First responders' occupational injury and disease associated with periods of extreme bushfires.

There has been limited research on the health impacts of extreme bushfire exposure among emergency responders (ER) involved in suppressing extreme bushfires. This study aimed to evaluate the associations between extreme bushfires and ER's compensated injury and illness in Victoria, Australia. State-wide ER compensation claims from January 2005 to April 2023 were analysed. Logistic regression modelling was used to identify factors associated with compensation claims during the extreme bushfire periods in 2009 and 2019/20, compared to all other claims, adjusting for seasonality (summer). Of the 44,164 included claims, 1105 (2.5%) had recorded injury/disease onset dates within extreme bushfire periods, and 11,642 (26.4%) occurred in summer months. Over half of claims were made by police (52.4%), followed by ambulance officers/paramedics (27.2%) and firefighters (20.5%). Extreme bushfire period claims were associated with older workers (odds ratio/OR = 1.58,95%CI = 1.30-1.92, ages ≥ 55 vs. 35-44 years). Mental disorders (OR = 1.61,95%CI = 1.25-2.07), intracranial injuries (OR = 3.04,95%CI = 1.69-5.48) and infections/parasites (OR = 3.11,95%CI = 1.61-5.98) vs. wounds were associated with extreme bushfire period claims. Given the expected increase in extreme bushfire events and the ageing workforce, study findings underscore the importance of primary and secondary prevention in ER. This can include periodic health surveillance for older workers, access to early treatment, and ongoing support for mental health conditions.

Rationale and Design of the Australasian Registry of Screening ECGs in National Athletes Project.

BACKGROUND: Cardiac screening of elite athletes is widely recommended by Australasian sporting federations, but data are not structured to be shared. Data are lacking from underrepresented groups to inform ECG interpretation guidelines. The ARENA (Australasian Registry of Screening ECGs in National Athletes) project is a retrospective and prospective, multicenter, longitudinal, observational registry of athlete cardiac screening results and outcomes. The aim is to create a repository to improve our understanding of the diagnoses and outcomes of screening. METHODS: Participating sports that conduct cardiac screening of athletes will contribute data. This includes an initial collection (retrospective data, waiver of consent) and future prospective data (opt-out consent). Data include sex, age, sport/event, screening date, ECG findings, cardiac test results, follow-up details, sport participation status, cardiac diagnoses, and major cardiovascular outcomes defined as sudden cardiac arrest/death, cardiac syncope or implanted cardioverter defibrillator shock, cardiac hospitalization, and arrhythmias requiring intervention. Comparisons will be made between diagnoses, outcomes, and ECG features and analyzed by sport and sex. The ARENA project was developed in collaboration with sporting bodies, team physicians, and players association representatives and endorsed by the Australasian College of Sport & Exercise Physicians and Sports Medicine Australia. CONCLUSIONS: The ARENA project will provide a long-term international data repository to improve our understanding of ECG interpretation, cardiac screening and diagnoses, and the prevalence of cardiovascular outcomes in screened athletes. A unique aim is to address evidence gaps in underrepresented athlete groups, specifically female athletes and Indigenous populations. Results will inform screening policies and guidelines.

Current and future burden of Ross River virus infection attributable to increasing temperature in Australia: a population-based study.

Background: Ross River virus (RRV), Australia's most notifiable vector-borne disease transmitted through mosquito bites, has seen increased transmission due to rising temperatures. Quantifying the burden of RRV infection attributable to increasing temperatures (both current and future) is pivotal to inform prevention strategies in the context of climate change. Methods: As RRV-related deaths are rare in Australia, we utilised years lived with disability (YLDs) associated with RRV infection data from the Australian Institute of Health and Welfare (AIHW) Burden of Disease database between 2003 and 2018. We obtained relative risks per 1 °C temperature increase in RRV infection from a previous meta-analysis. Exposure distributions for each Köppen-Geiger climate zone were calculated separately and compared with the theoretical-minimum-risk exposure distribution to calculate RRV burden attributable to increasing temperatures during the baseline period (2003-2018), and projected future burdens for the 2030s and 2050s under two greenhouse gas emission scenarios (Representative Concentration Pathways, RCP 4.5 and RCP 8.5), two adaptation scenarios, and different population growth series. Findings: During the baseline period (2003-2018), increasing mean temperatures contributed to 35.8 (±0.5) YLDs (19.1%) of the observed RRV burden in Australia. The mean temperature attributable RRV burden varied across climate zones and jurisdictions. Under both RCP scenarios, the projected RRV burden is estimated to increase in the future despite adaptation scenarios. By the 2050s, without adaptation, the RRV burden could reach 45.8 YLDs under RCP4.5 and 51.1 YLDs under RCP8.5. Implementing a 10% adaptation strategy could reduce RRV burden to 41.8 and 46.4 YLDs, respectively. Interpretation: These findings provide scientific evidence for informing policy decisions and guiding resource allocation for mitigating the future RRV burden. The current findings underscore the need to develop location-specific adaptation strategies for climate-sensitive disease control and prevention. Funding: Australian Research Council Discovery Program.

