The impact of extreme heat on mass-gathering sporting events: Implications for Australia and other countries.

OBJECTIVES: As temperatures increase across the globe due to climate change, human exposure to extreme heat is a public health challenge. During sporting events, athletes, officials, spectators, and staff are at risk of heat stress and resulting illness. The objective of this review was to explore the impact of heat on the health outcomes of these groups and the wider health system and discuss implications for outdoor mass-gathering sporting events in Australia. DESIGN: A systematic review was undertaken to identify literature published from 2010 to 2023. METHODS: Seven databases were searched: Web of Science, SportDiscus, Scopus, Medline, CINAHL, Emcare, and PsychInfo, for relevant key search terms such as heatwave, heat stress, extreme heat, stadium, arena, sports facilit*, sport, athletic, and Olympic. An inductive thematic analysis was undertaken. Articles were quality checked using Joanna Briggs Institute critical appraisal tools and data were extracted, tabulated, and synthesized. RESULTS: Forty papers were included in the final analysis: 17 quantitative, and 23 descriptive and qualitative (including reviews). Health outcomes explored across the literature included exertional heat illness, exertional heat stroke, hyperthermia, and general heat related illness. Six recommendation themes emerged: planning, mitigation strategies, medical, policy, research, and education. CONCLUSIONS: The impact of heat on health outcomes during sporting events is significant, and should be considered by individuals, coaches, officials, and organizers before, during, and after mass-gathering sporting events. These findings can inform evidence-based preparedness strategies to protect the health of those attending and competing in mass-gathering sporting events now and into the future.

Examining the relationship between heatwaves and fatal drowning: a case study from Queensland, Australia.

BACKGROUND: Globally, drowning is a leading cause of injury-related harm, which is heavily impacted by environmental conditions. In Australia, fatal unintentional drowning peaks in summer, yet the impact of prolonged periods of hot weather (heatwave) on fatal drowning has not previously been explored. METHODS: Using a case-crossover approach, we examined the difference in drowning risk between heatwave and non-heatwave days for the Australian state of Queensland from 2010 to 2019. Heatwave data, measured by the excess heat factor, were acquired from the Bureau of Meteorology. Incidence rate ratios (IRRs) were calculated by sex, age of drowning decedent, category of drowning incident (International Classification of Diseases-10 codes) and heatwave severity. Excess drowning mortality during heatwaves was also calculated. RESULTS: Analyses reveal increased fatal drowning risk during heatwave for males (IRR 1.22, 95% CI 0.92 to 1.61), people aged 65+ years (IRR 1.36, 95% CI 0.83 to 2.24), unintentional drowning (IRR 1.28, 95% CI 0.98 to 1.69) and during severe heatwaves (IRR 1.26, 95% CI0.88 to 1.82). There were 13 excess drowning deaths due to heatwave over the study period. DISCUSSION: The findings confirm an increased risk of fatal drowning during heatwaves. With increased likelihood and severity of heatwaves, this information should be used to inform drowning prevention, in particular the timing of public awareness campaigns and patrolling of supervised aquatic locations. CONCLUSIONS: Water safety and patrolling organisations, as well as first responders, need to prepare for more drowning deaths during heatwave conditions. In addition, drowning prevention education ahead of heatwaves is needed for recreational swimmers, and older people, particularly those with comorbidities which may be further exacerbated by a heatwave.

Endoscope-Assisted Visualization of the Internal Auditory Canal Using the Middle Fossa Approach.

