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Background Poor social health is associated with increased risk of cardiovascular disease (CVD). Recent research suggests that different social health domains should be considered separately as the implications for health and possible interventions may differ. Aim To assess social isolation, low social support and loneliness as predictors of CVD. Methods Secondary analysis of 11,486 community-dwelling, Australians, aged 70 years and over, free of CVD, dementia, or significant physical disability, from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Social isolation, social support (Revised Lubben Social Network Scale), and loneliness were assessed as predictors of CVD using Cox proportional-hazard regression. CVD events included fatal CVD, heart failure hospitalization, myocardial infarction and stroke. Analyses were adjusted for established CVD risk factors. Results Individuals with poor social health were 42 % more likely to develop CVD (p = 0.01) and twice as likely to die from CVD (p = 0.02) over a median 4.5 years follow-up. Interaction effects indicated that poorer social health more strongly predicted CVD in smokers (HR 4.83, p = 0.001, p-interaction = 0.01), major city dwellers (HR 1.94, p < 0.001, p-interaction=0.03), and younger older adults (70-75 years; HR 2.12, p < 0.001, p-interaction = 0.01). Social isolation (HR 1.66, p = 0.04) and low social support (HR 2.05, p = 0.002), but not loneliness (HR 1.4, p = 0.1), predicted incident CVD. All measures of poor social health predicted ischemic stroke (HR 1.73 to 3.16). Conclusions Among healthy older adults, social isolation and low social support may be more important than loneliness as cardiovascular risk factors. Social health domains should be considered in future CVD risk prediction models.

ObjectiveThis study aims to determine the relationship between door-to-balloon delay in primary percutaneous coronary intervention and ST-elevation myocardial infarction (MI) outcomes and examine for potential effect modifiers.MethodsWe conducted a systematic review and meta-analysis of prospective observational studies that have investigated the relationship of door-to-balloon delay and clinical outcomes. The main outcomes include mortality and heart failure.Results32 studies involving 299 320 patients contained adequate data for quantitative reporting. Patients with ST-elevation MI who experienced longer (>90 min) door-to-balloon delay had a higher risk of short-term mortality (pooled OR 1.52, 95% CI 1.40 to 1.65) and medium-term to long-term mortality (pooled OR 1.53, 95% CI 1.13 to 2.06). A non-linear time–risk relation was observed (P=0.004 for non-linearity). The association between longer door-to-balloon delay and short-term mortality differed between those presented early and late after symptom onset (Cochran’s Q 3.88, P value 0.049) with a stronger relationship among those with shorter prehospital delays.ConclusionLonger door-to-balloon delay in primary percutaneous coronary intervention for ST-elevation MI is related to higher risk of adverse outcomes. Prehospital delays modified this effect. The non-linearity of the time–risk relation might explain the lack of population effect despite an improved door-to-balloon time in the USA.Clinical trial registrationPROSPERO (CRD42015026069).

ASPirin in Reducing Events in the Elderly (ASPREE), a placebo-controlled prevention trial of low dose aspirin, provided the opportunity to establish a biospecimen biobank from initially healthy persons aged 70+ years for future research. The ASPREE Healthy Ageing Biobank (ASPREE Biobank) collected, processed and stored blood and urine samples at -80degC or under nitrogen vapour at two timepoints, three years apart, from a willing subset of Australian ASPREE participants. Written informed consent included separate opt-in questions for biomarker and genetic testing. Fractionated blood and urine were aliquoted into multiple low-volume, barcoded cryotubes for frozen storage within 4 hours of collection. Specially designed and outfitted mobile laboratories provided opportunities for participation by people in regional and rural areas. Detailed, high quality demographic, physiological and clinical data were collected annually through the ASPREE trial. 12,219 participants contributed blood/urine at the first timepoint, 10,617 of these older adults provided 3-year follow-up samples, and an additional 1,712 provided saliva for DNA. The mean participant age was 74 years, 54% were female and 46% lived outside major cities. Despite geographical and logistical challenges, nearly 100% of blood/urine specimens were processed and frozen within 4 hours of collection into >1.4 million aliquots. After a median of 4.7 years, major clinical events among ASPREE Biobank participants included 332 with dementia, 613 with cardiovascular disease events, 1259 with cancer, 357 with major bleeds and 615 had died. The ASPREE Biobank houses and curates a large number of biospecimens collected prior to the clinical manifestations of major disease, and 3-year follow-up samples, all linked to high quality, extensive phenotypic information. This provides the opportunity to identify or validate diagnostic, prognostic and predictive biomarkers, and potentially study biological effectors, of ageing-related diseases or maintenance of older-age good health.

