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Abstract Background Knowledge of developmental trends in meeting age-specific 24-hour movement behaviour guidelines is lacking. This study describes developmental trends in device-measured physical activity and sedentary time over a three-year period among Western Australian children aged two to seven years, including differences between boys and girls. The proportion of children meeting age-specific physical activity guidelines before and after they transition to full-time school was also examined. Methods Data from waves 1 and 2 of the Play Spaces and Environments for Children’s Physical Activity (PLAYCE) cohort study were used (analysis n = 1217). Physical activity and sedentary time were measured by accelerometry at ages two to five (preschool, wave 1) and ages five to seven (commenced full-time school, wave 2). Accelerometer data were processed using a validated machine-learning physical activity classification model. Daily time spent in sedentary behaviour, energetic play (moderate-to-vigorous physical activity (MVPA)), total physical activity, and meeting physical activity guidelines were analysed using linear and generalised linear mixed-effects models with age by sex interaction terms. Results All movement behaviours changed significantly with increasing age, and trends were similar in boys and girls. Total daily physical activity increased from age two to five then declined to age seven. Mean daily total physical activity exceeded 180 min/day from ages two to five. Daily energetic play increased significantly from age two to seven, however, was below 60 min/day at all ages except for seven-year-old boys. Daily sedentary time decreased to age five then increased to age seven but remained lower than at age two. All two-year-olds met their age-specific physical activity guideline, decreasing to 5% of girls and 6% of boys at age four. At age seven, 46% of boys and 35% of girls met their age-specific physical activity guideline. Conclusions Young children’s energetic play and total physical activity increased with age, but few children aged three to seven met the energetic play (MVPA) guideline. Interventions should focus on increasing children’s energetic play in early childhood. Clearer guidance and strategies are needed to support young children as they change developmentally and as they transition from one age-specific movement guideline to the next.

Abstract Natural outdoor environments provide important settings for children to engage in physical activity. It is unclear if these relationships also exist in preschool aged children. We examined associations between amount and type of neighbourhood vegetation and blue space, proximity to the beach and preschooler's device‐measured movement behaviours. Accelerometer data from 1081 preschool children were processed into physical activity and sedentary behaviours using a machine learned random forest physical activity classification model specifically developed for children under five. High‐resolution aerial imagery data and Geographic Information Systems were used to identify total percentage of neighbourhood vegetation and vegetation components (grass, shrubs and trees) and presence and total percentage of blue space (ocean, riverways and lakes and swamps) for 500, 1600 and 5000 m service areas around children's residences. Distance to the closest beach, patrolled beach, and dog beach were also calculated. Amount of neighbourhood vegetation was inversely associated with boys sedentary time in the 500 m (β = −0.91 min/day, p = 0.006, 95% CI [−1.55, −0.33]) and 1600 m (β = −1.30 min/day, p = 0.001, 95% CI [−2.08, −0.53]) service area, and positively associated with walking time in the 1600 m (β = 0.12 min/day, p = 0.045, 95% CI [0.02, 0.22]) service area. The presence of local riverways was positively associated with girls walking time in the 1600 m (β = 2.34 min/day, p = 0.009, 95% CI [0.59, 4.09]), and 5000 m (β = 1.67 min/day, p = 0.019, 95% CI [0.27, 3.06]) buffer. Distance to dog beach was positively associated with boys sedentary behaviours. Presence of lake and swamps were negatively associated with boys walking, and presence of riverways was negatively associated with girls moderate‐to‐vigorous activities and games and boys running in the 5000 m service area. These findings suggest higher amounts of neighbourhood vegetation and certain types of blue space such as riverways and dog beaches could facilitate positive movement behaviours in young children. Our findings that natural outdoor environments are associated with preschool children's movement behaviours add to evidence which could contribute to policy implications for urban planning and the provision and protection of natural environments within cities. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Drought adaptation is critical to many tree species persisting under climate change, however our knowledge of the genetic basis for trees to adapt to drought is limited. This knowledge gap impedes our fundamental understanding of drought response and application to forest production and conservation. To improve our understanding of the genomic determinants, architecture, and trait constraints, we assembled a reference genome and detected ~ 6.5 M variants in 432 phenotyped individuals for the foundational tree Corymbia calophylla. Results We found 273 genomic variants determining traits with moderate heritability (h 2 SNP = 0.26–0.64). Significant variants were predominantly in gene regulatory elements distributed among several haplotype blocks across all chromosomes. Furthermore, traits were constrained by frequent epistatic and pleiotropic interactions. Conclusions Our results on the genetic basis for drought traits in Corymbia calophylla have several implications for the ability to adapt to climate change: (1) drought related traits are controlled by complex genomic architectures with large haplotypes, epistatic, and pleiotropic interactions; (2) the most significant variants determining drought related traits occurred in regulatory regions; and (3) models incorporating epistatic interactions increase trait predictions. Our findings indicate that despite moderate heritability drought traits are likely constrained by complex genomic architecture potentially limiting trees response to climate change.

IntroductionDietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link.ObjectiveTo investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status.MethodsThis study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study followed over a period of 17 years. Intakes of plant-sourced, vegetable-sourced, naturally occurring animal-sourced nitrate, and processed meat (where nitrate is an allowed additive)-sourced nitrate were assessed from a 74-item food frequency questionnaire completed by participants at baseline and nitrate databases were used to estimate nitrate from these different dietary sources. Associations between source-dependent nitrate intake and dementia-related mortality were assessed using multivariable-adjusted Cox proportional hazards models adjusted for demographics, lifestyle, and dietary factors.ResultsOver 17 years of follow-up, 93 (1.0%) dementia-related deaths occurred of 1,237 (13.5%) total deaths. In multivariable-adjusted models, participants with the highest intakes of plant-sourced nitrate (median intake 98 mg/day) had a 57% lower risk of dementia-related mortality [HR (95% CI): 0.43 (0.22, 0.87)] compared to participants with lowest intakes of plant-sourced nitrate (median intake 35 mg/day). A 66% lower risk was also seen for higher intakes of vegetable-sourced nitrate [HR (95% CI): 0.34 (0.17, 0.66)]. No association was observed for animal-sourced nitrate, but the risk was two times higher amongst those who consumed the most processed meat-sourced nitrate intake [HR (95%): 2.10 (1.07, 4.12)]. The highest intake of vegetable-sourced nitrate was associated with a lower risk of dementia-related mortality for those with and without DM and pre-diabetes.ConclusionEncouraging the intake of nitrate-rich vegetables, such as green leafy vegetables and beetroot, may lower the risk of dementia-related mortality, particularly in individuals with (pre-) diabetes who are at a higher dementia risk.

Abstract Background Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. Methods A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. Discussion Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. Ethics and dissemination Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Background: The clinical consequences of an antibiotic allergy label are detrimental, impacting health care delivery and patient outcomes. We assessed hospital inpatients with intent to offer free antibiotic allergy labeling (AAL) assessment within a randomized controlled trial. Objective: We sought to determine the feasibility of establishing an adult antibiotic allergy delabeling service in a Western Australian tertiary public hospital. Methods: Inpatients (N = 1503) with AAL were identified through medical records and screened for eligibility to participate in a randomized controlled trial. Those recruited were randomized to undergo assessment by skin testing ± oral challenge, or direct oral challenge. A control group received usual care. Results: Of the 1503 inpatients with an AAL, 429 (28.5%) were eligible for AAL assessment. The primary excluding factor (1074 [71.5%]) was contraindicated medication use (387 [36.0%]), followed by cognitive impairment (298 [27.9%]). Thirty-nine patients were randomized, of which 20 received allergy testing and 19 usual care; all patients were followed up for 5 years. Older patients were less likely to be eligible (10-year increase: odds ratio, 0.82; 95% CI, 0.77-0.88; P < .0001), whereas surgical patients were more likely to be eligible than medical patients (odds ratio, 2.49; 95% CI, 1.97-3.16; P < .0001). Conclusions: Antibiotic allergy delabeling in the acute care context is not straightforward. Competing clinical concerns and patient acceptance are some barriers to an inpatient service. Nor is it apparent that inpatient versus outpatient testing is cost saving although select patient groups may benefit. Testing younger people and those with predicted high antibiotic usage will derive maximal individual and health system benefits.

