National Health Council Research Articles

Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: cohort study of UK Biobank participants.

STUDY QUESTIONWhat is the association between menopausal hormone therapy (MHT) and cause-specific mortality?SUMMARY ANSWERSelf-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes.WHAT IS KNOWN ALREADYEvidence from the Women’s Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality.STUDY DESIGN, SIZE, DURATIONCohort study (the UK Biobank), 178 379 women, recruited in 2006–2010.PARTICIPANTS/MATERIALS, SETTING, METHODSPostmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality.MAIN RESULTS AND THE ROLE OF CHANCEAmong the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50–52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45–49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6–20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74).LIMITATIONS, REASONS FOR CAUTIONSelf-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT.WIDER IMPLICATIONS OF THE FINDINGSThe current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation.STUDY FUNDING/COMPETING INTEREST(S)This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

State-wide genomic epidemiology investigations of COVID-19 in healthcare workers in 2020 Victoria, Australia: Qualitative thematic analysis to provide insights for future pandemic preparedness

SummaryBackgroundCOVID-19 has affected many healthcare workers (HCWs) globally. We performed state-wide SARS-CoV-2 genomic epidemiological investigations to identify HCW transmission dynamics and provide recommendations to optimise healthcare system preparedness for future outbreaks.MethodsGenome sequencing was attempted on all COVID-19 cases in Victoria, Australia. We combined genomic and epidemiologic data to investigate the source of HCW infections across multiple healthcare facilities (HCFs) in the state. Phylogenetic analysis and fine-scale hierarchical clustering were performed for the entire dataset including community and healthcare cases. Facilities provided standardised epidemiological data and putative transmission links.FindingsBetween March-October 2020, approximately 1,240 HCW COVID-19 infection cases were identified; 765 are included here, requested for hospital investigations. Genomic sequencing was successful for 612 (80%) cases. Thirty-six investigations were undertaken across 12 HCFs. Genomic analysis revealed that multiple introductions of COVID-19 into facilities (31/36) were more common than single introductions (5/36). Major contributors to HCW acquisitions included mobility of staff and patients between wards and facilities, and characteristics and behaviours of patients that generated numerous secondary infections. Key limitations at the HCF level were identified.InterpretationGenomic epidemiological analyses enhanced understanding of HCW infections, revealing unsuspected clusters and transmission networks. Combined analysis of all HCWs and patients in a HCF should be conducted, supported by high rates of sequencing coverage for all cases in the population. Established systems for integrated genomic epidemiological investigations in healthcare settings will improve HCW safety in future pandemics.FundingThe Victorian Government, the National Health and Medical Research Council Australia, and the Medical Research Future Fund.

1147-P: Trends in Diabetes-Related Foot Disease Hospitalization, Revascularization, and Amputations in Australia 20to 2019

Hospitalization for diabetes-related foot disease adds considerable burden for people living with diabetes and often leads to lower extremity amputation. We evaluated trends in the incidence of foot disease related hospital admission, revascularization and amputation procedures among people with type 1 and type 2 diabetes in Australia from 2010-2019. We included 70,766 people with type 1, and 1.1 million people with type 2 diabetes from the Australian diabetes registry (55% male) . We linked the diabetes registry to hospital admissions data to obtain the number of hospital admissions for foot disease, revascularization and amputation procedures. We estimated the annual incidence rates, using people with diabetes as the denominator, and evaluated trends over time with Joinpoint regression. In type 1 diabetes, rates of admission for foot disease and revascularization increased, while amputation rates were relatively stable (Table) . In type 2 diabetes, rates of foot disease admission and revascularization increased. While above the knee amputations decreased, below the knee amputations were stable, and foot and toe amputations increased. Average annual percent changes were generally higher for men than women (i.e. men showed greater increases or less of a decrease over time) . These findings highlight the importance of improving management of diabetes-related foot disease. Disclosure M.Quigley: None. J.I.Morton: None. P.A.Lazzarini: None. J.E.Shaw: Advisory Panel; Abbott Diagnostics, AstraZeneca, Eli Lilly and Company, Pfizer Inc., Roche Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi. D.J.Magliano: None. Funding MQ is supported by an Australian Government Research Training Program (RTP) Scholarship. JIM is supported by an Australian Government Research Training Program (RTP) Scholarship and Monash Graduate Excellence Scholarship. PAL is supported by a National Health and Medical Research Council Early Career Fellowship. JES is supported by a National Health and Medical Research Council Investigator Grant. DJM is supported by a National Health and Medical Research Council Senior Research Fellowship. This work is partially supported by the Victorian Government’s Operational Infrastructure Support Program.

