Healthcare professionals' experiences and perceptions of artificial intelligence in regional and rural health districts in Australia.

INTRODUCTION: A greater understanding of Australian healthcare professionals' perceptions of artificial intelligence (AI) is needed to identify the challenges ahead as this new technology finds its way into healthcare delivery. OBJECTIVE: The aim of this study was to identify healthcare professionals' perceptions of AI, their understanding of this technology, their education needs and barriers they perceived to its implementation. DESIGN: Healthcare professionals in eight local health districts in New South Wales Australia were surveyed using the Shinners Artificial Intelligence Perception (SHAIP) tool. FINDINGS: The study surveyed 176 participants from regional (59.5%), rural (36.4%) and metropolitan (4.0%) healthcare districts in Australia. Only 27% of all participants stated they are currently using AI in the delivery of care. The study found that Age, Discipline, Use of AI and Desire for Education had a significant effect on perceptions of AI, and that overall healthcare professionals believe AI will impact their role and they do not feel prepared for its use. The study showed that understanding of AI is varied and workforce knowledge is seen as the greatest barrier to implementation. More than 75% of healthcare professionals desire education about AI, its application and ethical implications to the delivery of care. CONCLUSION: The development of education is needed urgently to prepare healthcare professionals for the implementation of AI.

Patterns of emergency department use in rural and metropolitan New South Wales by socioeconomic status: A population-based study.

OBJECTIVE: To investigate the patterns of ED use in metropolitan and rural New South Wales (NSW) by socioeconomic status (SES). METHODS: We undertook a retrospective, population-based study of de-identified data from the NSW Emergency Department Data Collection (EDDC). The study population comprised of NSW residents who presented to an NSW public hospital ED in 2013-2019 and were registered in the NSW EDDC. Total ED presentations, negative binomial regression modelled annual changes in ED presentations over 2013-2019, and age- and sex-standardised rates of ED presentations in 2019 were assessed. RESULTS: Overall, between 2013 and 2019, ED presentations increased in metropolitan and rural NSW, with mean annual percentage increases of 3.1% (95% confidence interval [CI] 2.8-3.5) and 2.5% (95% CI 2.0-2.9), respectively. This growth varied by SES, with larger increases observed in higher SES groups. The bulk of presentations in rural NSW were from individuals living in disadvantaged areas. Standardised rates of ED presentations were highest in the most disadvantaged quintiles (SES 1) and progressively decreased with increasing SES in both rural and metropolitan NSW (negative gradients). Rates were higher in rural NSW compared to metropolitan NSW across all SES quintiles for total, low acuity and non-low acuity presentations. CONCLUSIONS: Negative gradients in rates of ED presentations with increasing SES were observed in both metropolitan and rural NSW. At each SES quintile, rates of ED presentations were higher in rural compared to metropolitan areas. Further research exploring the underlying causal mechanisms leading to increased ED demand in rural NSW and socioeconomically disadvantaged populations is warranted.

Australian nurses' and midwives' perceptions of their workplace environment during the COVID-19 pandemic.

Background: Working as a front-line worker during a pandemic is a unique situation that requires a supportive work environment. An informed understanding of nurses' and midwives' workplace experiences during a pandemic, such as COVID-19, may enable better preparation and targeted support for future pandemics at an individual, organisational, and policy level. Aim: The aim of this study was to explore nurses' and midwives' workplace experiences during the COVID-19 pandemic response. Methods: A cross-sectional online survey consisting of open-ended questions was conducted with a convenience sample of nurses and midwives (n = 1003) working in New South Wales Health hospital settings, in Australia. Open-ended questions were analysed using content analysis. Results: Five themes were identified; 'organisational communication', 'workplace support', 'availability of personal protective equipment', 'flexible working', and 'new ways of working'. Nurses' and midwives' workplace experiences during COVID-19 were influenced by leaders who were perceived to be adaptive, authentic, responsive, transparent, and visible. While many expressed a number of workplace challenges, including access to personal protective equipment, there was opportunity to explore, develop, and evaluate new and alternate models of care and working arrangements. Conclusion: It is important that nurses and midwives are supported and well prepared to cope during pandemics in the workplace. Organisational leadership and timely dissemination of transparent pandemic plans may support nurses' adaptive workplace experiences.

A ‘joint’ approach: design, implementation and preliminary outcomes of an early conservative knee and hip osteoarthritis service in northern New South Wales, Australia.