HYPOTHESIS: Angled endoscopes have been postulated to increase visualization of the internal auditory canal (IAC); however, few studies have quantified the extent of IAC visualization using endoscopes of varying angles. BACKGROUND: Preservation of the bony labyrinth in middle fossa (MF) vestibular schwannoma surgery may limit visualization of the lateral IAC. We sought to determine the extent to which IAC visualization is increased with endoscopes in these situations. METHODS: Computed tomography (CT) scans were acquired before and after two cadaveric MF bony drill-outs. An atlas-based method was used to localize the IAC in the preprocedure CT and then registered with the postprocedure CT using standard image registration methods. Virtual microscope and endoscope positions and angles of approach were determined in a 3D rendering environment. Using ray casting techniques, the percentage of IAC surface area visible (unobscured by bony structures) with the microscope and 0°, 30°, and 45° endoscopes was calculated. RESULTS: For cadaver 1, the microscope led to visible IAC surface areas of 72%, whereas 0°, 30°, and 45° endoscopes visualized 58%, 79%, and 84%, respectively. For cadaver 2, the microscope led to visible surface areas of 67%, whereas the same endoscopes visualized 66%, 84%, and 84%, respectively. CONCLUSIONS: Using a microscope yields similar proportions of visible IAC surface area to a 0° endoscope in MF bony drill-outs. Increased visualization of the IAC is possible with more angled endoscopes. Using angled endoscopes may facilitate improved tumor dissection in the lateral IAC with neural and vascular preservation in vestibular schwannoma surgery aimed at hearing preservation.

Determining the Impact of Heatwaves on Emergency Ambulance Calls in Queensland: A Retrospective Population-Based Study.

Heatwaves are a significant and growing threat to the health and well-being of the residents of Queensland, Australia. This threat is increasing due to climate change. Excess heat increases the demand for health services, including ambulance calls, and the purpose of this study was to explore this impact across Queensland. A state-wide retrospective analysis of heatwaves and emergency 'Triple Zero' (000) calls to Queensland Ambulance (QAS) from 2010-2019 was undertaken. Call data from the QAS and heatwave data from the Bureau of Meteorology were analysed using a case-crossover approach at the postcode level. Ambulance calls increased by 12.68% during heatwaves. The effect was greatest during low-severity heatwaves (22.16%), followed by severe (14.32%) and extreme heatwaves (1.16%). The impact varied by rurality, with those living in very remote areas and major cities most impacted, along with those of low and middle socioeconomic status during low and severe intensity heat events. Lag effects post-heatwave continued for at least 10 days. Heatwaves significantly increase ambulance call centre workload, so ambulance services must actively prepare resources and personnel to address increases in heatwave frequency, duration, and severity. Communities must be informed of the risks of heatwaves at all severities, particularly low severity, and the sustained risks in the days following a heat event.

Heatwaves and mortality in Queensland 2010-2019: implications for a homogenous state-wide approach.

Heatwaves are a significant cause of adverse health outcomes and mortality in Australia, worsening with climate change. In Queensland, the northeastern-most state, little is known about the impact of heatwaves outside of the capital city of Brisbane. This study aims to explore the impact of heatwaves on mortality across various demographic and environmental conditions within Queensland from 2010 to 2019. The Excess Heat Factor was used to indicate heatwave periods at the Statistical Area 2 (SA2) level. Registered deaths data from the Australian Bureau of Statistics and heatwave data from the Bureau of Meteorology were matched using a case-crossover approach. Relative risk and 95% confidence intervals were calculated across years, regions, age, sex, rurality, socioeconomic status, and cause of death. Heatwaves were associated with a 5% increase in all-cause mortality compared to deaths on non-heatwave days, with variability across the state. The risk of death on a heatwave day versus a non-heatwave day varied by heatwave severity. Individuals living in urban centers, the elderly, and those living in regions of lower socioeconomic status were most impacted by heatwave mortality. The relative risk of dying from neoplasms, nervous system conditions, respiratory conditions, and mental and behavioral conditions increased during heatwaves. As heatwaves increase in Queensland due to climate change, understanding the impact of heatwaves on mortality across Queensland is important to tailor public health messages. There is considerable variability across communities, demographic groups, and medical conditions, and as such messages need to be tailored to risk.

Development of an improved and specific inhibitor of NADPH oxidase 2 to treat traumatic brain injury.