1139-P: The Association between Age of Onset of Type 2 Diabetes and the Long-Term Risk for Major Diabetes-Related Complications

We evaluated the association between age of onset of type 2 diabetes and the risk for major diabetes complications. We included 1.1 million people with type 2 diabetes from the Australian diabetes registry, followed from 2010-2019. We evaluated the incidence of hospitalization for, or death from, myocardial infarction (MI) , stroke, and heart failure (HF) , and hospitalization for lower extremity amputation (LEA) ; the incidence of end-stage kidney disease (ESKD; including kidney replacement therapy or death from ESKD) ; and all-cause mortality (ACM) . Poisson regression was used to model rates by age of diabetes onset, current age, and diabetes duration. During 6.9 million person-years of follow-up, 72338, 46533, 101023, 20024, 13331, and 203542 MI, stroke, HF, LEA, ESKD, and ACM events occurred, respectively. The risk for all outcomes increased exponentially with diabetes duration (Figure) . The effects of age and duration differed for each: age was the stronger risk factor for MI, stroke, HF, and ACM, while duration was the predominant determinant of ESKD and LEA risk. At a given age, a 10-year younger age of onset was associated with a 1.1-1.5-fold increased risk of stroke and ACM, a 1.5-2-fold increased risk of MI and HF, and a 2-4-fold increased risk of LEA and ESKD. Thus, the increase in prevalence of young-onset type 2 diabetes may shift the burden of diabetes complications in coming decades. Disclosure J.I.Morton: None. P.Lazzarini: None. K.Polkinghorne: None. D.J.Magliano: None. J.E.Shaw: Advisory Panel; Abbott Diagnostics, AstraZeneca, Eli Lilly and Company, Pfizer Inc., Roche Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi. Funding JIM is supported by an Australian Government Research Training Program (RTP) Scholarship and Monash Graduate Excellence Scholarship. PAL is supported by a National Health and Medical Research Council Early Career Fellowship. DJM is supported by a National Health and Medical Research Council Senior Research Fellowship. JES is supported by a National Health and Medical Research Council Investigator Grant. This work is partially supported by the Victorian Government’s Operational Infrastructure Support Program.

A review of Australian Government funding of parenting intervention research

ObjectivesParenting is central to children's optimal development and accounts for a substantial proportion of the variance in child outcomes, including up to 40% of child mental health. Parenting is also one of the most modifiable, proximal, and direct factors for preventing and treating a range of children's problems and enhancing wellbeing. To determine the effectiveness of new approaches to parenting intervention, and to evaluate how to optimise reach and uptake, sufficient funding must be allocated for high quality research. MethodWe reviewed funding awarded by the National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) for parenting intervention research during 2011–2020. ResultsParenting intervention research received 0.25% of the NHMRC and ARC research budgets. ConclusionsThere is a substantial mismatch between the funding of parenting intervention research and the impact of improved parenting on short‐ and long‐term child outcomes. To rectify this, it is critical that Australian Government funding schemes include parenting interventions as priority areas for funding. Implications for public healthChanges in allocation of funding to parenting research will support the establishment of evidence for the effective development, implementation and dissemination of parenting interventions to maximise health outcomes for children and their families.

The Role of Child Diets in the Association between Pre-pregnancy Diets and Childhood Behavioral Problems: A Mediation Analysis

ObjectivesTo quantify the mediating role of childhood diets in the association between maternal diets before pregnancy and offspring behavioral problems.MethodsThis study included 1448 mother-child pairs from the Australian longitudinal study on women's health and its sub-study mothers and their children's health. The healthy eating index score was constructed using a semi-quantitative and validated 101-item food-frequency questionnaire. Childhood behavioral problems were assessed using the strengths and difficulties questionnaire. Three dietary patterns were identified using principal component analysis to explore childhood dietary patterns (high fats and sugar; prudent diets; and diary). A causal inference framework for mediation analysis was used to quantify the mediating role of childhood diets in the association between pre-pregnancy diets and the risk of offspring behavioral problems.ResultsWe found a 20% of the total effect of the poor adherence to pre-pregnancy diet quality on the risk of offspring behavioral problems was mediated through childhood high consumptions of fats and sugar. No clear mediating effect through prudent, and diary childhood diets was observed.ConclusionsThis study suggests that childhood high fats and sugar consumption may contribute to the total effects of the pre-pregnancy diets on the risk of childhood behavioral problems.Funding SourcesThe ALSWH is funded by the Australian Government Department of Health. MatCH is funded by the National Health and Medical Research Council (NHMRC) project grant. Dereje Gete is supported by the University of Queensland Research Training Scholarship. Gita Mishra holds the Australian Health and Medical Research Council Principal Research Fellowship.