ABSTRACT Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our understanding of host-microbe interactions, we have developed an integrated analytical and bioinformatic mass spectrometry (MS)-based metaproteomics workflow to analyze clinical bronchoalveolar lavage (BAL) samples from people with airway disease. Proteins from BAL cellular pellets were processed and pooled together in groups categorized by disease status (CF vs. non-CF) and bacterial diversity, based on previously performed small subunit rRNA sequencing data. Proteins from each pooled sample group were digested and subjected to liquid chromatography tandem mass spectrometry (MS/MS). MS/MS spectra were matched to human and bacterial peptide sequences leveraging a bioinformatic workflow using a metagenomics-guided protein sequence database and rigorous evaluation. Label-free quantification revealed differentially abundant human peptides from proteins with known roles in CF, like neutrophil elastase and collagenase, and proteins with lesser-known roles in CF, including apolipoproteins. Differentially abundant bacterial peptides were identified from known CF pathogens (e.g., Pseudomonas), as well as other taxa with potentially novel roles in CF. We used this host-microbe peptide panel for targeted parallel-reaction monitoring validation, demonstrating for the first time an MS-based assay effective for quantifying host-microbe protein dynamics within BAL cells from individual CF patients. Our integrated bioinformatic and analytical workflow combining discovery, verification, and validation should prove useful for diverse studies to characterize microbial contributors in airway diseases. Furthermore, we describe a promising preliminary panel of differentially abundant microbe and host peptide sequences for further study as potential markers of host-microbe relationships in CF disease pathogenesis.IMPORTANCEIdentifying microbial pathogenic contributors and dysregulated human responses in airway disease, such as CF, is critical to understanding disease progression and developing more effective treatments. To this end, characterizing the proteins expressed from bacterial microbes and human host cells during disease progression can provide valuable new insights. We describe here a new method to confidently detect and monitor abundance changes of both microbe and host proteins from challenging BAL samples commonly collected from CF patients. Our method uses both state-of-the art mass spectrometry-based instrumentation to detect proteins present in these samples and customized bioinformatic software tools to analyze the data and characterize detected proteins and their association with CF. We demonstrate the use of this method to characterize microbe and host proteins from individual BAL samples, paving the way for a new approach to understand molecular contributors to CF and other diseases of the airway.

Abstract Introduction Regular physical activity is important for children’s physical and mental health, yet many children do not achieve recommended amounts of physical activity. Dog ownership has been associated with increased physical activity in children, however, there have been no longitudinal studies examining this relationship. This study used data from the Play Spaces and Environments for Children’s Physical Activity (PLAYCE) cohort study to examine the longitudinal effects of dog ownership status on children’s movement behaviours. Methods Change in dog ownership from preschool (wave 1, age 2–5) to fulltime school (wave 2, age 5–7) was used as a natural experiment with four distinct dog ownership groups: continuing non-dog owners (n = 307), continuing dog owners (n = 204), dog acquired (n = 58), and dog loss (n = 31; total n = 600). Daily movement behaviours, including physical activity, sedentary time, sleep, and screen time, were measured using accelerometry and parent-report surveys. Differences between groups over time and by sex were tested using linear mixed effects regression models. Results Girls who acquired a dog increased their light intensity activities and games by 52.0 min/day (95%CI 7.9, 96.0) and girls who lost a dog decreased their light intensity activities and games by 62.1 min/day (95%CI -119.3, -4.9) compared to no change among non-dog owners. Girls and boys who acquired a dog increased their unstructured physical activity by 6.8 (95%CI 3.2, 10.3) and 7.1 (95%CI 3.9, 10.3) occasions/week, compared to no changes among non-dog owners. Girls and boys who lost a dog reduced their unstructured physical activity by 10.2 (95%CI -15.0, -5.3) and 7.7 (95%CI -12.0, -3.5) occasions/week. Girls who lost a dog decreased their total physical activity by 46.3 min/day (95%CI -107.5, 14.8) compared to no change among non-dog owners. Continuing dog ownership was typically not associated with movement behaviours. Dog ownership group was not associated with changes in sleep and had mixed associations with screen time. Conclusion The positive influence of dog ownership on children’s physical activity begins in early childhood and differs by child sex. Further research should examine the specific contributions dog-facilitated physical activity makes to children’s overall physical activity, including the intensity and duration of dog walking and play.

During 2013–2017, the mortality rate ratio for rheumatic heart disease among Indigenous versus non-Indigenous persons in Australia was 15.9, reflecting health inequity. Using excess mortality methods, we found that deaths associated with rheumatic heart disease among Indigenous Australians were probably substantially undercounted, affecting accuracy of calculations based solely on Australian Bureau of Statistics data.

The aim of this study was to describe the implementation of a novel 50-bed continuous remote monitoring service for high-risk acute inpatients treated in non-critical wards, known as Health in a Virtual Environment (HIVE). We report the initial results, presenting the number and type of patients connected to the service, and assess key outcomes from this cohort. This was a prospective, observational study of characteristics and outcomes of patients connected to the HIVE continuous monitoring service at a major tertiary hospital and a smaller public hospital in Western Australia between January 2021 and June 2023. In the first two and a half years following implementation, 7541 patients were connected to HIVE for a total of 331,118 h. Overall, these patients had a median length of stay of 5 days (IQR 2, 10), 11.0% (n = 833) had an intensive care unit admission, 22.4% (n = 1691) had an all-cause emergency readmission within 28 days from hospital discharge, and 2.2% (n = 167) died in hospital. Conclusions: Our initial results show promise, demonstrating that this innovative approach to inpatient care can be successfully implemented to monitor high-risk patients in medical and surgical wards. Future studies will investigate the effectiveness of the program by comparing patients receiving HIVE supported care to comparable patients receiving routine care.

Background Cardiovascular disease is the most common cause of death in people with gout. Acute inflammation, which is a characteristic of gout, may have a mechanistic role in major adverse cardiovascular events (MACEs). We aimed to examine the relationship between admissions to a hospital with acute gout and MACEs in a large population‐based data set. Methods We extracted data from the Hospital Morbidity Data Collection and Death Registrations of the Western Australian Rheumatic Disease Epidemiology Registry. We identified patients admitted to hospital with incident acute gout and who had admissions or a death record because of MACEs. We compared the risk of MACEs during the postdischarge period (1‐30 days after acute gout admission) and control period (365 days prior to admission and 365 days after the postdischarge period) using a self‐controlled case‐series (SCCS) design, which is a within‐person design that controls for time‐invariant patient‐specific confounding. We performed conditional fixed‐effects Poisson regression to obtain rate ratios (RRs). Results We identified 941 patients (average age: 76.4 years; SD: 12.6; 66.7% male) with an incident acute gout admission and documented MACEs during the control and/or postdischarge periods. Of the 941 patients, 898 (95%) experienced MACEs during the combined control period (730‐day period) and 112 (12%) during the postdischarge period (30‐day period). The rates of MACEs during the total control and postdischarge periods were 0.84 and 1.45 events per person‐year, respectively. Regression analysis confirmed increased rate during the postdischarge period (RR: 1.67; 95% CI: 1.38‐2.03) compared with the control period. Sensitivity analyses indicated that our results were robust in relation to known limitations of the SCCS design. Conclusion We report an increased risk of MACEs in the first 30 days after an incident hospital admission with acute gout, suggesting a temporal association between acute inflammation and subsequent MACEs in patients with gout.