Public health and prevention research within the Medical Research Future Fund.

OBJECTIVE: To explore the amount and type of research funded under relevant Medical Research Future Fund (MRFF) Initiatives that addressed public health and prevention from 2018 to July 2023. METHODS: Projects funded by six MRFF Initiatives, with objectives relevant to public health and public health nominated as "field of research" by >25% of applicants, were evaluated against a set of public health research criteria and were categorised based on levels of prevention. RESULTS: Fifty-seven per cent of 249 funded projects were categorised as public health research. Projects with curative features, focusing on tertiary (32%) and quaternary (4%) prevention, were as common as projects with earlier preventive features, focussed on primordial (7%) and primary (28%) prevention. The Preventive and Public Health Research Initiative had the lowest proportion of public health research (48%) of the six evaluated Initiatives and a dominance of curative (39%) and non-preventive (26%) research over preventive research (30%). CONCLUSION: This study highlighted variable levels of public health research across public-health-relevant MRFF Initiatives and generally low proportions of primary and primordial prevention. A greater emphasis on primordial and primary prevention research in public-health-relevant Initiatives could advance prevention in Australia. IMPLICATIONS FOR PUBLIC HEALTH: There appears to be scope for improvement in the prioritisation of upstream prevention research in public-health-relevant MRFF Initiatives and projects. Addressing this may enhance the benefit of MRFF to Australian public health.

Global, regional and national burdens of non-melanoma skin cancer attributable to occupational exposure to solar ultraviolet radiation for 183 countries, 2000-2019: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. METHODS: We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. RESULTS: Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6-1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9-28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7-35.0) for NMSC deaths and 30.4 % (UR 29.0-31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180-19,740) and 0.5 million DALYs (UR 0.4-0.5). Men and older age groups carried larger burden. Over 2000-2019, attributable deaths and DALYs almost doubled. CONCLUSIONS: WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.

Clinical outcomes of 10 years of cardiac screening in elite New Zealand athletes.

OBJECTIVES: To report findings from the High Performance Sport New Zealand cardiac screening programme, including comparisons between sexes and ethnicities. DESIGN: Retrospective cohort study. METHODS: Elite Olympic-sport athletes were screened (2012-2022) with personal/family history, physical examination, resting 12-lead ECG and followed from the date of first screening until July 2022. An audit reviewed screening records, including demographic data, ECGs, follow-up and diagnoses. Flagged/equivocal ECGs were re-reviewed (International Criteria). RESULTS: 2075 ECGs from 1189 athletes (53 % female, mean age 21 years; 83 % European, 9 % Maori, 5 % Pacific Islander, 3 % other) were included. No athletes retired for cardiac reasons; there were no cardiac deaths or major cardiac incidents (mean follow-up from first screening: 6.1 years (range: 0.6-10.9 years)). Diagnoses included Wolff-Parkinson-White (WPW) syndrome (0.7 %) and cardiomyopathies (0.3 %). Overall, 3.5 % of ECGs were abnormal, with ECGs of females more commonly abnormal (4.4 % vs 2.5 %, p = 0.02) and with a higher proportion of ECGs with abnormal T-wave inversion (TWI) (3.1 % vs 0.9 %, p < 0.001) compared to males. Of the abnormal TWI in females (all aged ≥16 years), 47 % was limited to V1-V3 with no other abnormalities. Abnormality rates were similar between Maori, Pacific Islander and European athlete ECGs. CONCLUSIONS: WPW was the most frequent diagnosis, with very little cardiomyopathy found. The proportion of abnormal ECGs was low overall, but higher in females. This was driven by anterior TWI in V1-V3 which was not associated with diagnoses of conditions associated with sudden cardiac death (SCD). There was no difference in the proportion of abnormal ECGs of Maori or Pacific Island athletes compared to European athletes.