Cardiometabolic multimorbidity, genetic risk, and dementia: a prospective cohort study

SummaryBackgroundIndividual cardiometabolic disorders and genetic factors are associated with an increased dementia risk; however, the relationship between dementia and cardiometabolic multimorbidity is unclear. We investigated whether cardiometabolic multimorbidity increases the risk of dementia, regardless of genetic risk, and examined for associated brain structural changes.MethodsWe examined health and genetic data from 203 038 UK Biobank participants of European ancestry, aged 60 years or older without dementia at baseline assessment (2006–10) and followed up until March 31, 2021, in England and Scotland and Feb 28, 2018, in Wales, as well as brain structural data in a nested imaging subsample of 12 236 participants. A cardiometabolic multimorbidity index comprising stroke, diabetes, and myocardial infarction (one point for each), and a polygenic risk score for dementia (with low, intermediate, and high risk groups) were calculated for each participant. The main outcome measures were incident all-cause dementia and brain structural metrics.FindingsThe dementia risk associated with high cardiometabolic multimorbidity was three times greater than that associated with high genetic risk (hazard ratio [HR] 5·55, 95% CI 3·39–9·08, p<0·0001, and 1·68, 1·53–1·84, p<0·0001, respectively). Participants with both a high genetic risk and a cardiometabolic multimorbidity index of two or greater had an increased risk of developing dementia (HR 5·74, 95% CI 4·26–7·74, p<0·0001), compared with those with a low genetic risk and no cardiometabolic conditions. Crucially, we found no interaction between cardiometabolic multimorbidity and polygenic risk (p=0·18). Cardiometabolic multimorbidity was independently associated with more extensive, widespread brain structural changes including lower hippocampal volume (F2, 12 110 = 10·70; p<0·0001) and total grey matter volume (F2, 12 236 = 55·65; p<0·0001).InterpretationCardiometabolic multimorbidity was independently associated with the risk of dementia and extensive brain imaging differences to a greater extent than was genetic risk. Targeting cardiometabolic multimorbidity might help to reduce the risk of dementia, regardless of genetic risk.FundingWellcome Trust, Alzheimer's Research UK, Alan Turing Institute/Engineering and Physical Sciences Research Council, the National Institute for Health Research Applied Research Collaboration South West Peninsula, National Health and Medical Research Council, JP Moulton Foundation, and National Institute on Aging/National Institutes of Health.

Correspondence to " Emollients in infancy to prevent atopic dermatitis: A systematic review and meta‐analysis"

MK, SC, RP and HCW report no conflict of interest. AJL reports: My institution has received National Health and Medical Research Council grant and fellowship funding to undertake a skin barrier intervention study. I also declare that Primus Pharmaceuticals and PuraCap Pharmaceuticals have donated EpiCream (a skin barrier treatment) for use in these studies, free of charge. I have also received an investigator-initiated grant from GSK for unrelated research. RJB reports: I have received personal payment for participating in advisory boards for DBV Technologies and Prota Therapeutics, which develop allergy diagnostics or treatments; have received payment for designing a clinical trial for Dairy Goat Co-operative; and have received personal payment for providing expert testimony in a class action related to an infant formula health claim concerning the development of allergic conditions.

Common risk variants for epilepsy are enriched in families previously targeted for rare monogenic variant discovery.

SummaryBackgroundThe epilepsies are highly heritable conditions that commonly follow complex inheritance. While monogenic causes have been identified in rare familial epilepsies, most familial epilepsies remain unsolved. We aimed to determine (1) whether common genetic variation contributes to familial epilepsy risk, and (2) whether that genetic risk is enriched in familial compared with non-familial (sporadic) epilepsies.MethodsUsing common variants derived from the largest epilepsy genome-wide association study, we calculated polygenic risk scores (PRS) for patients with familial epilepsy (n = 1,818 from 1,181 families), their unaffected relatives (n = 771), sporadic patients (n = 1,182), and population controls (n = 15,929). We also calculated separate PRS for genetic generalised epilepsy (GGE) and focal epilepsy. Statistical analyses used mixed-effects regression models to account for familial relatedness, sex, and ancestry.FindingsPatients with familial epilepsies had higher epilepsy PRS compared to population controls (OR 1·20, padj = 5×10−9), sporadic patients (OR 1·11, padj = 0.008), and their own unaffected relatives (OR 1·12, padj = 0.01). The top 1% of the PRS distribution was enriched 3.8-fold for individuals with familial epilepsy when compared to the lowest decile (padj = 5×10−11). Familial PRS enrichment was consistent across epilepsy type; overall, polygenic risk was greatest for the GGE clinical group. There was no significant PRS difference in familial cases with established rare variant genetic etiologies compared to unsolved familial cases.InterpretationThe aggregate effects of common genetic variants, measured as polygenic risk scores, play an important role in explaining why some families develop epilepsy, why specific family members are affected while their relatives are not, and why families manifest specific epilepsy types. Polygenic risk contributes to the complex inheritance of the epilepsies, including in individuals with a known genetic etiology.FundingNational Health and Medical Research Council of Australia, National Institutes of Health, American Academy of Neurology, Thomas B and Jeannette E Laws McCabe Fund, Mirowski Family Foundation.

