Protocol for economic evaluation alongside the SHINE (Supporting Healthy Image, Nutrition and Exercise) cluster randomised controlled trial

INTRODUCTION: Limited evidence exists on the cost-effectiveness of interventions to prevent obesity and promote healthy body image in adolescents. The SHINE (Supporting Healthy Image, Nutrition and Exercise) study is a cluster randomised control trial (cRCT) aiming to deliver universal education about healthy nutrition and physical activity to adolescents, as well as targeted advice to young people with body image concerns who are at risk of developing disordered eating behaviours. This paper describes the methods for the economic evaluation of the SHINE cRCT, to determine whether the intervention is cost-effective as an obesity prevention measure. METHODS AND ANALYSIS: A public payer perspective will be adopted, with intervention costs collected prospectively. Within-trial cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) will quantify the incremental costs and health gains of the intervention as compared with usual practice (ie, teacher-delivered curriculum). CEA will present results as cost per body mass index unit saved. CUA will present results as cost per quality-adjusted life year gained. A modelled CUA will extend the target population, time horizon and decision context to provide valuable information to policymakers on the potential for incremental cost offsets attributable to disease prevention arising from intervention. Intervention costs and effects will be extrapolated to the population of Australian adolescents in Grade 7 of secondary school (approximate age 13 years) and modelled over the cohort\u27s lifetime. Modelled CUA results will be presented as health-adjusted life years saved and healthcare cost-savings of diseases averted. Incremental cost-effectiveness ratios will be calculated as the difference in costs between the intervention and comparator divided by the difference in benefit. Semi-structured interviews with key intervention stakeholders will explore the potential impact of scalability on cost-effectiveness. These data will be thematically analysed to inform sensitivity analysis of the base case economic evaluation, such that cost-effectiveness evidence is reflective of the potential for scalability. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Deakin University Human Research Ethics Committee (#2017-269) and the Victorian Department of Education and Training (#2018_003630). Study findings will be disseminated through peer-reviewed academic papers and participating schools will receive annual reports over the 3 years of data collection. TRIAL REGISTRATION NUMBER: ACTRN 12618000330246; Pre-results

Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited

The chemotherapeutic agent doxorubicin (DOX) has significantly increased survival rates of pediatric and adult cancer patients. However, 10% of pediatric cancer survivors will 10–20 years later develop severe dilated cardiomyopathy (DCM), whereby the exact molecular mechanisms of disease progression after this long latency time remain puzzling. We here revisit the hypothesis that elevated apoptosis signaling or its increased likelihood after DOX exposure can lead to an impairment of cardiac function and cause a cardiac dilation. Based on recent literature evidence, we first argue why a dilated phenotype can occur when little apoptosis is detected. We then review findings suggesting that mature cardiomyocytes are protected against DOX-induced apoptosis downstream, but not upstream of mitochondrial outer membrane permeabilisation (MOMP). This lack of MOMP induction is proposed to alter the metabolic phenotype, induce hypertrophic remodeling, and lead to functional cardiac impairment even in the absence of cardiomyocyte apoptosis. We discuss findings that DOX exposure can lead to increased sensitivity to further cardiomyocyte apoptosis, which may cause a gradual loss in cardiomyocytes over time and a compensatory hypertrophic remodeling after treatment, potentially explaining the long lag time in disease onset. We finally note similarities between DOX-exposed cardiomyocytes and apoptosis-primed cancer cells and propose computational system biology as a tool to predict patient individual DOX doses. In conclusion, combining recent findings in rodent hearts and cardiomyocytes exposed to DOX with insights from apoptosis signal transduction allowed us to obtain a molecularly deeper insight in this delayed and still enigmatic pathology of DC

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Systematic review of incidence, prevalence, and trends in health outcomes for Australian and New Zealand paramedics

Introduction The paramedic role carries inherent risk to practitioner health, due to a combination of work characteristics and the employment practices of different organizations. Emerging evidence suggests that paramedics worldwide may face a range of negative health outcomes. The purpose of this article was to systematically review the literature of paramedic health outcomes in the Australian and New Zealand context. Methods A systematic search of key databases and gray literature was conducted to identify all available studies reporting on quantitative health outcomes for paramedics working in Australia or New Zealand. The review was conducted using the JBI methodology for prevalence studies and uses a narrative synthesis approach to reporting. Results There were k = 20 studies that met inclusion criteria, and most used Australian samples. Results indicated between 57.3–66.5% of paramedics studied were classified as overweight or obese, while up to 80% reported poor sleep, and 55.6% reported fatigue. Incidence rates per 100,000 full-time equivalent (FTE) included 26.62 for completed suicide, 5.46 for drug-caused death, and 9.3 for workplace fatalities. The most recent incidence per 1,000 FTE for injury compensation claims was 141.4. Conclusions Australian and New Zealand paramedics demonstrate poor health according to several metrics. Our sample demonstrated considerably worse health than the general population or similar occupations. There is a minimal amount of trend data available; therefore, it was difficult to ascertain if rates are changing. The range of health outcomes studied was limited, and correlations between different health outcomes were rarely considered by authors. Data relating to specific rates for gender and sexuality, location of work, and First Nations status or ethnicity was often not available

Healthy food and beverages in senior community football club canteens in New South Wales, Australia

