriages in 2001. For participants who separated, the authors distinguished between self-initiated, partner-initiated, and jointly initiated separations. Using linear random-intercept models, they examined scores on the 8 physical and mental health dimensions of Short Form 36, with scale scores ranging from 0 to 100. The results indicated that in general, men who separated had a decline in health, although this was more pronounced for mental dimensions than for physical dimensions. Among separated men, those whose partner initiated the separation had poorer mental health than those for whom the separation was self-initiated or jointly initiated (−4.61). Women's physical health improved with separation, but their mental health declined. For separated women, those whose partner initiated the separation had lower scores on the general health (−5.39), role-emotional (−11.08), and mental health (−7.18) scales than women who self-initiated separation. The health consequences of separation were less severe for self- or jointly initiated separations, suggesting that not all marital dissolutions are equally bad for health. [ABSTRACT FROM PUBLISHER]

In relation to mental health, it is clear that medicalized underpinnings, the provision of a clin- ically orientated evidence base for practice and the need to contain `risk' continue to be prior- itized, particularly when compulsory intervention is considered. This is despite the increasing influence of a citizenship and social justice agenda which is being promoted by psychiatrists involved in the development of `postpsychiatry', as well as by service users/survivors. These drivers are not mutually exclusive, but in the context of compulsory treatment, there are clear tensions. In this article, the policy surrounding mental health and compulsory intervention in Australia and in England and Wales is explored. In the context of this discussion, three ways in which current government policy can be interpreted are examined and links made between these interpretations and different ways of viewing the relationship between mental health and community capacity building. With regard to social work practice, it is argued that a response to mental ill health which concentrates on an individualized `diagnose and treat' approach, which particularly comes to the fore at times of compulsory intervention, has limited capacity to facilitate community engagement, foster social inclusion and generate reciprocal dynamics between positive mental health and community capacity building. [ABSTRACT FROM AUTHOR]