Nurse- and midwife-led trials in Australia and New Zealand: Scoping review protocol

BackgroundResearch led by nurses or midwives has the potential to successfully address current issues in clinical care. High-quality randomised controlled trials are needed to inform evidence-based practice; however, nursing and midwifery research has commonly been nonexperimental. Two connected scoping reviews of nurse- and midwife-led randomised controlled trials within Australia and New Zealand will be conducted to highlight potential research directions and identify resources for future research. AimThe purpose of the two reviews is to map the number and types of randomised controlled trials led by nurses or midwives within Australia and New Zealand. MethodsThe concept of interest is randomised controlled trials with a lead principal investigator holding nursing or midwifery credentials. The lead principal investigator must report an institutional affiliation in Australia or New Zealand, and the trial must recruit at a minimum of one site in Australia or New Zealand. Searches for academic literature will be conducted using Pubmed, Emcare, and Scopus. Sources for grey literature will include the Australian New Zealand Clinical Trials Registry, and grant outcomes published by the National Health and Medical Research Council, Medical Research Future Fund, and Health Research Council of New Zealand. Data analysis and presentation will be conducted separately for each review. DiscussionThese reviews will comprehensively map the experimental research activity of nurses and midwives within Australia and New Zealand and highlight potential research directions. From this, strategies to facilitate high quality nurse- and midwife-led trials can be developed, which are vital for informing evidence-based practice.

0474 Three-arm randomised controlled trial of Cognitive Behavioural Therapy for Insomnia, a responsive bassinet, and sleep hygiene for preventing postpartum insomnia: Preliminary findings on maternal insomnia and sleep outcomes (Study for Mother-Infant Sleep)

Abstract Introduction Insomnia symptoms are common during the perinatal period and are linked to adverse parent/infant outcomes. This single-blind 3-arm randomised controlled trial examined how two interventions targeting different mechanisms prevent postpartum insomnia compared to sleep hygiene control. Trial registration: ACTRN12619001166167. Methods Participants were nulliparous females 26-32 weeks gestation with self-reported insomnia symptoms (Insomnia Severity Index [ISI] scores ≥ 8). Participants were randomized 1:1:1 to: (a) a responsive bassinet designed to support infant sleep until 6 months postpartum (RB), (b) therapist-assisted cognitive behavioural therapy for insomnia (CBT-I) delivered during pregnancy and postpartum, or (c) a sleep hygiene booklet (control condition; CTRL). Outcomes were assessed at baseline (T1), 35-36 weeks gestation (T2), and 2, 6, and 12 months postpartum (T3-T5). The primary outcome is ISI scores averaged T3-T5. Secondary outcomes are PROMIS Sleep Disturbance (SDI), Sleep-Related Impairment (SRI), and self-report total sleep time (TST). We report preliminary results on T1-T4 as T5 is ongoing. Multiple regression analyses controlling for baseline outcomes examined group differences at post-baseline timepoints. Results 127 participants were randomised (age M±SD=32.62±3.49; RB = 44, CBT-I = 42, CTRL = 41), and 118 (92.9%) completed T4. Compared to CTRL, CBT-I had lower ISI, SDI, and SRI at T2, T3, and T4 (all p&amp;lt;.05 except p=.07 and .06 for ISI at T3 and T4; Cohen’s d ranges 0.39-0.99); differences in TST were non-significant at all timepoints (all p&amp;gt;.25). The RB condition had significantly longer TST at T4 (40.10 min longer, p=.008, d=.63) compared to CTRL, but these two conditions did not differ significantly on any other measures across all timepoints (p&amp;gt;.22). Conclusion Preliminary findings suggest CBT-I was efficacious in preventing insomnia symptoms and reducing sleep disturbance and sleep-related impairment, but did not increase maternal sleep duration postpartum. Conversely, a responsive bassinet designed to support infant sleep meaningfully increased maternal sleep duration at 6 months postpartum but did not prevent insomnia symptoms. These initial findings suggest that perinatal sleep complaints are a multifactorial problem that likely require multi-component interventions targeting different causes and mechanisms. Support (If Any) National Health and Medical Research Council, Department of Education and Training.