Issue addressed: Little is known of the extent to which senior sports clubs support the consumption of healthy food and beverages. This study of senior community football clubs aimed to describe: i) the food and beverages available in club canteens; ii) the perceived acceptability of club representatives (e.g. club president or secretary) to selling healthy food and beverages in club canteens; iii) the perceived barriers of club representatives to providing healthy food and beverage options in their club canteen; iv) the associations between the availability of healthy options in canteens, perceived barriers to healthy food and drink availability, and club characteristics; and (v) the food and beverages usually purchased from canteens by club members. Methods: The study involved 70 senior community football clubs (Australian Rules Football, Soccer, Rugby League and Rugby Union) across New South Wales, Australia. Club representatives and club members took part in cross-sectional telephone surveys. Results: The most frequently available items at club canteens were regular soft drinks and potato chips or other salty snacks (available at 99% of clubs). Approximately two-thirds (66%) of club representatives agreed or strongly agreed that clubs should provide a greater variety of healthy food options. Perishability and lack of demand were the most frequently cited barriers to healthy food provision. Healthy food options were more available at AFL clubs compared with other football codes. Overall, 6% of club members reported purchasing a healthy food option. Conclusions: Senior community football clubs primarily stock and sell unhealthy food and beverage items. There is support within clubs for providing more healthy options; however, clubs face a number of barriers to the inclusion of healthy foods in club canteens

High-intensity interval training is effective at increasing exercise endurance capacity and is well tolerated by adults with cystic fibrosis

Background: To optimize outcomes in people with cystic fibrosis (CF), guidelines recommend 30 to 60 min of moderate-intensity aerobic exercise on most days. Accumulating this volume of exercise contributes importantly to the substantial treatment burden associated with CF. Therefore, the main aim of this study was to investigate the effects of low-volume high-intensity interval training (HIIT) on exercise capacity in people with CF. Methods: This randomized controlled trial included people with CF aged ≥15 years, who were allocated to either eight weeks of thrice-weekly 10-min sessions of HIIT (experimental group) or eight weeks of weekly contact (control group). Before and after the intervention period, participants completed measurements of time to symptom limitation (Tlim) during a constant work rate cycle ergometry test (primary outcome), and maximal work rate (Wmax) during a ramp-based cycle ergometry test and health-related quality of life (HRQoL). Results: Fourteen participants (median (IQR) age 31 (28, 35) years, forced expiratory volume in 1 second (FEV1) 61 (45, 80) % predicted) were included (seven in each group). Compared to the control group, participants in the experimental group demonstrated a greater magnitude of change in Tlim, Wmax (p = 0.017 for both) and in the physical function domain of HRQoL (p = 0.03). No other between-group differences were demonstrated. Mild post-exercise muscle soreness was reported on a single occasion by four participants. Overall, participants attended 93% of all HIIT sessions. Discussion: Eight weeks of low-volume (i.e., 30-min/week) HIIT produced gains in exercise capacity and self-reported physical function and was well tolerated by people with C

Alcohol sponsorship of community football clubs : the current situation

Issue addressed: There is accumulating evidence supporting a link between alcohol industry sponsorship and alcohol-related problems in both community and elite-level sports. Little is known, however, about the current status of such sponsorship, particularly of community sport. This study aimed to assess associations between alcohol industry sponsorship and different community football clubs in Australia. Methods: The study involved 101 community football clubs across New South Wales, Australia. One representative from each club took part in a cross-sectional telephone survey designed to assess club (football code, number of players, socioeconomic and geographic descriptors) and alcohol industry sponsorship (money, equipment, free alcohol or discounted alcohol) characteristics. Chi-square analysis was used to test associations between club characteristics, and: i) any alcohol industry sponsorship; and ii) type of sponsorship. Results: Eighty-eight per cent of clubs reported receiving sponsorship from the alcohol industry, and most clubs (82%) were sponsored by a licensed premises. There were no significant associations between club characteristics and source of alcohol industry sponsorship. However, small clubs were found to be significantly more likely to receive free or discounted alcohol sponsorship than larger clubs (p=0.05). Conclusions: This exploratory study suggests a significant presence of alcohol industry sponsorship among community football clubs in Australia.<br /

IL-2/IL-2Ab Complexes Induce Regulatory T Cell Expansion and Protect against Proteinuric CKD

Regulatory T cells (Tregs) help protect against autoimmune renal injury. The use of agonist antibodies and antibody/cytokine combinations to expand Tregs in vivo may have therapeutic potential for renal disease. Here, we investigated the effects of administering IL-2/IL-2Ab complexes in mice with adriamycin nephropathy, a model of proteinuric kidney disease that resembles human focal segmental glomerulosclerosis. Injecting IL-2/IL-2Ab complexes before or, to a lesser extent, after induction of disease promoted expansion of Tregs. Furthermore, administration of this complex was renoprotective, evidenced by improved renal function, maintenance of body weight, less histologic injury, and reduced inflammation. IL-2/IL-2Ab reduced serum IL-6 and renal expression of IL-6 and IL-17 but enhanced expression of IL-10 and Foxp3 in the spleen. In vitro, the addition of IL-2/IL-2Ab complexes induced rapid STAT-5 phosphorylation in CD4 T cells. In summary, these data suggest that inducing the expansion of Tregs by administering IL-2/IL-2Ab complexes is a possible strategy to treat renal disease