Clinical trials have shown that radial access percutaneous coronary intervention (PCI) is associated with improved patient outcomes compared to femoral artery access. However, few studies have evaluated the cost-effectiveness of radial access PCI. This analysis sought to evaluate the cost-effectiveness of transradial versus transfemoral access PCI for patients with acute coronary syndrome (ACS) using data from the Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) trial. A decision analytic Markov model was constructed from an Australian health care perspective with a 2 year time horizon. The model simulated recurrent cardiovascular disease and death post PCI among a hypothetical cohort of 1000 individuals with ACS. Population and efficacy data were based on the MATRIX trial. Cost and utility data were drawn from published sources. Over a 2-year time horizon, radial access was predicted to save 12 (discounted) quality adjusted life years (QALYs) compared with femoral access PCI. Cost savings (discounted) amounted to AUD $51,305. Hence from a health economic point of view, radial access PCI was dominant over femoral access PCI. Sensitivity analyses supported the robustness of these findings. Radial access PCI is likely to be associated with both better outcomes and lower costs compared to femoral access PCI over 2 years post procedure. In conclusion, these findings support radial access being the preferred approach in PCI for ACS.

Cardiovascular disease contributes substantially to global mortality and morbidity. Respiratory tract infections, particularly influenza, may trigger an increase in the short-term risk of acute myocardial infarction (AMI) and stroke. Recent studies have also linked this risk to other respiratory viruses, including respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pathogen-specific relative contributions, the strength of their associations, and overall public health significance are poorly understood. Assuming causal links, understanding, quantifying, and comparing the effects of different pathogens as triggering factors for acute cardiovascular events is critical to guide future research and prevention. Our aim is to conduct a systematic review to examine the relative effects of laboratory-confirmed respiratory virus infections as triggers for acute myocardial infarction and stroke. We will conduct a comprehensive search of Ovid MEDLINE, PubMed, Ovid Embase, Cochrane Library Central Register of Controlled Trials, and Web of Science, from inception to the end of March 2024. Studies capturing respiratory viral infection(s) using laboratory-confirmatory methods, incidence of AMI or stroke (ischaemic or haemorrhagic), and those involving human participants in any country, will be assessed for eligibility. We will include the following analytical epidemiological study types: randomised controlled trials, cohort and case-control studies, self-controlled case series, and case-crossover designs. We will not impose restrictions on the date, language, study population, geographical region, or sample size, to minimise the risk of introducing biases. Search results will be screened for eligibility by two independent reviewers, and discrepancies resolved by consensus and/or arbitration by a third reviewer. We will assess the risk of bias among the included studies by adopting the Cochrane Collaboration tools for randomised and non-randomised studies. The overall quality of studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We will examine sources of heterogeneity, and if studies are sufficiently homogeneous, a meta-analysis will be conducted to calculate the pooled effect sizes. Reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42024494997.

IntroductionThe world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD). This paper presents the protocol for the STAtins in Reducing Events in the Elderly (STAREE) trial, a randomised double-blind placebo-controlled trial examining the effects of statins in community dwelling older people without CVD, diabetes or dementia.Methods and analysisWe will conduct a double-blind, randomised placebo-controlled trial among people aged 70 years and over, recruited through Australian general practice and with no history of clinical CVD, diabetes or dementia. Participants will be randomly assigned to oral atorvastatin (40 mg daily) or matching placebo (1:1 ratio). The co-primary endpoints are disability-free survival defined as survival-free of dementia and persistent physical disability, and major cardiovascular events (cardiovascular death or non-fatal myocardial infarction or stroke). Secondary endpoints are all-cause death, dementia and other cognitive decline, persistent physical disability, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, heart failure, atrial fibrillation, fatal and non-fatal cancer, all-cause hospitalisation, need for permanent residential care and quality of life. Comparisons between assigned treatment arms will be on an intention-to-treat basis with each of the co-primary endpoints analysed separately in time-to-first-event analyses using Cox proportional hazards regression models.Ethics and disseminationSTAREE will address uncertainties about the preventive effects of statins on a range of clinical outcomes important to older people. Institutional ethics approval has been obtained. All research outputs will be disseminated to general practitioner co-investigators and participants, published in peer-reviewed journals and presented at national and international conferences.Trial registration numberNCT02099123.

Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill—a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14–23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen. The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability. National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.