Real-world trends in incidence of bacterial sexually transmissible infections among gay and bisexual men using HIV pre-exposure prophylaxis (PrEP) in Australia following nationwide PrEP implementation: an analysis of sentinel surveillance data

Although data from large implementation trials suggest that sexually transmissible infection (STI) risk increases among gay and bisexual men who initiate HIV pre-exposure prophylaxis (PrEP), there are few data on the trends in population-level STI incidence in the years following widespread PrEP implementation. We aimed to describe trends in bacterial STI incidence among gay and bisexual men using PrEP across Australia in the context of broad PrEP availability through Australia's subsidised medicines scheme. We analysed linked clinical data from HIV-negative gay and bisexual men aged 16 years or older who had been prescribed PrEP across a sentinel surveillance clinical network, including 37 clinics in Australia, between Jan 1, 2016, and Dec 31, 2019. Patients were included if they had STI testing at least twice during the observation period. Repeat testing methods were used to calculate chlamydia, gonorrhoea, syphilis, and any STI incidence rates during individuals' periods of PrEP use. Incidence rate ratios (IRRs) for estimated change in incidence per half calendar year (6-month) period were calculated using negative binomial regression. Secondary analyses compared STI incidence rates across individuals initiating PrEP in each year from 2016 to 2019, as well as by length of time using PrEP (per each additional 6 months of PrEP use). 22 730 men were included in the analyses. During the observation period, 11 351 chlamydia infections were diagnosed in 6630 (30·1%) of 22 034 men over 25 991·2 person-years of PrEP use (incidence rate 43·7 cases [95% CI 42·9-44·5] per 100 person-years). Chlamydia incidence decreased from 48·7 cases per 100 person-years in July-December, 2016, to 42·0 cases per 100 person-years in July-December, 2019 (IRR for estimated change per 6-month period 0·98 [95% CI 0·97-0·99]; p=0·0031). 9391 gonorrhoea infections were diagnosed in 5885 (26·9%) of 21 845 men over 24 858·7 person-years of PrEP use (incidence rate 37·8 cases [95% CI 37·0-38·5] per 100 person-years). Gonorrhoea incidence decreased from 45·5 cases per 100 person-years in July-December, 2016, to 37·2 cases per 100 person-years in July-December, 2019 (IRR 0·97 [95% CI 0·96-0·98]; p<0·0001). Declines in chlamydia and gonorrhoea incidence were most prominent in the first 18 months of observation and incidence was stable thereafter. 2062 syphilis infections were diagnosed in 1488 (7·7%) of 19 262 men over 21 978·9 person-years of PrEP use (incidence rate 9·4 cases [95% CI 9·0-9·8] per 100 person-years). Syphilis incidence increased from 6·2 cases per 100 person-years in July-December, 2016, to 9·8 cases per 100 person-years in July-December, 2019 (IRR 1·08 [95% CI 1·05-1·10]; p<0·0001). Chlamydia and gonorrhoea incidence among gay and bisexual men using PrEP were highest in the early months of PrEP implementation in Australia and stabilised at slightly lower rates thereafter following wider PrEP uptake. Lower prospective STI risk among people initiating PrEP in later years contributed to the observed trends in STI incidence. Widespread PrEP implementation can contribute to increased STI screening and detection. Australian Department of Health, National Health and Medical Research Council.

Online Parenting Intervention for Children's Eating and Mealtime Behaviors: Protocol of a Randomized Controlled Trial.