IntroductionEvidence of the benefits of arts engagement to community wellbeing has been mounting since the 1990s. However, large scale, quantitative, epidemiological studies of the “arts–healthy aging” relationship, or the types of arts older adults voluntarily choose to engage in as part of their everyday life, for enjoyment, entertainment or as a hobby (vs. therapy or interventions) are limited. The aims of this study were to describe older adult recreational arts engagement via the Busselton Healthy Ageing Study (BHAS) cohort, and to determine if there was an association between arts engagement, general health and mental wellbeing.MethodsOverall, 2,843 older adults (born 1946–1964) from the BHAS cohort (n = 5,107) who had completed a supplementary arts survey (n = 3,055, 60%) and had data on required variables were included in this study (93% of those eligible). The dependent variable was general health (SF12) and subjective mental wellbeing (Warwick-Edinburgh Mental Wellbeing Scale, WEMWBS). The independent variable was hours engaged in recreational arts in the last 12 months. A descriptive analysis followed by a linear regression analysis was conducted.ResultsThe prevalence of recreational arts engagement in the last 12 months was 85% (mean = 132 h/year). Older adults engaged in the arts in a number of ways including attending events (79%), actively participating/making art (40%), as an arts society/club/organization member (20%), by learning about the arts (13%) or by volunteering/working in the arts (non-professional, 11%). When general health was assessed via the SF12, the average physical component score (PCS) was 50.1 (SD 8.9) and the average mental component score (MCS) was 53.6 (SD 8.3). When mental wellbeing was assessed, the average WEMWBS score was 54.9 (SD = 8.6). After adjustment for 12 demographic and lifestyle covariates, it was found that older adults who engaged in any recreational arts in the last 12 months had significantly higher WEMWBS scores and higher SF12 physical component scores than those who did not engage in the arts (0 h/year).DiscussionEvidence of an arts-health relationship was found in this study. The suitability of the arts as a population based, healthy aging strategy to influence the mental wellbeing and general health of older adults should be investigated further.

Background: Food allergy affects up to 10% of Australian infants. It was hypothesized that if parents follow the Australasian Society of Clinical Immunology and Allergy guidelines, Australian food allergy rates may stabilize or decline. Objective: This project aimed to determine whether SmartStartAllergy influenced parental introduction of peanut by age 12 months, including in high-risk infants. Methods: SmartStartAllergy integrates with general practice management software to send text messages to parents via participating general practices. The intervention group participants were sent text messages when their child was aged 6, 9, and 12 months; the control group participants were parents of 12-month-old infants. When their child was aged 12 months, all participants completed a questionnaire regarding eczema and family history of atopy. Infants with severe eczema and/or a family history of atopy were considered high-risk. Results: Between 21 September 2018 and 26 April 2022, a total of 29,092 parents were enrolled in SmartStartAllergy as intervention (n = 18,090) and control (n = 11,002) group members The intervention group was more likely to introduce peanut by 12 months (crude odds ratio = 5.18; P < .0001; 95% CI = 4.35-6.16). After adjustment for the infants’ level of risk and family history of atopy and food allergy, the intervention group was more likely to introduce peanut by 12 months of age (adjusted odds ratio = 5.34; P < .01; 95% CI = 4.48-6.37). Conclusion: SmartStartAllergy appears to be an effective tool for encouraging parental introduction of peanut. The ability to provide parents with credible allergy prevention information, along with the capacity to collect simple responses via text along with additional information via an online questionnaire, make this a useful public health tool.

Abstract Background Readmissions within 30 days after heart failure (HF) hospitalisation is considered an important healthcare quality metric, but their impact on medium-term mortality is unclear within an Australian setting. We determined the frequency, risk predictors and relative mortality risk of 30-day unplanned readmission in patients following an incident HF hospitalisation. Methods From the Western Australian Hospitalisation Morbidity Data Collection we identified patients aged 25–94 years with an incident (first-ever) HF hospitalisation as a principal diagnosis between 2001 and 2015, and who survived to 30-days post discharge. Unplanned 30-day readmissions were categorised by principal diagnosis. Logistic and Cox regression analysis determined the independent predictors of unplanned readmissions in 30-day survivors and the multivariable-adjusted hazard ratio (HR) of readmission on mortality within the subsequent year. Results The cohort comprised 18,241 patients, mean age 74.3 ± 13.6 (SD) years, 53.5% males, and one-third had a modified Charlson Comorbidity Index score of ≥ 3. Among 30-day survivors, 15.5% experienced one or more unplanned 30-day readmission, of which 53.9% were due to cardiovascular causes; predominantly HF (31.4%). The unadjusted 1-year mortality was 15.9%, and the adjusted mortality HR in patients with 1 and ≥ 2 cardiovascular or non-cardiovascular readmissions (versus none) was 1.96 (95% confidence interval (CI) 1.80–2.14) and 3.04 (95% CI, 2.51–3.68) respectively. Coexistent comorbidities, including ischaemic heart disease/myocardial infarction, peripheral arterial disease, pneumonia, chronic kidney disease, and anaemia, were independent predictors of both 30-day unplanned readmission and 1-year mortality. Conclusion Unplanned 30-day readmissions and medium-term mortality remain high among patients who survived to 30 days after incident HF hospitalisation. Any cardiovascular or non-cardiovascular readmission was associated with a two to three-fold higher adjusted HR for death over the following year, and various coexistent comorbidities were important associates of readmission and mortality risk. Our findings support the need to optimize multidisciplinary HF and multimorbidity management to potentially reduce repeat hospitalisation and improve survival.

Background: Survival during the early period following myocardial infarction (MI) has significantly improved although there are limited data on cardiovascular recurrence during this period. Methods: We identified all emergency hospitalisations for MI from November 1, 2011 to October 31, 2016 in Western Australia from a linked hospitalisation/mortality dataset. Patients were included if they survived >3 days, had no acute kidney injury, and had ≥1 of: ≥65 years, prior MI, diabetes or peripheral arterial disease. Outcomes were major adverse cardiovascular events (MACE, a composite of CVD death, recurrent MI or stroke), cardiovascular disease (CVD) death, all-cause mortality, recurrent MI and stroke. Cumulative risks at 90-days and 1-year were estimated from Kaplan-Meier analyses and predictors of each outcome from multivariable Cox regression models. Results: There were 8024 high-risk MI patients identified (males 61.8%). Median age was 73.7 years (IQR 66.3–82.2). Half of the risk of MACE occurred in the first 90-days post-MI (6.6% vs 12.6% at 1-year) and was underpinned by risk of recurrent MI. Risk was generally higher in women than men (MACE: 6.0% males, 7.7% females, p = 0.0025; CVD mortality: 1.7% males, 3.7% females; all-cause mortality: 2.8% males, 5.6% females, p

Abstract Introduction Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. Methods and analysis A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. Ethics and dissemination Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. Discussion Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. Trial registration Australia New Zealand Clinical Trial Registry ACTRN12618001013257 . Registered on 18 June 2018. Protocol version: Version 3.00/4.02.19

Abstract Background Population health behaviour and risk factor surveys most often rely on self-report but there is a lack of studies assessing the validity of self-report using Australian data. This study investigates the sensitivity, specificity and agreement of self-reported hypertension and hypercholesterolaemia with objective measures at standard and more stringent diagnostic thresholds; and factors associated with sensitivity and specificity of self-report at different thresholds. Methods This study was a secondary analysis of a representative community-based cross-sectional sample of 5,092 adults, aged 45–69 years, residing in Busselton, Western Australia, surveyed in 2010–2015. Participants completed a self-administered questionnaire. Blood pressure and serum cholesterol levels were measured. Results At currently accepted diagnostic thresholds, sensitivities of self-reported hypertension and hypercholesterolaemia were 58.5% and 39.6%, respectively and specificities were >90% for both. Agreement using Cohen’s kappa coefficient was 0.562 and 0.223, respectively. At two higher diagnostic thresholds, sensitivities of self-reported hypertension and hypercholesterolaemia improved by an absolute 14–23% and 15–25%, respectively and specificities remained >85%. Agreement was substantial for hypertension (kappa = 0.682–0.717) and moderate for hypercholesterolaemia (kappa = 0.458–0.533). Variables that were independently associated with higher sensitivity and lower specificity of self-report were largely consistent across thresholds and included increasing age, body mass index, worse self-rated health, diabetes and family history of hypertension. Conclusions Self-reported hypertension and hypercholesterolaemia often misclassify individuals’ objective status and underestimate objective prevalences, at standard diagnostic thresholds, which has implications for surveillance studies that rely on self-reported data. Self-reports of hypertension, however, may be reasonable indicators of those with blood pressures ≥160/100 mmHg or those taking anti-hypertensive medications. Self-reported hypercholesterolaemia data should be used with caution at all thresholds.