The burden of occupational injury attributable to high temperatures in Australia, 2014-19: a retrospective observational study.

OBJECTIVES: To assess the population health impact of high temperatures on workplace health and safety by estimating the burden of heat-attributable occupational injury in Australia. STUDY DESIGN, SETTING: Retrospective observational study; estimation of burden of occupational injury in Australia attributable to high temperatures during 2014-19, based on Safe Work Australia (work-related traumatic injury fatalities and workers' compensation databases) and Australian Institute of Health and Welfare data (Australian Burden of Disease Study and National Hospital Morbidity databases), and a meta-analysis of climate zone-specific risk data. MAIN OUTCOME MEASURE: Burden of heat-attributable occupational injuries as disability-adjusted life years (DALYs), comprising the numbers of years of life lived with disability (YLDs) and years of life lost (YLLs), nationally, by Köppen-Geiger climate zone, and by state and territory. RESULTS: During 2014-19, an estimated 42 884 years of healthy life were lost to occupational injury, comprising 39 485 YLLs (92.1%) and 3399 YLDs (7.9%), at a rate of 0.80 DALYs per 1000 workers per year. A total of 967 occupational injury-related DALYs were attributable to heat (2.3% of occupational injury-related DALYs), comprising 890 YLLs (92%) and 77 YLDs (8%). By climate zone, the heat-attributable proportion was largest in the tropical Am (12 DALYs; 3.5%) and Aw zones (34 DALYs; 3.5%); by state and territory, the proportion was largest in New South Wales and Queensland (each 2.9%), which also included the largest numbers of heat-attributable occupational injury-related DALYs (NSW: 379 DALYs, 39% of national total; Queensland: 308 DALYs; 32%). CONCLUSION: An estimated 2.3% of the occupational injury burden in Australia is attributable to high ambient temperatures. To prevent this burden increasing with global warming, adaptive measures and industry-based policies are needed to safeguard workplace health and safety, particularly in heat-exposed industries, such as agriculture, transport, and construction.

Sheffield Shield Cricketers Live Longer than the Age-Matched General Australian Male Population.

Background/objectives: Previous studies have shown a trend that elite athletes tend to live longer than the general population, which has been attributed to the "healthy worker hire effect" and the health benefits of exercise. There have not been any previous studies looking at survival of elite cricketers with the general population as a reference cohort. This study aimed to compare the annual mortality rates of current and retired elite male Australian cricket players to that of the age-matched general Australian male population. Methods: Analysis of publicly accessible dates of birth, death, and cricket debut data for male Australian Sheffield Shield cricket players who played before 2022 and had not died before 1971. Included persons were Sheffield Shield players who lived primarily in Australia during and after their cricket careers. Death rates from 1971 to 2021 (inclusive) were compared to the general Australian male population. Results: 1824 Sheffield Shield players had not died prior to 1971 (798 had played before the 1971 season, 1026 debuting subsequently). There were 586 deaths in the 51 years of observations, compared to 825 expected deaths, giving a Standardized Mortality Ratio of 0.71 (95% CI 0.63-0.80). Conclusion: Elite Australian male Sheffield Shield cricket players outlive the general male population with lower death rates. This is probably due to a combination of the healthy worker hire effect and the health benefits of exercise. This study provides evidence that in terms of longevity, it is safe to play elite-level cricket in Australia.

Firefighting and Cancer: A Meta-analysis of Cohort Studies in the Context of Cancer Hazard Identification.