Introduction: Obesity and overweight are significant health problems among Australian children. Parents play a vital role in establishing healthy eating behaviors in their children. However, parents often experience difficulties in implementing effective parenting practices and lack confidence in their ability to help children adopt these behaviors. This trial will evaluate the efficacy of an online program, Healthy Habits Triple P, in improving children’s snacking and mealtime behaviors and related parenting practices. Methods and analysis: This is a single-blinded, randomized controlled trial for parents of young Australian children aged 2–6 years. Participants will be recruited through childcare centers, social media, online parent forums and existing networks. The participants in the intervention arm will receive access to a web-based parenting intervention in addition to nutrition-related information for parents published by the National Health and Medical Research Council of Australia; those in the control arm will receive nutrition-related information only. After the completion of the study, the parenting intervention will be offered to the control arm. The primary outcome will be improvement in children’s eating habits. The secondary outcomes include parents’ self-efficacy, confidence, children’s mealtime behaviors and mealtime parenting strategies. Both primary and secondary outcomes will be evaluated through online-administered, validated parent-reported questionnaires. We will also undertake a quantitative and qualitative evaluation of the practicality and acceptability of the intervention.

The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia

Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference -7·53 (95% CI -14·45 to 0·60; Cohen's d -0·53). A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited. UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council.

Predictors of poor exercise self-efficacy improvements after cardiac rehabilitation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): SOLVE-CHD Australian Government National Health and Medical Research Council (NHMRC) Synergy Grant [GNT1182301] PhD Scholarships Background/Introduction Building confidence to exercise regularly (exercise self-efficacy (ESE)) in the face of constraints and barriers, is a key goal of cardiac rehabilitation (CR) because such self-efficacy beliefs are predictors of sustained exercise behaviours. Therefore, identifying patient subgroups at risk of poor ESE enables tailoring of CR and appropriate targeting of support interventions. Purpose To identify independent predictors of poor ESE and poor improvements in ESE in CR participants. Methods The study used a prospective observational cohort design and recruited patients with coronary heart disease at CR entry across four sites in Metropolitan Sydney, Australia (2019-2020). Data were also compared for traditional in-person and remote-delivered CR during COVID-19 pandemic restrictions. The Exercise Self Efficacy Scale was used to measure ESE at CR entry and completion, and General Linear Models were used for analyses. Results Participants (n=194) had a mean age of 65.94 (SD 10.46) years, with 80.9% males; and 80.0% were married or partnered, with 23.6% from an ethnic minority background. Referral diagnosis included elective percutaneous coronary intervention (PCI) (40.2%), coronary artery bypass surgery (26.3%), and myocardial infarction with or without PCI (33.5%). At CR entry, the mean ESE score was 24.93 (SD 5.99) points, which improved significantly by completion (p=.027). The GLM of ESE change (Adjusted R2=.247) identified that predictors of less change in ESE scores by CR completion included ethnic minorities (β=2.96, p=.003), not having a spouse or an intimate partner (β=-2.42, p=.023), and attending in-person CR (β=1.75, p=.036). Having higher ESE scores at entry was also associated with less ESE change on completion, such that for every point increase in ESE at entry, there was a reduction of .37 points in change (p&amp;lt;.001). These variables were also the same predictors of poor ESE at CR completion. Conclusions Confidence to exercise improves in CR, and screening for ESE at CR entry enables identification of patients at-risk of poor improvements. Tailoring of interventions to provide appropriate support such as extending CR should be considered for patients from ethnic minorities and those who are single/widowed. Exploring the reasons for differences in outcomes from in-person and remote-delivered CR using appropriate methods should be the focus of future research.