Abstract Background and objective Chronic medical conditions accumulate within individuals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive individual phenotyping in a general population of Australian middle-aged adults. Methods Participants (n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated. Results The individual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0–13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence > 1.5% and O/E > 1.5. Of the triplets, arthritis (> 50%), bowel disease (> 33%) and depression-anxiety (> 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) “Healthy” (70%) with average of 1.95 conditions; 2) “Respiratory and Atopy” (11%, 3.65 conditions); 3) “Non-cardiometabolic” (14%, 4.77 conditions), and 4) “Cardiometabolic” (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions. Conclusion Multimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in individuals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.

Introduction Childhood obesity and physical inactivity are two of the most significant modifiable risk factors for the prevention of non-communicable diseases (NCDs). Yet, a third of children in Wales and Australia are overweight or obese, and only 20% of UK and Australian children are sufficiently active. The purpose of the Built Environments And Child Health in WalEs and AuStralia (BEACHES) study is to identify and understand how complex and interacting factors in the built environment influence modifiable risk factors for NCDs across childhood.Methods and analysis This is an observational study using data from five established cohorts from Wales and Australia: (1) Wales Electronic Cohort for Children; (2) Millennium Cohort Study; (3) PLAY Spaces and Environments for Children’s Physical Activity study; (4) The ORIGINS Project; and (5) Growing Up in Australia: the Longitudinal Study of Australian Children. The study will incorporate a comprehensive suite of longitudinal quantitative data (surveys, anthropometry, accelerometry, and Geographic Information Systems data) to understand how the built environment influences children’s modifiable risk factors for NCDs (body mass index, physical activity, sedentary behaviour and diet).Ethics and dissemination This study has received the following approvals: University of Western Australia Human Research Ethics Committee (2020/ET000353), Ramsay Human Research Ethics Committee (under review) and Swansea University Information Governance Review Panel (Project ID: 1001). Findings will be reported to the following: (1) funding bodies, research institutes and hospitals supporting the BEACHES project; (2) parents and children; (3) school management teams; (4) existing and new industry partner networks; (5) federal, state and local governments to inform policy; as well as (6) presented at local, national and international conferences; and (7) disseminated by peer-reviewed publications.

Objectives Cardiovascular disease is the largest contributor of increased mortality in patients with gout. Acute inflammation as seen with gout attacks may have a mechanistic role in developing Major Adverse Cardiovascular Events (MACE). We examined the temporal relationship between admission to hospital with acute gout and MACE. Approach Linked inpatient and mortality data from the Western Australian Rheumatic Disease Epidemiology Registry were used. We identified patients with an incident acute gout (index) hospitalisation and admission or death records due to MACE (composite of acute coronary syndrome, stroke, heart failure, cardiovascular death). The risk of MACE during the index post-discharge period (1-30 days after index admission) and control period (365 days prior to index admission and 365 days post-discharge) was determined using a self-controlled case-series (SCCS) design. Conditional fixed-effects Poisson regression was used to obtain incidence rate ratios (IRR). Sensitivity analyses were performed excluding deaths and 180-day events. Results We identified 962 patients (mean age=76.2 years [SD=12.2]; 66.8% male) with incident acute gout admission and documented MACE during the control and/or index post-discharge periods. 917 (95.3%) patients experienced MACE during the control period and 114 (11.9%) during the index post-discharge period. The rate of MACE during the control and post-discharge periods were 0.84 and 1.44 events per person-year, respectively, with an IRR=1.67 (95% CI: 1.38-2.02) for the post-discharge period compared with the control period from regression analysis. Sensitivity analyses excluding deaths and 180-day events were IRR=1.68 (95% CI=1.29-2.20) and IRR=1.66 (95% CI=1.34-2.07) respectively. Conclusion Our self-controlled case-series study using linked administrative data found an increased risk of MACE during the 30 days after discharge for index gout hospitalisation. This suggests a temporal association between acute inflammation and MACE.

24-hour Movement Guidelines for the Early Years promote that achieving all three-movement behaviour (sleep, sedentary behaviour and physical activity) recommendations is important for child health and development. We examined the association between meeting all, none and combinations of the Australian 24-Hour Movement Guidelines for the Early Years and social-emotional development in 1363 preschool (2–5 years) boys (52%) and girls. The PLAYCE study (Perth, Western Australia) parent survey collected data on children’s social-emotional development (Strengths & Difficulties Questionnaire), screen time, sleep and socio-demographic factors. Physical activity was measured using seven-day accelerometry. Only 8% of preschoolers met all three guidelines (5% met none). A higher proportion of boys than girls met physical activity-related guideline combinations (physical activity only, physical activity plus screen, physical activity plus sleep, all), while more girls than boys met sleep only guidelines (all p

Fatty acids are the building blocks of the entire human milk lipidome; yet, despite years of research, there is little understanding of their importance in early life health and disease. This may be partly due to the way in measurements have been made of fatty acids in the past. Monthly longitudinal human milk samples were collected from eighteen Western Australian mother–infant dyads, during six months of exclusive breastfeeding (n = 704). Additionally, data including monthly anthropometric measurements, health information, and basic maternal food frequency questionnaires were also collected. Infant 24 h milk intake and total lipid intake were measured at three months. Gas chromatography-mass spectrometry was used to profile human milk fatty acids. Linear regression and Pearson’s correlation were used to identify associations between human milk fatty acid composition, intake, maternal characteristics, and infant outcomes. Significant variation in human milk fatty acid composition was identified between dyads, and throughout lactation. Mean infant intake for total lipids was 29.7 ± 9.4 g/day. Intake of many fatty acids, including long chain fatty acids, such as C15:0, C18:1, and C18:2, were positively associated with infant growth (p < 0.001). This study identified important findings for many human milk fatty acids not previously described, including C15:0 and C18:2 species. Infant total lipid intake and fatty acid intake perform essential roles in infant growth and development. This study highlights the importance of human milk sampling, analytical methods, and estimating infant intake in relation to infant outcomes. Indeed, these factors should be carefully considered in future research.

Abstract Rationale Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium. Methods and design The ‘Prophylactic Melatonin for Delirium in Intensive Care’ study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium. Results This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications. Discussion The SAP details the analyses that will be done to avoid bias coming from knowledge of the results in advance. This trial will determine whether prophylactic melatonin administered to intensive care unit patients helps decrease the rate and the severity of delirium. Trial registration Australian and New Zealand Clinical Trial Registry (ANZCTR) ACTRN1261600043647 , registration date: 06 April 2016. WHO Trial Number – U1111-1175-1814

Abstract Background In disease mapping, fine-resolution spatial health data are routinely aggregated for various reasons, for example to protect privacy. Usually, such aggregation occurs only once, resulting in ‘single-aggregation disease maps’ whose representation of the underlying data depends on the chosen set of aggregation units. This dependence is described by the modifiable areal unit problem (MAUP). Despite an extensive literature, in practice, the MAUP is rarely acknowledged, including in disease mapping. Further, despite single-aggregation disease maps being widely relied upon to guide distribution of healthcare resources, potential inefficiencies arising due to the impact of the MAUP on such maps have not previously been investigated. Results We introduce the overlay aggregation method (OAM) for disease mapping. This method avoids dependence on any single set of aggregate-level mapping units through incorporating information from many different sets. We characterise OAM as a novel smoothing technique and show how its use results in potentially dramatic improvements in resource allocation efficiency over single-aggregation maps. We demonstrate these findings in a simulation context and through applying OAM to a real-world dataset: ischaemic stroke hospital admissions in Perth, Western Australia, in 2016. Conclusions The ongoing, widespread lack of acknowledgement of the MAUP in disease mapping suggests that unawareness of its impact is extensive or that impact is underestimated. Routine implementation of OAM can help avoid resource allocation inefficiencies associated with this phenomenon. Our findings have immediate worldwide implications wherever single-aggregation disease maps are used to guide health policy planning and service delivery.