NADPH oxidases (NOX's), and the reactive oxygen species (ROS) they produce, play an important role in host defense, thyroid hormone synthesis, apoptosis, gene regulation, angiogenesis and other processes. However, overproduction of ROS by these enzymes is associated with cardiovascular disease, fibrosis, traumatic brain injury (TBI) and other diseases. Structural similarities between NOX's have complicated development of specific inhibitors. Here, we report development of NCATS-SM7270, a small molecule optimized from GSK2795039, that inhibited NOX2 in primary human and mouse granulocytes. NCATS-SM7270 specifically inhibited NOX2 and had reduced inhibitory activity against xanthine oxidase in vitro. We also studied the role of several NOX isoforms during mild TBI (mTBI) and demonstrated that NOX2 and, to a lesser extent, NOX1 deficient mice are protected from mTBI pathology, whereas injury is exacerbated in NOX4 knockouts. Given the pathogenic role played by NOX2 in mTBI, we treated mice transcranially with NCATS-SM7270 after injury and revealed a dose-dependent reduction in mTBI induced cortical cell death. This inhibitor also partially reversed cortical damage observed in NOX4 deficient mice following mTBI. These data demonstrate that NCATS-SM7270 is an improved and specific inhibitor of NOX2 capable of protecting mice from NOX2-dependent cell death associated with mTBI.

An orally available cancer drug AZD6738 prevents type 1 diabetes.

Type 1 diabetes (T1D) affects three million Americans, with 80 new people diagnosed each day. T1D is currently uncurable and there is an urgent need to develop additional drug candidates to achieve the prevention of T1D. We propose AZD6738 (ATRi), an orally available drug currently in phases I and II of clinical trials for various cancers, as a novel candidate to prevent T1D. Based on previously reported findings of ATRi inducing cell death in rapidly proliferating T cells, we hypothesized that this drug would specifically affect self-antigen activated diabetogenic T cells. These cells, if left unchecked, could otherwise lead to the destruction of pancreatic ß cells, contributing to the development of T1D. This work demonstrates that increasing the duration of ATRi treatment provides extended protection against T1D onset. Remarkably, 5-week ATRi treatment prevented T1D in a robust adoptive transfer mouse model. Furthermore, the splenocytes of animals that received 5-week ATRi treatment did not transfer immune-mediated diabetes, while the splenocytes from control animal transferred the disease in 10 days. This work shows that ATRi prevents T1D by specifically inducing cell death in self-antigen activated, highly proliferative diabetogenic T cells through the induction of DNA damage, resulting in the inhibition of IFNγ production and proliferation. These findings support the consideration of repurposing ATRi for T1D prevention.

Comparing rural traffic safety in Canada and Australia: a scoping review of the literature.

INTRODUCTION: The reduction of road fatalities is a priority established by the WHO and ratified by the UN. Rates of road fatalities are disproportionately high in rural areas in both Australia and Canada, two Commonwealth countries with comparable healthcare systems and rural health challenges. The purpose of this review was to compare and contrast the epidemiology, risk factors and prevention strategies of rural road fatalities in both countries to inform the next steps for prevention. METHODS: A scoping literature review was undertaken systematically to search for peer-reviewed literature published from January 2000 to June 2021. Articles were reviewed from five databases (EMCARE, Medline, CINAHL, Scopus and Informit). Search terms were adapted to suit each database and included combinations of keywords such as 'traffic accident', 'fatality', 'rural/remote', 'Australia' and 'Canada'. Themes and data associated with the research outcomes were extracted and tabulated. RESULTS: Forty-three papers were identified as relevant: 14 exploring epidemiology, 25 investigating risk factors and 37 proposing prevention strategies. People living in rural locations were 3.2 (95% confidence interval: 3.0-3.5) times more likely than urban dwellers to die in road-related incidents, with rates of motor vehicle fatalities universally higher. Common risk factors included drugs and alcohol, speed, driver error and biological sex. Key prevention strategies included improved infrastructure, vehicle design, impaired driving prevention and education. CONCLUSION: Further research regarding preventative measures and significant investment in rural road safety in both Australia and Canada are needed to prevent future incidents.

How the immune system shapes neurodegenerative diseases.

Neurodegenerative diseases are a major cause of death and disability worldwide and are influenced by many factors including age, genetics, and injuries. While these diseases are often thought to result from the accumulation and spread of aberrant proteins, recent studies have demonstrated that they can be shaped by the innate and adaptive immune system. Resident myeloid cells typically mount a sustained response to the degenerating CNS, but peripheral leukocytes such as T and B cells can also alter disease trajectories. Here, we review the sometimes-dichotomous roles played by immune cells during neurodegenerative diseases and explore how brain trauma can serve as a disease initiator or accelerant. We also offer insights into how failure to properly resolve a CNS injury might promote the development of a neurodegenerative disease.