The prevalence and clinical significance of a reduced ventricular ejection fraction in asymptomatic young elite endurance athletes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Health and Medical Research Council of Australia Background Ventricular ejection fraction (EF) is the most widely used parameter to evaluate ventricular systolic function. Endurance athletes presenting with a reduced ventricular EF often raise the question of an underlying dilated or arrhythmogenic cardiomyopathy. The clinical significance of a reduced EF in athletes remains to be elucidated. Purpose To investigate the prevalence and clinical significance of a reduced EF in asymptomatic endurance athletes. Methods Two hundred eighteen asymptomatic young elite endurance athletes were evaluated at baseline. Cardiac magnetic resonance imaging (CMR) was performed to assess cardiac volumes, left ventricular and right ventricular EF (LVEF and RVEF), mass and fibrosis. Athletes with reduced EF (ATrEF) were defined as those having LVEF&amp;lt;50% and/or RVEF&amp;lt;45%. Ventricular systolic and diastolic function were assessed by trans-thoracic echocardiography. A 12-lead ECG and 24-hour holtermonitoring assessed electrical alterations and arrhythmias. In 145 athletes, LV and RV contractile reserve was evaluated by exercise CMR. Cardiopulmonary testing was performed in all athletes to measure maximal oxygen uptake (VO2max). Results Thirty-one ATrEF (14.2%) were compared to 187 athletes with a preserved EF (ATpEF). ATrEF were more frequently males (93 vs 77% male, p=0.033) but did not differ from ATpEF with regard to age (18.8±2.1 vs 18.3±2.1 years, p=0.25). Ten athletes had an isolated reduced LVEF, 10 had an isolated reduced RVEF and 11 had both a reduced LVEF and RVEF. ATrEF had similar end-diastolic volumes and cardiac mass but differed by higher end-systolic volumes. Peak exercise LVEF and RVEF determined by exercise CMR remained lower in ATrEF (68±3 vs 73±4% and 62±6 vs 69±5%, p&amp;lt;0.001) but contractile reserve was greater (ΔLVEF 18±5 vs 14±4% and ΔRVEF 19±5 vs 15±5%, p&amp;lt;0.01). A reduced EF was not associated with lower exercise capacity, in fact VO2max was higher in ATrEF than in ATpEF (65±6 vs 62±9mL/kg/min, p=0.020) and the percentage of predicted VO2max by the Wasserman equation were similar (151±14 vs 149±21%, p=0.533). Fibrosis was present in 3 ATrEF and 18 ATpEF (9.7 vs 9.6%, p=0.993) and was isolated to the RV hinge-points in all but 3 ATpEF who had midmyocardial LV lateral wall fibrosis. LV systolic strain (-17.5±2.0 vs -19±2.1%, p&amp;lt;0.001) was lower in ATrEF whereas RV free wall systolic strain (-24.9±3.7 vs -25.1±3.5%, p=0.776) was similar. Diastolic function was normal in all ATrEF and ATpEF. Pathologic T-wave inversions were present in 2 ATrEF and 13 ATpEF (6.5 vs 7%, p=0.999). Ventricular premature beats (VPB) were infrequent but more prevalent in ATrEF than in ATpEF (2[0-18] vs 1[0-2]/24h, p=0.025; 16.1 vs 2.7% &amp;gt;100/24h, p=0.006). Conclusion A reduced ventricular EF is common in asymptomatic young elite endurance athletes, is more frequent in males but is not associated with structural, functional or electrical abnormalities apart from a minor excess in VPB.

Burden of stroke incidence among atrial fibrillation, valvular heart disease and coronary heart disease patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Health and Medical Research Council of Australia Background The public health burden of stroke has continued to increase in recent decades. In patients with cardiac disease, the risk of stroke is 2-4 times higher than in the general population, and therefore investigating stroke incidence in these patients is important for identifying opportunities for stroke prevention. Purpose We aimed to measure the incidence of stroke in people with atrial fibrillation (AF), valvular heart disease (VHD) or coronary heart disease (CHD) to assess the risk of stroke by age, sex, pre-existing vs new cardiac disease, and nonfatal/fatal status. Methods We used a person-linked hospitalisation/mortality dataset to identify all people hospitalized with AF, VHD or CHD from 1985 to 2017 in a whole-population setting. These cardiac cases were stratified as pre-existing (hospitalised between 1985 and 2012, who were alive at 31st October 2012 with no history of stroke) or new (first-ever cardiac hospitalisation from November 1st, 2012 to October 31st, 2017, with no prior hospitalisation for AF, VHD or CHD, and no history of stroke). Patients aged 20-94 years were included in the study. Pre-existing and new cardiac cases were followed over the 5-year study period (1st November 2012 to 31st December 2017) to identify first-ever stroke events. Age-specific and age-standardised rates (ASR) for stroke incidence were calculated for all cardiac cases combined, and separately for pre-existing and new cases. Results The cohort comprised 175,560 patients. The majority of the cohort had a single cardiac condition (55.7% CHD; 23.0% AF; 5.0% VHD), while 16.3% of patients had multiple cardiac conditions. There were 5,871 (3.3%) first-ever strokes (5.2% in AF patients, 4.0% in VHD, 2.8% in CHD). Stroke incidence ASRs were greater in women than men across each cardiac group and irrespective of the presence of single or multiple cardiac conditions (Figure). This was largely driven by women aged ≥75 years, with stroke incidence being greater in women than men in each cardiac group. In women aged 20-54 years, there was a 4.9-fold higher incidence of stroke in those with multiple versus single cardiac conditions, and this differential appeared to decline with increasing age (Figure). Incidence of non-fatal strokes was greater than fatal stroke in all age groups except among 85-94 year olds. Incidence rates in each cardiac group were between 1.2 and 2.4 times higher in those with new versus pre-existing cardiac disease. Conclusions Stroke incidence is substantial in patients with cardiac disease. Older women with AF and VHD had the highest stroke rates overall, although younger patients with multiple cardiac conditions were also at high risk. These cardiac patients should be targeted for evidence-based management to minimise their stroke risk, especially in the period immediately following diagnosis when risk is highest. Figure Legend. Age-specific and age-standardised stroke incidence rates in all cardiac cases.