Objective: We performed a meta-analysis of epidemiological results for the association between occupational exposure as a firefighter and cancer as part of the broader evidence synthesis work of the IARCMonographs program. Methods: A systematic literature search was conducted to identify cohort studies of firefighters followed for cancer incidence and mortality. Studies were evaluated for the influence of key biases on results. Random-effects meta-analysis models were used to estimate the association between ever-employment and duration of employment as a firefighter and risk of 12 selected cancers. The impact of bias was explored in sensitivity analyses. Results: Among the 16 included cancer incidence studies, the estimated meta-rate ratio, 95% confidence interval (CI), and heterogeneity statistic (I2) for ever-employment as a career firefighter compared mostly to general populations were 1.58 (1.14-2.20, 8%) for mesothelioma, 1.16 (1.08-1.26, 0%) for bladder cancer, 1.21 (1.12-1.32, 81%) for prostate cancer, 1.37 (1.03-1.82, 56%) for testicular cancer, 1.19 (1.07-1.32, 37%) for colon cancer, 1.36 (1.15-1.62, 83%) for melanoma, 1.12 (1.01-1.25, 0%) for non-Hodgkin lymphoma, 1.28 (1.02-1.61, 40%) for thyroid cancer, and 1.09 (0.92-1.29, 55%) for kidney cancer. Ever-employment as a firefighter was not positively associated with lung, nervous system, or stomach cancer. Results for mesothelioma and bladder cancer exhibited low heterogeneity and were largely robust across sensitivity analyses. Conclusions: There is epidemiological evidence to support a causal relationship between occupational exposure as a firefighter and certain cancers. Challenges persist in the body of evidence related to the quality of exposure assessment, confounding, and medical surveillance bias.

Effects of high temperatures and heatwaves on dengue fever: a systematic review and meta-analysis.

BACKGROUND: Studies have shown that dengue virus transmission increases in association with ambient temperature. We performed a systematic review and meta-analysis to assess the effect of both high temperatures and heatwave events on dengue transmission in different climate zones globally. METHODS: A systematic literature search was conducted in PubMed, Scopus, Embase, and Web of Science from January 1990 to September 20, 2022. We included peer reviewed original observational studies using ecological time series, case crossover, or case series study designs reporting the association of high temperatures and heatwave with dengue and comparing risks over different exposures or time periods. Studies classified as case reports, clinical trials, non-human studies, conference abstracts, editorials, reviews, books, posters, commentaries; and studies that examined only seasonal effects were excluded. Effect estimates were extracted from published literature. A random effects meta-analysis was performed to pool the relative risks (RRs) of dengue infection per 1 °C increase in temperature, and further subgroup analyses were also conducted. The quality and strength of evidence were evaluated following the Navigation Guide systematic review methodology framework. The review protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). FINDINGS: The study selection process yielded 6367 studies. A total of 106 studies covering more than four million dengue cases fulfilled the inclusion criteria; of these, 54 studies were eligible for meta-analysis. The overall pooled estimate showed a 13% increase in risk of dengue infection (RR = 1.13; 95% confidence interval (CI): 1.11-1.16, I2 = 98.0%) for each 1 °C increase in high temperatures. Subgroup analyses by climate zones suggested greater effects of temperature in tropical monsoon climate zone (RR = 1.29, 95% CI: 1.11-1.51) and humid subtropical climate zone (RR = 1.20, 95% CI: 1.15-1.25). Heatwave events showed association with an increased risk of dengue infection (RR = 1.08; 95% CI: 0.95-1.23, I2 = 88.9%), despite a wide confidence interval. The overall strength of evidence was found to be "sufficient" for high temperatures but "limited" for heatwaves. Our results showed that high temperatures increased the risk of dengue infection, albeit with varying risks across climate zones and different levels of national income. INTERPRETATION: High temperatures increased the relative risk of dengue infection. Future studies on the association between temperature and dengue infection should consider local and regional climate, socio-demographic and environmental characteristics to explore vulnerability at local and regional levels for tailored prevention. FUNDING: Australian Research Council Discovery Program.

Societal burden of work on injury deaths in New Zealand, 2005-14: An observational study.

Background: Work poses increased risk of injury not only for workers but also for the public, yet the broader impact of work-related injury is not quantified. This study, utilising population data from New Zealand, estimates the societal burden of work-related fatal injury (WRFI) by including bystanders and commuters. Methods: This observational study selected deaths due to unintentional injury, in persons aged 0-84 years using International Classification of Disease external cause codes, matched to coronial records, and reviewed for work-relatedness. Work-relatedness was determined by the decedent's circumstances at the time of the incident: working for pay, profit, in kind, or an unpaid capacity (worker); commuting to or from work (commuter); or a bystander to another's work activity (bystander). To estimate the burden of WRFI, frequencies, percentages, rates, and years-of-life lost (YLL) were estimated. Results: In total 7,707 coronial records were reviewed of which 1,884 were identified as work-related, contributing to 24% of the deaths and 23% of the YLL due to injury. Of these deaths close to half (49%) occurred amongst non-working bystanders and commuters. The overall burden of WRFI was widespread across age, sex, ethnic and deprivation sub-groups. Injury deaths due to machinery (97%) and due to being struck by another object (69%) were predominantly work-related. Interpretation: When utilising a more inclusive definition of work-relatedness the contribution of work to the societal burden of fatal injuries is substantial, conservatively estimated at one quarter of all injury deaths in New Zealand. Other estimates of WRFI likely exclude a similar number of fatalities occurring among commuters and bystanders. The findings, also relevant to other OECD nations, can guide where public health efforts can be used, alongside organisational actions, to reduce WRFI for all those impacted.