Abstract Background Concerns about reduced milk transfer with nipple shield (NS) use are based on evidence from studies with methodological flaws. Milk removal during breastfeeding can be impacted by infant and maternal factors other than NS use. The aim of this study was to control electric breast pump vacuum strength, pattern and duration across multiple study sessions to determine if NS use reduces milk removal from the breast. Methods A within-subject study with two groups of breastfeeding mothers (infants

Abstract Background There are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality. Methods This was a systematic review of systematic reviews (overview). We searched MEDLINE, Embase, Web of Science Core Collection, PubMed, Google Scholar, and the Joanna Briggs Institute EBP Database, from 2008 to 2018. We included systematic reviews and meta-analyses of randomised controlled trials comparing mortality in patients assigned to red cell transfusion strategies based on haemoglobin thresholds. Two independent reviewers extracted data and assessed methodological quality. We assessed the methodological quality of included reviews using AMSTAR 2 and the quality of evidence pooled using an algorithm to assign GRADE levels. Results We included 19 systematic reviews reporting 33 meta-analyses of mortality outcomes from 53 unique randomised controlled trials. Of the 33 meta-analyses, one was graded as high quality, 15 were moderate, and 17 were low. Of the meta-analyses presenting high- to moderate-quality evidence, 12 (75.0%) reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and four (25.0%) reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. We found few systematic reviews addressed clinical differences between included studies: variation was observed in haemoglobin threshold concentrations, the absolute between group difference in haemoglobin threshold concentration, time to randomisation (resulting in transfusions administered prior to randomisation), and transfusion dosing regimens. Conclusions Meta-analyses graded as high to moderate quality indicate that in most patient populations no difference in mortality exists between patients assigned to a restrictive or liberal transfusion strategy. Trial registration PROSPERO CRD42019120503

The assessment of dietary patterns comprehensively represents the totality of the diet, an important risk factor for many chronic diseases. This study aimed to characterise and compare four dietary pattern indices in middle-aged Australian adults. In 3458 participants (55% female) from the Busselton Healthy Ageing Study (Phase Two), a validated food frequency questionnaire was used to capture dietary data between 2016 and 2022. Four dietary patterns [Australian Dietary Guideline Index 2013 (DGI-2013); the Mediterranean Diet Index (MedDiet); the Literature-based Mediterranean Diet Index (Lit-MedDiet); and the EAT-Lancet Index], were calculated and compared by measuring total and sub-component scores, and concordance (𝜌c). Cross-sectional associations between the dietary indices and demographic, lifestyle, and medical conditions were modelled with linear regression and restricted cubic splines. Participants had the highest standardised scores for the DGI-2013 followed by the EAT-Lancet Index and the MedDiet, with the lowest standardised scores observed for the Lit-MedDiet. The DGI-2013 had the lowest agreement with the other scores (𝜌c ≤ 0.47). These findings indicate that the diets included in this Australian cohort align more closely with the Australian Dietary Guidelines than with the other international dietary patterns, likely due to the wide variation of individual food group weightings in the construction of these indices.

Simulation outputs from chemical transport models (CTMs) are essential to plan effective air quality policies. A key strength of these models is their ability to separate out source-specific components which facilitate the simulation of the potential impact of policy on future air quality. However, configuring and running these models is complex and computationally intensive, making the evaluation of multiple scenarios less accessible to many researchers and policy experts. The aim of this work is to present how Gaussian process emulation can provide a top-down approach to interrogating and interpreting the outputs from CTMs at minimal computational cost. A case study is presented (based on fine particle sources in the southwest of Western Australia) to illustrate how an emulator can be constructed to simultaneously evaluate changes in emissions from on-road transport and electricity sectors. This study demonstrates how emulation provides a flexible way of exploring local impacts of electric vehicles and wider regional effects of emissions from electricity generation. The potential for emulators to be applied to other settings involving air quality research is discussed.

Four COVID-19 vaccines are approved for use in Australia: Pfizer-BioNTech BNT162b2 (Comirnaty), AstraZeneca ChAdOx1 (Vaxzevria), Moderna mRNA-1273 (Spikevax) and Novavax NVX-CoV2373 (Nuvaxovid). We sought to examine adverse events following immunisation (AEFI) at days 3 and 42 after primary doses 1, 2, 3 and booster. We conducted active vaccine safety surveillance from 130 community pharmacies in Australia integrated with AusVaxSafety, between August 2021–April 2022. Main outcomes: AEFI at 0–3 days post-vaccination; medical review/advice at 3 days and 42 days post-vaccination; SARS-CoV-2 breakthrough infection by day 42. Of 110,024 completed day 3 surveys (43.6% response rate), 50,367 (45.8%) reported any AEFI (highest proportions: Pfizer 42%, primary dose 3; AstraZeneca 58.3%, primary dose 1; Moderna 65.4% and Novavax 58.8%, both primary dose 2). The most common AEFI reported across all doses/vaccines were local reactions, systemic aches and fatigue/tiredness. Overall, 2172/110,024 (2.0%) and 1182/55,329 (2.1%) respondents sought medical review at days 3 and 42, respectively, and 931/42,318 (2.2%) reported breakthrough SARS-CoV-2 infection at day 42. We identified similar AEFI profiles but at lower proportions than previously reported for Pfizer, AstraZeneca, Moderna and Novavax COVID-19 vaccines. Moderna vaccine was the most reactogenic and associated with higher AEFI proportions across primary doses 2, 3, and booster.

Background Dietary vitamin K (K1 and K2) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. Methods and Results In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food‐frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K1 and vitamin K2 were estimated from the food‐frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52–60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17–22) years of follow‐up. Compared with participants with the lowest vitamin K1 intakes, participants with the highest intakes had a 21% lower risk of an ASCVD‐related hospitalization (hazard ratio, 0.79; 95% CI: 0.74–0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K2, the risk of an ASCVD‐related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K2 intake (hazard ratio, 0.86; 95% CI, 0.81–0.91). Conclusions Risk of ASCVD was inversely associated with diets high in vitamin K1 or K2. The similar inverse associations with both vitamin K1 and K2, despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.

Food allergy is a significant issue worldwide, particularly in Westernised countries. There is no clear explanation why food allergy appears to have increased so rapidly in recent years, particularly in young children, hence ongoing research to identify effective primary prevention strategies. Food allergy prevention guidelines for health professionals have been developed based on existing clinical trial evidence for effective translation and implementation. As these guidelines underpin clinical practice, it is important to ensure robust processes of development. We conducted a systematic review to identify food allergy prevention guidelines for health professional use; to compare the recommendations made by the identified guideline documents; and to assess the quality of the identified guideline documents.We searched Medline, EMBASE, CINAHL, Scopus, Global Health and Guidelines International Network for the period 1990 to 13 August 2019, to identify articles referring to English-language food allergy prevention guidelines or the guidelines themselves. A grey literature search of Google Scholar and reference checking was also undertaken. The guidelines were compared for recommendation similarities and differences. An Appraisal Guidelines for Research and Evaluation (AGREE II) appraisal was undertaken to assess guideline quality.The electronic database search yielded 1121 publications and reference checking identified an additional 16 publications. After title, abstract and full text screening, data extraction was undertaken on 156 publications and with additional reference checking, 28 food allergy prevention guidelines and advice documents were identified. Comparison of the recommendations within the guidelines and advice documents indicated the greatest variation in recommendations related to exclusive breastfeeding and timing of solid food introduction. Eight of the 10 guidelines and none of the 18 advice documents met the quality threshold set by the reviewers. Overall, documents specifically termed ''guidelines'' scored better than advice documents when assessed using the AGREE II tool.Variation in recommendations may create confusion for health professionals and result in inconsistent advice being provided to parents, and less translation of the evidence into actual food allergy reduction in the population. Appraisal using the AGREE II tool identified that there is considerable room for improvement in the development of guidelines and advice documents for food allergy prevention. The AGREE II appraisal identified common areas of poorer quality development and/or documentation of processes to inform future guideline development. Based on this study, we recommend the use of validated guideline development tools, to direct food allergy prevention guideline review or development. Use of the AGREE II tool, to direct the review and development of guidelines, is very likely to improve guideline quality.