Temporal trends in myocardial infarction case fatality: methodological challenges and prevention targets

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Health and Medical Research Council of AustraliaHealy Medical Research Foundation Background Case fatality is an important indicator of severity and quality of care for myocardial infarction (MI). Most studies focus on hospitalised case fatality, which does not capture the total burden of MI deaths. Additionally, changes in diagnostic criteria and acute clinical care, and evidence that identifying all coronary heart disease (CHD) events better captures this patient group,1 have led to suggestions that a different definition of case fatality is required. Purpose The aim of the study was to determine the impact of different definitions of case fatality on the composition of fatal cases, and to measure trends in case fatality across a range of case definitions. Methods A whole-state linked hospital/death dataset was used to identify all MI, acute coronary syndromes (ACS) and CHD events (fatal + nonfatal) from 1997-2015. The traditional MI case fatality definition included all MI deaths as the numerator, stratified as MI hospitalisation with death ≤28 days, non-MI hospitalisation with MI death ≤28 days, or pre-hospital MI deaths. The denominator was all MIs (fatal plus nonfatal MI). ACS and a broader CHD definition were trialled, with ACS or CHD deaths as the numerator respectively, stratified in a similar manner as MI. Case fatality was age-standardised by 5-year age group using the internal age distribution of each definition as the standard. Results From 1997 to 2015, there were 76,928 MI events, 126,470 ACS events, and 235,100 CHD events. Of the MI cohort, 64.1% were men, and 13.0% had a prior MI, with a similar pattern in the ACS and CHD cohorts. For the traditional definition of MI case fatality, 10,819 deaths (53.9%) occurred pre-hospital, 4990 deaths in those hospitalised for MI and dying ≤28 days (24.8%), and 4271 MI deaths (21.3%) ≤28 days of a non-MI hospitalisation (Figure). Using the broadest CHD definition of case fatality, there was a similar proportion of pre-hospital deaths, but a higher proportion of CHD deaths in those with a non-CHD hospitalisation. In men, age-standardised MI case fatality declined from 40.0% in 1997 to 17.3% by 2015; in women, the decline was from 41.9% to 18.2%. In contrast, using the ACS and broad CHD definitions, age-standardised case fatality was lower than for MI throughout the study period, with a smaller temporal decline (ACS: men 22.2% to 13.1%, women 20.5% to 13.0%; CHD: men 20.6% to 12.4%, women 19.3% to 12.3%). Conclusion Despite substantial falls in MI case fatality, the fatal burden remains high. Regardless of the case fatality definition, pre-hospital deaths from acute or all CHD have remained high over time, highlighting the need to target the pre-hospital setting. Caution is needed when using different definitions of case fatality to ensure relevant statistics are used, particularly for temporal trends. Figure Legend. Proportion of MI deaths occurring ≤28 days after MI hospitalisation (2), ≤28 days after non-MI hospitalisation (3), and pre-hospital (4).

Implementing shared decision-making in Australia

Person-centred care (PCC) and shared decision-making (SDM) are part of national clinical standards for an increasing number of areas of health care delivery. In addition to existing standards for accrediting hospitals, day surgery facilities, public dental services and medical education in Australia, new standards governing primary health care and digital mental health services have been added. Implementation and measurement of PCC and SDM to comply with standards, and training of health professionals, remain challenges for the Australian health sector. Consumer involvement in health research, policy and clinical service governance continues to increase and the National Health and Medical Research Council has begun to encourage consumer and community involvement in health and medical research. This increased consumer engagement and moves towards more PCC provision is reflected in a focus on encouraging patients to ask questions during their clinical care and supports improvements in consumer health literacy. SDM support tools are now being culturally adapted whilst a need for more systemic approaches to their development and implementation persists. With increasing resources and tools for all aspects of PCC and SDM challenges to find sustainable solutions to ensure tools are kept up to date with the best available evidence remain.

Where are we in understanding the natural history of polycystic ovary syndrome? A systematic review of longitudinal cohort studies.

STUDY QUESTIONWhat 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 ANSWERExisting 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 ALREADYThe 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, DURATIONThis 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, METHODSIn 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 CHANCEA 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 CAUTIONThere 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 FINDINGSUnderstanding 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 NUMBERProspero registration number: CRD42020165546.