Incidence and mortality from malignant mesothelioma 1982-2020 and relationship with asbestos exposure: the Australian Mesothelioma Registry.

OBJECTIVES: Malignant mesothelioma is an uncommon cancer associated with asbestos exposure, predominantly occupational. Asbestos has been banned in Australia since 2003 but mesothelioma has a long latency and incident cases continue to present. The Australian Mesothelioma Registry was incepted to collect systematic data about incidence and mortality alongside asbestos exposure. METHODS: Benefiting from the Australian national system of cancer notification, all incident cases of mesothelioma in all states and territories are fast-tracked and notified regularly. Notified patients are contacted asking for consent to collect exposure information, initially by postal questionnaire and subsequently by telephone interview. Age-standardised annual incidence rates and mortality rates were calculated. Asbestos exposure was categorised as occupational, non-occupational, neither or, both; and as low, or high, probability of exposure. RESULTS: Mesothelioma incidence appears to have peaked. The age-standardised incidence rates have declined steadily since the early 2000s (peaking in males at 5.9/100 000 and in all-persons at 3.2/100 000), driven by rates in males, who comprise the majority of diagnosed cases. Rates in women have remained fairly stable since that time. Age-standardised mortality rates have followed similar trends. Mesothelioma remains the most common in those aged over 80 years. Nearly all (94%) cases were linked with asbestos exposure (78% occupational in men; 6.8% in women). CONCLUSIONS: With effective control of occupational asbestos use, the decline in age-standardised incidence and death rates has occurred. Incidence rates among women, in whom occupational asbestos exposure is rarely detectable, remain unchanged, pointing to the role of household and /or environmental asbestos exposure.

Lessons Learned From Presumptive Condition Lists in Veteran Compensation Systems.

Presumptive condition lists formally accept connections between military factors and veteran health conditions. An environmental scan of such lists and their evidentiary basis was conducted across four veterans' administrations to inform other administrations considering the development of such lists. Information on included conditions, qualifying military factors, and scientific processes was obtained through targeted internet searches and correspondence with veterans' administrations. The content of presumptive condition lists across jurisdictions varied by conditions included, as well as military eligibility requirements (e.g., service in particular conflict, context, or time period). Scientific review processes to develop lists also varied across jurisdictions. Findings indicate that evidence and experience may be leveraged across compensation systems (veteran and civilian). Ongoing research to understand links between military exposures and veteran health is recommended.

Associations between temperature and Ross river virus infection: A systematic review and meta-analysis of epidemiological evidence.

Ross River virus (RRV) infection is one of the emerging and prevalent arboviral diseases in Australia and the Pacific Islands. Although many studies have been conducted to establish the relationship between temperature and RRV infection, there has been no comprehensive review of the association so far. In this study, we performed a systematic review and meta-analysis to assess the effect of temperature on RRV transmission. We searched PubMed, Scopus, Embase, and Web of Science with additional lateral searches from references. The quality and strength of evidence from the included studies were evaluated following the Navigation Guide framework. We have qualitatively synthesized the evidence and conducted a meta-analysis to pool the relative risks (RRs) of RRV infection per 1 °C increase in temperature. Subgroup analyses were performed by climate zones, temperature metrics, and lag periods. A total of 17 studies met the inclusion criteria, of which six were included in the meta-analysis The meta-analysis revealed that the overall RR for the association between temperature and the risk of RRV infection was 1.09 (95% confidence interval (CI): 1.02, 1.17). Subgroup analyses by climate zones showed an increase in RRV infection per 1 °C increase in temperature in humid subtropical and cold semi-arid climate zones. The overall quality of evidence was "moderate" and we rated the strength of evidence to be "limited", warranting additional evidence to reduce uncertainty. The results showed that the risk of RRV infection is positively associated with temperature. However, the risk varies across different climate zones, temperature metrics and lag periods. These findings indicate that future studies on the association between temperature and RRV infection should consider local and regional climate, socio-demographic, and environmental factors to explore vulnerability at local and regional levels.