Objectives We integrated an established participant-centred active vaccine safety surveillance system with a cloud-based pharmacy immunisation-recording program in order to measure adverse events following immunisation (AEFI) reported via the new surveillance system in pharmacies, compared with AEFI reported via an existing surveillance system in non-pharmacy sites (general practice and other clinics).Design A prospective cohort study.Participants and setting Individuals >10 years receiving influenza immunisations from 22 pharmacies and 90 non-pharmacy (general practice and other clinic) sites between March and October 2020 in Western Australia. Active vaccine safety surveillance was conducted using short message service and smartphone technology, via an opt-out system.Outcome measures Multivariable logistic regression was used to assess the primary outcome: differences in proportions of AEFI between participants immunised in pharmacies compared with non-pharmacy sites, adjusting for confounders of age, sex and influenza vaccine brand. A subgroup analysis of participants over 65 years was also performed.Results Of 101 440 participants (6992 from pharmacies; 94 448 from non-pharmacy sites), 77 498 (76.4%) responded; 96.1% (n=74 448) within 24 hours. Overall, 4.8% (n=247) pharmacy participants reported any AEFI, compared with 6% (n=4356) non-pharmacy participants (adjusted OR: 0.87; 95% CI: 0.76 to 0.99; p=0.039). Similar proportions of AEFIs were reported in pharmacy (5.8%; n=31) and non-pharmacy participants (6; n=1617) aged over 65 years (adjusted OR: 0.94; 95% CI: 0.65 to 1.35; p=0.725). The most common AEFIs in pharmacy were: pain (2%; n=104), tiredness (1.9%; n=95) and headache (1.7%; n=88); and in non-pharmacy sites: pain (2.3%; n=1660), tiredness (1.9%; n=1362) and swelling (1.5%; n=1121).Conclusions High and rapid response rates demonstrate good participant engagement with active surveillance in both pharmacy and non-pharmacy participants. Significantly fewer AEFIs reported after pharmacist immunisations compared with non-pharmacy immunisations, with no difference in older adults, may suggest different cohorts attend pharmacy versus non-pharmacy immunisers. The integrated pharmacy system is rapidly scalable across Australia with global potential.

The studies showing health benefits of flavonoids and their impact on cancer mortality are incomplete. Here, the authors perform a prospective cohort study in Danish participants and demonstrate an inverse association between regular flavonoid intake and both cardiovascular and cancer related mortality.

Abstract Background Rapid effective responsiveness to patient needs is pivotal to high quality palliative care. Aboriginal and Torres Strait Islander (Indigenous) people are susceptible to life-limiting illnesses at younger ages than other Australians and experience inequity of health service provision. The Palliative Care Outcomes Collaboration collects Australia-wide health service data on patient care, and has established performance benchmarks for specialist palliative care services. We investigated whether the benchmark for timely commencement of palliative care episodes (occurrence of delay >1 day after being designated ‘ready for care’ in

Objectives Anticipation and prompt relief of symptoms among patients with a life-limiting illness is a core element of palliative care. Indigenous Australians commonly encounter cultural barriers in healthcare that may impair outcomes. The Palliative Care Outcomes Collaboration collects patient care data for the purposes of continuous quality improvement and benchmarking, with each recorded care episode divided into phases that reflect a patient’s condition. We aimed to investigate differences between Indigenous and non-Indigenous patients in the occurrence and duration of ‘unstable’ phases (which indicate unanticipated deterioration in a patient’s condition or circumstances), and determine attainment of the relevant benchmark (resolution of unstable phases in ≤3 days in 90% of cases) for both groups.Design Cohort study.Setting Australia-wide hospital-based and community-based specialist palliative care (1 January 2010 to 30 June 2015).Participants 139 556 (1502 Indigenous and 138 054 non-Indigenous) adult patients.Outcome measures Indigenous and non-Indigenous patients were compared on (1) the risk of a phase being categorised as unstable, (2) the duration of unstable phases, and (3) the risk of unstable phases being prolonged (>3 days). Crude and adjusted estimates were produced from three-level robust Poisson regression and complementary log-log discrete time survival models.Results Unstable phases occurred with similar frequency overall among Indigenous and non-Indigenous patients (adjusted relative risks 1.06; 95% CI 1.00 to 1.11; not significant after correction for multiple comparisons). The duration and risk of prolongation of unstable phases were similar in both patient groups, with no significant differences evident among subgroups. The benchmark was not met for either Indigenous or non-Indigenous patients (unstable phase duration >3 days in 24.3% vs 25.5%; p=0.398).Conclusions Despite well-documented shortcomings of healthcare for Indigenous Australians, there is no clear evidence of greater occurrence or prolongation of unanticipated problems among Indigenous patients accessing specialist palliative care services in hospital or the community.

While there is clear evidence that high levels of pollution are associated with increased all-cause mortality and cardiovascular mortality and morbidity, the biological mechanisms that would explain this association are less understood. We examined the association between long-term exposure to air pollutants and risk factors associated with cardiovascular disease. Air pollutant concentrations were estimated at place of residence for cohort members in the Western Australian Centre for Health and Ageing Health in Men Study. Blood samples and blood pressure measures were taken for a cohort of 4249 men aged 70 years and above between 2001 and 2004. We examined the association between 1-year average pollutant concentrations with blood pressure, cholesterol, triglycerides, C-reactive protein, and total homocysteine. Linear regression analyses were carried out, with adjustment for confounding, as well as an assessment of potential effect modification. The four pollutants examined were fine particulate matter, black carbon (BC), nitrogen dioxide, and nitrogen oxides. We found that a 2.25 μg/m3 higher exposure to fine particulate matter was associated with a 1.1 percent lower high-density cholesterol (95% confidence interval: -2.4 to 0.1) and 4.0 percent higher serum triglycerides (95% confidence interval: 1.5 to 6.6). Effect modification of these associations by diabetes history was apparent. We found no evidence of an association between any of the remaining risk factors or biomarkers with measures of outdoor air pollution. These findings indicate that long-term PM2.5 exposure is associated with elevated serum triglycerides and decreased HDL cholesterol. This requires further investigation to determine the reasons for this association.

Abstract Introduction Prospective studies investigating flavonoid intake and dementia risk are scarce. The aims of this study were to examine associations between flavonoid intake and the risk of incident dementia and to investigate whether this association differs in the presence of lifestyle risk factors for dementia. Methods We examined associations in 55,985 participants of the Danish Diet, Cancer, and Health Study followed for 23 years. The Phenol‐Explorer database was used to estimate flavonoid intakes. Information on incident dementia and dementia subtypes was obtained using Danish patient and prescription registries. Hazard ratios (HRs) were calculated using restricted cubic splines in multivariable‐adjusted Cox proportional hazards models. Results For incident dementia, moderate compared to low intakes of flavonols (HR: 0.90 [0.82, 0.99]), flavanol oligo+polymers (HR: 0.87 [0.79, 0.96]), anthocyanins (HR: 0.84 [0.76, 0.93]), flavanones (HR: 0.89 [0.80, 0.99]), and flavones (HR: 0.85 [0.77, 0.95]) were associated with a lower risk. For vascular dementia, moderate intakes of flavonols (HR: 0.69 [0.53, 0.89]) and flavanol oligo + polymers (HR: 0.65 [0.51, 0.83]) were associated with lower risk. Flavonoid intakes were not significantly associated with Alzheimer's disease or unspecified dementia. The inverse association between total flavonoid intake and incident dementia was stronger in “ever” smokers than in “never” smokers and in those without hypercholesterolemia versus those with hypercholesteremia. Furthermore, the inverse association of vascular dementia with a moderate total flavonoid intake was stronger in “ever” smokers and those who were “normal” to “overweight” versus “never” smokers or those who were “obese,” respectively. Conclusion A moderate intake of flavonoid‐rich foods may help to reduce dementia risk.