Hyperkalemia in Chronic Kidney Disease: Links, Risks and Management.

Hyperkalemia is a common clinical problem with potentially fatal consequences. The prevalence of hyperkalemia is increasing, partially due to wide-scale utilization of prognostically beneficial medications that inhibit the renin-angiotensin-aldosterone-system (RAASi). Chronic kidney disease (CKD) is one of the multitude of risk factors for and associations with hyperkalemia. Reductions in urinary potassium excretion that occur in CKD can lead to an inability to maintain potassium homeostasis. In CKD patients, there are a variety of strategies to tackle acute and chronic hyperkalemia, including protecting myocardium from arrhythmias, shifting potassium into cells, increasing potassium excretion from the body, addressing dietary intake and treating associated conditions, which may exacerbate problems such as metabolic acidosis. The evidence base is variable but has recently been supplemented with the discovery of novel oral potassium binders, which have shown promise and efficacy in studies. Their use is likely to become widespread and offers another tool to the clinician treating hyperkalemia. Our review article provides an overview of hyperkalemia in CKD patients, including an exploration of relevant guidelines and nuances around management.

Systematic review of the impact of heatwaves on health service demand in Australia.

OBJECTIVES: Heatwaves have been linked to increased levels of health service demand in Australia. This systematic literature review aimed to explore health service demand during Australian heatwaves for hospital admissions, emergency department presentations, ambulance call-outs, and risk of mortality. STUDY DESIGN: A systematic review to explore peer-reviewed heatwave literature published from 2000 to 2020. DATA SOURCES: Articles were reviewed from six databases (MEDLINE, Scopus, Web of Science, PsychINFO, ProQuest, Science Direct). Search terms included: heatwave, extreme heat, ambulance, emergency department, and hospital. Studies were included if they explored heat for a period of two or more consecutive days. Studies were excluded if they did not define a threshold for extreme heat or if they explored data only from workers compensation claims and major events. DATA SYNTHESIS: This review was prospectively registered with PROSPERO (# CRD42021227395 ). Forty-five papers were included in the final review following full-text screening. Following a quality assessment using the GRADE approach, data were extracted to a spreadsheet and compared. Significant increases in mortality, as well as hospital, emergency, and ambulance demand, were found across Australia during heatwave periods. Admissions for cardiovascular, renal, respiratory, mental and behavioural conditions exhibited increases during heatwaves. The most vulnerable groups during heatwaves were children (< 18 years) and the elderly (60+). CONCLUSIONS: Heatwaves in Australia will continue to increase in duration and frequency due to the effects of climate change. Health planning is essential at the community, state, and federal levels to mitigate the impacts of heatwaves on health and health service delivery especially for vulnerable populations. However, understanding the true impact of heatwaves on health service demand is complicated by differing definitions and methodology in the literature. The Excess Heat Factor (EHF) is the preferred approach to defining heatwaves given its consideration of local climate variability and acclimatisation. Future research should explore evidence-based and spatially relevant heatwave prevention programs. An enhanced understanding of heatwave health impacts including service demand will inform the development of such programs which are necessary to promote population and health system resilience.

Road traffic fatalities in rural and remote Australia from 2006 to 2017: The need for targeted action.