Impact of legislative reform on worker fatalities in New Zealand workplaces: a 30-year retrospective population-level analysis.

OBJECTIVES: To determine the impact of major legislative changes to New Zealand's Occupational Health and Safety (OHS) legislation with the adoption of the Robens model as a means to control occupational risks on the burden and risk of work-related fatal injury (WRFI). METHODS: Population-based comparison of WRFI to workers aged 15-84 years occurring during three periods: before (pre:1985-1992), after legislative reform (post-1:1993-2002) and after subsequent amendment (post-2:2003-2014). Annual age-industry standardised rates were calculated with 95% CI. Multivariable Poisson regression was used to estimate age-adjusted annual percentage changes (APC) for each period, overall and stratified by high-risk industry and occupational groups. RESULTS: Over the 30-year period, 2053 worker deaths met the eligibility criteria. Age-adjusted APC in rates of worker WRFI changed little between periods: pre (-2.8%, 95% CI 0.0% to -5.5%); post-1 (-2.9%, 95% CI -1.3% to -4.5%) and post-2 (-2.9%, 95% CI -1.3% to -4.4%). There was no evidence of differences in slope. Variable trends in worker WRFI were observed for historically high-risk industry and occupational groups. CONCLUSIONS: The rate of worker WRFI decreased steadily over the 30-year period under examination and there was no evidence that this pattern of declining WRFI was substantially altered with the introduction of Robens-styled OHS legislative reforms. Beyond headline figures, historically high-risk groups had highly variable progress in reducing worker WRFI following legislative reform. This study demonstrates the value in including prereform data and high-risk subgroup analysis when assessing the performance of OHS legislative reforms to control occupational risks.

Next-Generation Sequencing of Minimal Residual Disease for Predicting Relapse after Tisagenlecleucel in Children and Young Adults with Acute Lymphoblastic Leukemia.

We assessed minimal residual disease (MRD) detection and B-cell aplasia after tisagenlecleucel therapy for acute lymphoblastic leukemia (ALL) to define biomarkers predictive of relapse (N = 143). Next-generation sequencing (NGS) MRD detection >0 in bone marrow (BM) was highly associated with relapse. B-cell recovery [signifying loss of functional chimeric antigen receptor (CAR) T cells] within the first year of treatment was associated with a hazard ratio (HR) for relapse of 4.5 [95% confidence interval (CI), 2.03-9.97; P < 0.001]. Multivariate analysis at day 28 showed independent associations of BMNGS-MRD >0 (HR = 4.87; 95% CI, 2.18-10.8; P < 0.001) and B-cell recovery (HR = 3.33; 95% CI, 1.44-7.69; P = 0.005) with relapse. By 3 months, the BMNGS-MRD HR increased to 12 (95% CI, 2.87-50; P < 0.001), whereas B-cell recovery was not independently predictive (HR = 1.27; 95% CI, 0.33-4.79; P = 0.7). Relapses occurring with persistence of B-cell aplasia were largely CD19- (23/25: 88%). Detectable BMNGS-MRD reliably predicts risk with sufficient time to consider approaches to relapse prevention such as hematopoietic cell transplantation (HCT) or second CAR-T cell infusion. SIGNIFICANCE: Detectable disease by BMNGS-MRD with or without B-cell aplasia is highly predictive of relapse after tisagenlecleucel therapy for ALL. Clonotypic rearrangements used to follow NGS-MRD did not change after loss of CD19 or lineage switch. High-risk patients identified by these biomarkers may benefit from HCT or investigational cell therapies.See related commentary by Ghorashian and Bartram, p. 2.This article is highlighted in the In This Issue feature, p. 1.

Value of a national burden-of-disease study: a comparison of estimates between the Australian Burden of Disease Study 2015 and the Global Burden of Disease Study 2017.