Background: Anaphylaxis events are increasing worldwide, based on studies of single administrative datasets including hospital admissions, emergency room presentations, and prescription and medical claims data. Linking multiple administrative datasets may provide better epidemiological estimates, by capturing a greater number of anaphylaxis events occurring at the individual level. In this linked data study in Western Australia, we combined 4 population-based datasets to identify anaphylaxis events, factors influencing occurrence, and change in event rates from 2002 to 2013. Methods: Four linked administrative datasets from the Western Australian Data Linkage System were used, representing ambulance attendances, emergency department presentations, hospital inpatient admissions and death registrations. An anaphylaxis cohort was identified using ICD-9-CM, ICD-10-AM and additional anaphylaxis diagnosis codes, with event rates calculated. We explored the impact of age, gender, cause, Indigenous status and socioeconomic index on event rates. Standard Poisson regression models were used to examine the significance of the change in anaphylaxis event rates over time. Results: A total 12,637 individuals (mean age 31.8 years, 49.6% female) experienced 15,462 anaphylaxis events between 2002 and 2013 (97.5% in non-Indigenous patients and 59.5% residing in the area of greatest socioeconomic advantage). Anaphylaxis event rates increased from 15.4 to 82.5/105 population between 2002 and 2013. The greatest increase in anaphylaxis events was seen in those coded as unspecified anaphylaxis (all ages, males and females combined, p

We investigated associations between intakes of human milk (HM) components (macronutrients and biologically active molecules) and regional fat depots development in healthy term infants (n = 20) across the first year of lactation. Infant limb (mid-arm and mid-thigh) lean and fat areas were assessed by ultrasound imaging at 2, 5, 9 and 12 months of age. Concentrations of HM total protein, whey protein, casein, adiponectin, leptin, lysozyme, lactoferrin, secretory IGA, total carbohydrates, lactose, HM oligosaccharides (total HMO, calculated) and infant 24-h milk intake were measured, and infant calculated daily intakes (CDI) of HM components were determined. This pilot study shows higher 24-h milk intake was associated with a larger mid-arm fat area (p = 0.024), higher breastfeeding frequency was associated with larger mid-arm (p = 0.008) and mid-thigh (p < 0.001) fat areas. Lysozyme (p = 0.001) and HMO CDI (p = 0.004) were time-dependently associated with the mid-arm fat area. Intakes of HM components and breastfeeding parameters may modulate infant limb fat depots development during the first year of age and potentially promote favorable developmental programming of infant body composition; however, further studies are needed to confirm these findings.

IntroductionPulmonary rehabilitation is a core component of the treatment of people with chronic obstructive pulmonary disease (COPD); however, the benefits gained diminish in the ensuing months. The optimal strategy for maintaining the benefits is unclear with weekly supervised maintenance exercise programmes proposed as one strategy. However, the long-term future of maintenance programs is dependent on quality evidence.Methods and analysisThe ComEx3 randomised controlled trial will investigate the efficacy of extending a weekly supervised maintenance programme for an additional 6 months following an initial 10-week maintenance programme (intervention) by comparing with a control group who receive the same 10-week maintenance programme followed by 6 months of usual care. 120 participants with COPD will be recruited. Primary objective is to determine health-related quality of life over 12 months. Secondary objectives are to determine functional exercise capacity trajectory and to perform an economic evaluation of the intervention to the health system. Outcomes will be analysed for superiority according to intention-to-treat and per-protocol approaches.Ethics and disseminationApproval has been received from the relevant ethics committees. Findings will be disseminated in peer-reviewed journals and conferences, targeting those involved in managing people with COPD as well as those who develop policies and guidelines.Clinical trial registrationANZCTR 12618000933257

Abstract The safety and efficacy of elosulfase alfa were evaluated in a multicenter, open-label, phase 3b study in Australian Morquio A patients, consisting of a 49-week initial phase and an extension phase until elosulfase alfa was government funded. Thirteen patients (1-27 years) were enrolled. No new safety concerns were identified over 138 weeks. Most drug-related adverse events were mild or moderate in severity; none led to study discontinuation. After 49 weeks of treatment, median improvements from baseline were seen in the 6-minute walk test (+41.0 m), 3-minute stair climb test (+14.0 stairs/min), forced vital capacity (+16.4%), forced expiratory volume in 1 second (+14.1%), urine keratan sulfate (-7.1 µg/mg creatinine), and pain intensity. Growth, cardiac function, sleep, and quality of life results were mixed or stable. These results provide further evidence of the acceptable safety/tolerability profile of elosulfase alfa. The improvements in endurance, pulmonary function, and pain support findings from previous studies.

Introduction This study aims to clarify the role(s) of endogenous sex hormones to influence health outcomes in men, specifically to define the associations of plasma testosterone with incidence of cardiovascular events, cancer, dementia and mortality risk, and to identify factors predicting testosterone concentrations. Data will be accrued from at least three Australian, two European and four North American population-based cohorts involving approximately 20 000 men.Methods and analysis Eligible studies include prospective cohort studies with baseline testosterone concentrations measured using mass spectrometry and 5 years of follow-up data on incident cardiovascular events, mortality, cancer diagnoses or deaths, new-onset dementia or decline in cognitive function recorded. Data for men, who were not taking androgens or drugs suppressing testosterone production, metabolism or action; and had no prior orchidectomy, are eligible. Systematic literature searches were conducted from 14 June 2019 to 31 December 2019, with no date range set for searches. Aggregate level data will be sought where individual participant data (IPD) are not available. One-stage IPD random-effects meta-analyses will be performed, using linear mixed models, generalised linear mixed models and either stratified or frailty-augmented Cox regression models. Heterogeneity in estimates from different studies will be quantified and bias investigated using funnel plots. Effect size estimates will be presented in forest plots and non-negligible heterogeneity and bias investigated using subgroup or meta-regression analyses.Ethics and dissemination Ethics approvals obtained for each of the participating cohorts state that participants have consented to have their data collected and used for research purposes. The Androgens In Men Study has been assessed as exempt from ethics review by the Human Ethics office at the University of Western Australia (file reference number RA/4/20/5014). Each of the component studies had obtained ethics approvals; please refer to respective component studies for details. Research findings will be disseminated to the scientific and broader community via the publication of four research articles, with each involving a separate set of IPD meta-analyses (articles will investigate different, distinct outcomes), at scientific conferences and meetings of relevant professional societies. Collaborating cohort studies will disseminate findings to study participants and local communities.PROSPERO registration number CRD42019139668.

Abstract Background Women diagnosed with gynaecological cancer experience supportive care needs that require care provision to reduce the impact on their lives. International evidence suggests supportive care needs of women with gynaecological cancer are not being met and provision of holistic care is a priority area for action. Knowledge on gynaecological cancer supportive care needs is limited, specifically comparison of needs and cancer gynaecological subtype. Our aim was to identify supportive care needs of Western Australian women experiencing gynaecological cancer, their satisfaction with help and explore associations between participant’s demographic characteristics and identified needs. Methods A cross-sectional design incorporating a modified version of the Supportive Care Needs Survey – short form (SCNS-SF34) assessed 37 supportive care needs under five domains in conjunction with demographic data. Three hundred and forty three women with gynaecological cancer attending a tertiary public referral hospital completed the survey over 12 months. Statistical analysis was performed using the R environment for statistical computing. A linear regression model was fitted with factor scores for each domain and demographic characteristics as explanatory variables. Results Three hundred and three women (83%) identified at least one moderate or high level supportive care need. The five highest ranked needs were, ‘being informed about your test results as soon as feasible’ (54.8%), ‘fears about cancer spreading’ (53.7%), ‘being treated like a person not just another case’ (51.9%), ‘being informed about cancer which is under control or diminishing (that is, remission)’ (50.7%), and ‘being adequately informed about the benefits and side-effects of treatments before you choose to have them’ (49.9%). Eight of the top ten needs were from the ‘health system and information’ domain. Associations between supportive care items and demographic variables revealed ‘cancer type’, and ‘time since completion of treatment’ had no impact on level of perceived need for any domain. Conclusions Western Australian women with gynaecological cancer identified a high level of supportive care needs. The implementation of a supportive care screening tool is recommended to ensure needs are identified and care is patient-centred. Early identification and management of needs may help to reduce the burden on health system resources for managing ongoing needs.