Machine learning (ML) is increasingly applied to predict adverse postoperative outcomes in cardiac surgery. Commonly used ML models fail to translate to clinical practice due to absent model explainability, limited uncertainty quantification, and no flexibility to missing data. We aimed to develop and benchmark a novel ML approach, the uncertainty-aware attention network (UAN), to overcome these common limitations. Two Bayesian uncertainty quantification methods were tested, generalized variational inference (GVI) or a posterior network (PN). The UAN models were compared with an ensemble of XGBoost models and a Bayesian logistic regression model (LR) with imputation. The derivation datasets consisted of 153,932 surgery events from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Cardiac Surgery Database. An external validation consisted of 7343 surgery events which were extracted from the Medical Information Mart for Intensive Care (MIMIC) III critical care dataset. The highest performing model on the external validation dataset was a UAN-GVI with an area under the receiver operating characteristic curve (AUC) of 0.78 (0.01). Model performance improved on high confidence samples with an AUC of 0.81 (0.01). Confidence calibration for aleatoric uncertainty was excellent for all models. Calibration for epistemic uncertainty was more variable, with an ensemble of XGBoost models performing the best with an AUC of 0.84 (0.08). Epistemic uncertainty was improved using the PN approach, compared to GVI. UAN is able to use an interpretable and flexible deep learning approach to provide estimates of model uncertainty alongside state-of-the-art predictions. The model has been made freely available as an easy-to-use web application demonstrating that by designing uncertainty-aware models with innately explainable predictions deep learning may become more suitable for routine clinical use.

Fly-In-Fly-Out (FIFO) workers travel to work at isolated locations, and rotate continuous workdays with leave periods at home, and such work practice is common in the offshore oil and gas and onshore mining industry worldwide. The COVID-19 pandemic and accompanying public health actions appear to have had a negative impact on several health-related behaviours among the general population. However, little is known about the impact of the COVID-19 pandemic on the health behaviours of FIFO workers, who have shown higher pre-pandemic rates of risky behaviours than the general population in Australia. This study examined the health-related behaviours of FIFO workers in the mining industry during the COVID-19 pandemic. A descriptive cross-sectional study was conducted. FIFO workers from an Australian mining company who underwent COVID-19 screening between May and November 2020 completed an online survey about their regular health-related behaviours. The independent sample t-test and Pearson's chi-square test where appropriate were conducted to examine the differences between males and females for the behavioural outcomes. A total of 768 FIFO workers (633 males and 135 females) participated in the study. Prevalence of smoking was high (32%). Males smoked more cigarettes per day than females (15.2±7.0 vs 13.1±7.1, p = .174). Most participants (74.7%) drank alcohol on more than two days per week. Compared to females, more males (20.2% vs 8.0%) consumed alcohol at short-term harmful levels (p = .010). About a third (34.4%) of the workers (33.5% of males and 38.5% of females, p = .264) engaged in inadequate moderate-vigorous exercises/physical activity. About a third (33.1%) of workers (33.7% of males and 30.4% of females; p = .699) had multiple risk behaviours. Prevalence of multiple risk behaviours was high. Interventions aimed at the prevention of risky health-related behaviours should target the different behavioural patterns and may require emphasis on gender-informed techniques particularly when addressing alcohol consumption.

Late-life depression is common and often inadequately managed using existing therapies. Depression is also associated with increased markers of inflammation, suggesting a potential role for anti-inflammatory agents. ASPREE-D is a sub-study of ASPREE, a large multi-centre, population-based, double-blind, placebo-controlled trial of aspirin vs placebo in older Australian and American adults (median follow-up: 4.7 years) of whom 1879 were depressed at baseline. Participants were given 100 mg daily dose of aspirin or placebo. Depressive symptoms were assessed annually using the validated, self-rated short version of the Center for Epidemiological Studies Depression scale. There was a significant increase in depressive scores (0.6; 95% CI 0.2 to 0.9; χ2 (1) = 10.37; p = 0.001) and a decreased score in the mental health component of a quality of life scale (–0.7; 95% CI –1.4 to –0.1; χ2 (1) = 4.74; p = 0.029) in the aspirin group compared to the placebo group. These effects were greater in the first year of follow-up and persisted throughout the study, albeit with small to very small effect sizes. This study failed to demonstrate any benefit of aspirin in the long-term course of depression in this community-dwelling sample of older adults over a 5-year period, and identified an adverse effect of aspirin in the course of depression in those with pre-existing depressive symptoms.