BACKGROUND: Estimates of burden of disease are important for monitoring population health, informing policy and service planning. Burden estimates for the same population can be reported differently by national studies [e.g. the Australian Burden of Disease Study (ABDS) and the Global Burden of Disease Study (GBDS)]. METHODS: Australian ABDS 2015 and GBDS 2017 burden estimates and methods for 2015 were compared. Years of life lost (YLL), years lived with disability (YLD) and disability-adjusted life years (DALY) measures were compared for overall burden and 'top 50' causes. Disease-category definitions (based on ICD-10), redistribution algorithms, data sources, disability weights, modelling methods and assumptions were reviewed. RESULTS: GBDS 2017 estimated higher totals than ABDS 2015 for YLL, YLD and DALY for Australia. YLL differences were mainly driven by differences in the allocation of deaths to disease categories and the redistribution of implausible causes of death. For YLD, the main drivers were data sources, severity distributions and modelling strategies. Most top-50 diseases for DALY had a similar YLL:YLD composition reported. CONCLUSIONS: Differences in the ABDS and GBDS estimates reflect the different purposes of local and international studies and differences in data and modelling strategies. The GBDS uses all available evidence and is useful for international comparisons. National studies such as the ABDS have the flexibility to meet local needs and often the advantage of access to unpublished data. It is important that all data sources, inputs and models be assessed for quality and appropriateness. As studies evolve, differences should be accounted for through increased transparency of data and methods.

Examining trajectories of hospital readmission in older adults hospitalised with hip fracture from residential aged care and the community.

Hip fracture trajectories have not been examined for older adults in aged care or living in the community. Trajectories of health care use were defined by distinct predictive factors. These results can inform the development of targeted strategies to reduce health service use following hip fracture. OBJECTIVE: To examine hospital service use trajectories of older adults who were hospitalised for hip fracture and living in a residential aged care facility (RACF) or the community, and to identify factors predictive of trajectory group membership. These findings may inform future programmes aimed at reducing unexpected hospitalisations and subsequently reduce health care costs. METHODS: A group-based trajectory analysis of hospitalisations was conducted for adults aged ≥ 65 years hospitalised for hip fracture during 2008-2009 in New South Wales, Australia. Linked hospitalisation and RACF data were examined for a 5-year period. Group-based trajectory models were derived for RACF and community-dwelling older adults based on the number of subsequent hospital admissions following the index hip fracture. Multinomial logistic regression examined predictors of trajectory group membership for subsequent hospital admissions. RESULTS: There were 5752 hip fracture hospitalisations, with two-thirds of hip fractures occurring in community-dwellers. Key predictors of trajectory group membership for both RACF residents and community-dwellers were age group, sex, hospital length of stay and cognitive impairment. Assistance with activities of daily living and complex health care needs were also predictive of group membership in RACF residents. Location of residence and time to move to a RACF were additional predictors of group membership for community-dwellers. CONCLUSION: Health service use trajectories differed for RACF residents and community-dwellers; however, there were similar patient characteristics that defined trajectory group membership. Low users of hospital services living in RACFs or the community included older adults with generally unfavourable health conditions, potentially indicating that palliative care or advanced care directives and community-care initiatives, respectively, have played a part in the lowered frequency of rehospitalisation.

Non-inferiority of fragmented care for high-risk pediatric neuroblastoma patients: a single institution analysis.

Pediatric neuroblastoma (NB) patients receive multi-modal therapy and may experience care fragmented among multiple institutions with a significant travel burden, which has been associated with poor outcomes for some adult cancers. We hypothesized that fragmented care for pediatric NB patients is associated with inferior outcomes compared to treatment consolidated at one location. We reviewed paper and electronic records for pediatric NB patients who received ≥1 hematopoietic stem cell transplant (HSCT) at Duke from 1990-2017. Fragmented care was defined by treatment at >1 institution and grouped by 2 institutions vs. 3+ institutions. Distances were calculated using Google Maps. To compare all care groups, we used Fisher's Exact and Kruskal-Wallis tests for demographic and treatment characteristics, Kaplan-Meier for unadjusted overall survival (OS), and Cox proportional hazards for factors associated with OS. Of 127 eligible patients, 102 (80.3%) patients experienced fragmented care, with 17 treated at 3+ facilities. Kaplan-Meier analysis did not associate fragmented care with increased mortality (log-rank p = 0.13). With multivariate analysis, only earlier diagnostic decade and greater distance to HSCT remained significantly associated with worsened OS. In this single institutional study, we found fragmented care did not impact overall survival. Worsened overall survival was associated with increased travel distance for HSCT and further research should aim to improve supportive processes for patients undergoing HSCT for high-risk neuroblastoma.