Abstract Background The most appropriate treatment of pathological fractures from metastatic disease depends on several factors, one of the most important being predicted life expectancy. The aim of this study was to identify the variables that influence prognosis and utilise these to develop a novel scoring system to better predict life expectancy post-pathological fracture. Methods The records of all patients that presented with metastatic pathological fractures over a 10-year period from the only tertiary orthopaedic departments in Western Australia were retrospectively examined. Variables assessed were primary cancer type, fracture site, fixation method, cement augmentation, pre-morbid level of physical functioning, complication rate, treatment with chemotherapy or radiotherapy and appendicular, spinal and visceral metastatic load. Results A total of 233 patients were included. Median survival from fracture to death was 4.1 months. Median time from cancer diagnosis to pathological fracture was 14.2 months. There was a statistically significant association between patient survival and primary cancer type, physical functional score, spinal metastatic burden and use of chemotherapy or radiotherapy. Conclusion A novel scoring system has been developed that offers a survival probability based on patient’s individual circumstances. This can guide specialist management and offer patients a more accurate expectation of functional outcome and survival time.

Background Accurate disease mapping based on spatiotemporal data is an important aspect of public health surveillance, targeting interventions, and health service planning. This is achieved by public health surveillance organisations around the world through the construction of choropleth maps based on single spatiotemporal aggregations of finer resolution data. However, such maps are undermined by their dependence on the spatiotemporal units used. This dependence is described by the related modifiable areal and temporal unit problems (MAUP; MTUP), also known as change of support problems (COSPs). Aim To accurately map disease. Methods Using ischaemic stroke admissions and mental health-related ED presentations in metropolitan Perth between 2013 and 2016 as exemplars, we present a novel zonation overlay approach for disease mapping. This method involves aggregating fine resolution spatial data numerous times instead of just once, using the automated zonation construction software AZTool. Results Through implementing the zonation overlay method in combination with a rolling window of time, both the MAUP and the MTUP may be overcome in the context of disease mapping. Furthermore, the AZTool zonations act as a geographical encryption key, allowing fine resolution, precise maps to be constructed while protecting the privacy of individuals. Conclusion Health surveillance organisations continue to produce single aggregation choropleth maps of disease, without acknowledging their limitations except in rare cases. Producing such maps and suggesting they should guide policy makers, while being aware of but not acknowledging the impact of COSPs, could be described as scientific malfeasance. However, assuming that most researchers producing such maps are not intending to mislead, we must conclude that COSPs are poorly understood and their impact underestimated. The zonation overlay method we describe can help alleviate the consequences of this continued practice.

Summary: Background: Flavonoids, compounds found in plant-based foods and beverages, might ameliorate vascular damage and atherosclerosis. Therefore, our aim was to assess the association between flavonoid intake and hospital admissions due to atherosclerotic cardiovascular disease. Methods: In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study were cross-linked with Danish nationwide registries. Eligible participants were aged 50–65 years, had no previous history of atherosclerotic cardiovascular disease, and had completed a food-frequency questionnaire at baseline. We examined associations between flavonoid intake (calculated from food-frequency questionnaires with use of the Phenol-Explorer database) and hospital admissions for atherosclerotic cardiovascular disease, ischaemic heart disease, ischaemic stroke, or peripheral arterial disease. We obtained hazard ratios (HRs) using restricted cubic splines based on Cox proportional hazards models. Findings: Of the participants recruited to the Danish Diet, Cancer, and Health study between 1993 and 1997, our study population was comprised of 53 552 participants, with a median follow-up of 21 years (IQR 15–22). During follow-up, 8773 participants were admitted to hospital for atherosclerotic cardiovascular disease. We observed non-linear associations between flavonoid intake and hospital admissions, plateauing at total flavonoid intakes of approximately 1000 mg per day. Compared with an intake of 175 mg per day, an intake of 1000 mg per day was associated with a 14% lower risk of atherosclerotic cardiovascular disease (HR 0·86, 95% CI 0·81–0·91). For disease subtypes, we observed a 9% lower risk of ischaemic heart disease (0·91, 0·85–0·98), a non-significant 9% lower risk of ischaemic stroke (0·91, 0·82–1·01), and a 32% lower risk of peripheral artery disease (0·68, 0·60–0·78). The overall associations were stronger in smokers than in non-smokers, as well as stronger in consumers of high (>20 g per day) quantities of alcohol than in those consuming low-to-moderate (≤20 g per day) quantities. Interpretation: Our results suggest that ensuring an adequate consumption of flavonoid-rich foods, particularly in subpopulations at risk of atherosclerosis such as smokers and consumers of high quantities of alcohol might mitigate some of the risk of atherosclerotic cardiovascular disease. More studies are needed to support and validate these data. Funding: Danish Cancer Society.

The fatty acids (FAs) of human milk (HM) are the building blocks of the HM lipidome, contributing to infant health and development; however, this has not been comprehensively characterised with respect to infant intake. Eighteen Western Australian mother–infant dyads provided monthly longitudinal HM samples during six months of exclusive breastfeeding. Monthly anthropometric measurements, health data and basic maternal food frequency data were also collected. At three months, infant 24 h milk intake and total lipid intake were measured. The FA profile was analysed using gas chromatography–mass spectrometry. Linear regression and Pearson’s correlation were used to identify associations between HM FA composition, HM FA intake, maternal characteristics and infant growth and developmental outcomes. Mean infant intake of total lipids was 29.7 ± 9.4 g/day. HM FA composition exhibited wide variation between dyads and throughout lactation. Infant intake of a number of FAs, including C15:0, C18:1, C18:2 and C20:3, was positively related to infant growth (all p < 0.001). There were no relationships detected between C22:5 and C20:5 and infant head circumference. Infant total lipid intake and the infant intake of many FAs play essential roles in infant growth and development. This study highlights the important relationships of many HM FAs not previously described, including C15:0 and C18:2 species. Infant outcomes should be considered in the context of intake in future HM studies.

Human milk (HM) components may influence infant growth and development. This study aimed to investigate relationships between infant body composition (BC) and HM lactose, insulin, and glucose (concentrations and calculated daily intakes (CDI)) as well as 24-h milk intake and maternal BC at 3 months postpartum. HM samples were collected at 2 months postpartum. Infant and maternal BC was assessed with bioimpedance spectroscopy. Statistical analysis used linear regression accounting for infant birth weight. 24-h milk intake and CDI of lactose were positively associated with infant anthropometry, lean body mass and adiposity. Higher maternal BC measures were associated with lower infant anthropometry, z-scores, lean body mass, and adiposity. Maternal characteristics including BC and age were associated with concentrations and CDI of HM components, and 24-h milk intake. In conclusion, 24-h intake of HM and lactose as well as maternal adiposity are related to development of infant BC.

This study aimed to investigate relationships between infant abdominal visceral and subcutaneous adiposity and human milk (HM) components and maternal body composition (BC) during first year of lactation. Subcutaneous-abdominal depth (SAD), subcutaneous-abdominal fat area (SFA), visceral depth (VD) and preperitoneal fat area of 20 breastfed infants were assessed at 2, 5, 9 and 12 months using ultrasound. Maternal BC was determined with bioimpedance spectroscopy. HM macronutrients and bioactive components concentrations and infant 24-h milk intake were measured and calculated daily intakes (CDI) determined. Maternal adiposity associated with infant SFA (negatively at 2, 5, 12, positively at 9 months, all overall p < 0.05). 24-h milk intake positively associated with infant SAD (p = 0.007) and VD (p = 0.013). CDI of total protein (p = 0.013), total carbohydrates (p = 0.004) and lactose (p = 0.013) positively associated with SFA. Lactoferrin concentration associated with infant VD (negatively at 2, 12, positively at 5, 9 months, overall p = 0.003). CDI of HM components and maternal adiposity have differential effects on development of infant visceral and subcutaneous abdominal adiposity. Maintaining healthy maternal BC and continuing breastfeeding to 12 months and beyond may facilitate favourable BC development reducing risk of obesity.