OBJECTIVE: To explore rural motor vehicle collision (MVC) fatalities by trends over time, mode of transport, age, state, sex, and Aboriginal and Torres Strait Islander status. DESIGN: A retrospective total population-based time series was conducted using the Australian Bureau of Statistics (ABS) death registration data. SETTING: All statistical local area (SLA) within Australia from 2006 to 2017. PARTICIPANTS: Australian residents whose deaths were registered with the ABS between 01 January 2006 and 31 December 2017 where the underlying cause of death was related to unintentional transport accidents. MAIN OUTCOME MEASURES: Fatality rates were determined using population data collected from the 2006, 2011 and 2016 census. Trends over time by rurality were analysed by financial year. Rates of transport deaths by vehicle type were determined by rurality. Risk ratios were calculated to compare demographic groups based on sex, Aboriginal and Torres Strait Islander status and age. A 3-year scorecard was organised by state and rurality using 99.7% confidence intervals. RESULTS: Motor vehicle collision fatalities increase with increasing remoteness. Females, children from 0 to 14 years, pedestrians, and Aboriginal and Torres Strait Islander peoples are at a significantly higher risk of fatal MVCs than their respective metropolitan counterparts. The 3-year scorecard indicates that road fatality rates in the NT, WA, and all rural and remote areas required immediate attention and targeted action. CONCLUSIONS: There is a need for investment in MVC fatality prevention in rural Australia from inner regional to remote areas in order to meet the road safety targets established by the National Road Safety Strategy.

Glia limitans superficialis oxidation and breakdown promote cortical cell death after repetitive head injury.

Repetitive mild traumatic brain injuries (mTBI) disrupt CNS barriers, the erosion of which has been linked to long-term neurodegenerative and psychiatric conditions. Although much attention has been devoted to CNS vasculature following mTBI, little is known about the glia limitans superficialis - a barrier of surface-associated astrocytes that helps protect the CNS parenchyma and maintain homeostasis. Here, we identify the glia limitans superficialis as a crucial barrier surface whose breakdown after acute repeat mTBI facilitates increased cell death and recruitment of peripheral myelomonocytic cells. Using intravital microscopy, we show that brain-resident microglia fortify this structure after a single mTBI, yet they fail to do so following secondary injury, which triggers massive recruitment of myelomonocytic cells from the periphery that contribute to further destruction of the glia limitans superficialis but not cortical cell death. We demonstrate, instead, that reactive oxygen species (ROS) generated in response to repetitive head injury are largely responsible for enhanced cortical cell death, and therapeutic administration of the antioxidant glutathione markedly reduces this cell death, preserves the glia limitans, and prevents myelomonocytic cells from entering the brain parenchyma. Collectively, our findings underscore the importance of preserving the glia limitans superficialis after brain injury and offer a therapeutic means to protect this structure and the underlying cortex.

Engineered glycomaterial implants orchestrate large-scale functional repair of brain tissue chronically after severe traumatic brain injury.

Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brain's poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery chronically after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely after sTBI significantly enhanced cellular repair and gross motor function recovery when compared to controls 20 weeks after sTBI. Animals subjected to M2 region injuries followed by eCS matrix implantations demonstrated the significant recovery of "reach-to-grasp" function. This was attributed to enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity. These findings indicate that eCS matrices implanted acutely after sTBI can support complex cellular, vascular, and neuronal circuit repair chronically after sTBI.

Chondroitin Sulfate Glycosaminoglycan Matrices Promote Neural Stem Cell Maintenance and Neuroprotection Post-Traumatic Brain Injury.

There are currently no effective treatments for moderate-to-severe traumatic brain injuries (TBIs). The paracrine functions of undifferentiated neural stem cells (NSCs) are believed to play a significant role in stimulating the repair and regeneration of injured brain tissue. We therefore hypothesized that fibroblast growth factor (FGF2) enriching chondroitin sulfate glycosaminoglycan (CS-GAG) matrices can maintain the undifferentiated state of neural stem cells (NSCs) and facilitate brain tissue repair subacutely post-TBI. Rats subjected to a controlled cortical impactor (CCI) induced TBI were intraparenchymally injected with CS-GAG matrices alone or with CS-GAG matrices containing PKH26GL labeled allogeneic NSCs. Nissl staining of brain tissue 4 weeks post-TBI demonstrated the significantly enhanced (p < 0.05) tissue protection in CS-GAG treated animals when compared to TBI only control, and NSC only treated animals. CS-GAG-NSC treated animals demonstrated significantly enhanced (p < 0.05) FGF2 retention, and maintenance of PKH26GL labeled NSCs as indicated by enhanced Sox1+ and Ki67+ cell presence over other differentiated cell types. Lastly, all treatment groups and sham controls exhibited a significantly (p < 0.05) attenuated GFAP+ reactive astrocyte presence in the lesion site when compared to TBI only controls.