Australia is facing a growing burden of knee and hip osteoarthritis (OA). To address this demand in northern New South Wales, a community health-based conservative OA joint management service was established in the Tweed Valley. This paper describes the design, implementation and initial evaluation of the service. Following the principles of clinical redesign, a diagnostic phase involving consultation with key stakeholders revealed several issues. OA patients could wait up to 9 months for review by orthopaedic specialist following GP referral and received limited information on how to conservatively manage their conditions. GPs were constrained by short consultations and had limited knowledge of the latest recommendations for the conservative treatment of OA. GPs also highlighted the limitations of outdated fax systems for communication, noting their preference for secure electronic messaging. Based on these findings, the Tweed Knee and Hip Arthritis Service was established. For patients not on a waiting list for surgery, the service provides evidence-based conservative management for knee or hip OA involving standardised assessment, education, exercise, self-management strategies and regular review. An analysis of a foundational cohort of patients demonstrated improvements in a suite of validated and standardised measures for pain and function, with improvements seen as early as 1 month and sustained for 6 months. The study findings support the introduction of integrated conservative OA management models of care directly available to primary healthcare providers.

Exploring healthcare professionals' perceptions of artificial intelligence: Piloting the Shinners Artificial Intelligence Perception tool.

OBJECTIVE: There is an urgent need to prepare the healthcare workforce for the implementation of artificial intelligence (AI) into the healthcare setting. Insights into workforce perception of AI could identify potential challenges that an organisation may face when implementing this new technology. The aim of this study was to psychometrically evaluate and pilot the Shinners Artificial Intelligence Perception (SHAIP) questionnaire that is designed to explore healthcare professionals' perceptions of AI. Instrument validation was achieved through a cross-sectional study of healthcare professionals (n = 252) from a regional health district in Australia. METHODS AND RESULTS: Exploratory factor analysis was conducted and analysis yielded a two-factor solution consisting of 10 items and explained 51.7% of the total variance. Factor one represented perceptions of 'Professional impact of AI' (α = .832) and Factor two represented 'Preparedness for AI' (α = .632). An analysis of variance indicated that 'use of AI' had a significant effect on healthcare professionals' perceptions of both factors. 'Discipline' had a significant effect on Allied Health professionals' perception of Factor one and low mean scale score across all disciplines suggests that all disciplines perceive that they are not prepared for AI. CONCLUSIONS: The results of this study provide preliminary support for the SHAIP tool and a two-factor solution that measures healthcare professionals' perceptions of AI. Further testing is needed to establish the reliability or re-modelling of Factor 2 and the overall performance of the SHAIP tool as a global instrument.

The impact of COVID-19 pandemic-related stress experienced by Australian nurses.

Globally, the impact of COVID-19 on healthcare workers' mental health has been a major focus of recent research. However, Australian research involving nurses, particularly across the acute care sector, is limited. This cross-sectional research aimed to explore the impact of pandemic-related stress on psychological adjustment outcomes and potential protective factors for nurses (n = 767) working in the Australian acute care sector during the COVID-19 pandemic. Nurses completed an online questionnaire with psychometrically validated measures of pandemic-related stress, psychological adjustment outcomes (depression, anxiety, and subjective well-being), and protective factors (posttraumatic growth and self-compassion). Descriptive analyses revealed that pandemic-related stress was reported by 17.7% of the participants. Psychological adjustment outcome scores above normal for depression (27.5%) and anxiety (22.0%) were found, and 36.4% of the participants reported poor subjective well-being. Regression analyses suggest that pandemic-related stress predicted greater depression (B = 0.32, SE = 0.02, 95% confidence interval [0.28, 0.35]) and anxiety (B = 0.26, SE = 0.01, 95% confidence interval [0.24, 0.29]) and less subjective well-being (B = -0.14, SE = 0.01, 95% confidence interval [-0.16, -0.12]). Self-compassion weakened the relationship between pandemic-related stress and greater depression, however, exacerbated the relationship between pandemic-related stress and less subjective well-being. Posttraumatic growth reduced the negative relationship between pandemic-related stress and psychological adjustment outcomes. These findings will inform strategies to facilitate psychological resources that support nurses' psychological adjustment, enabling better pandemic preparedness at both an individual and organizational level.

Cardiovascular risk factor mediation of the effects of education and Genetic Risk Score on cardiovascular disease: a prospective observational cohort study of the Framingham Heart Study.

OBJECTIVES: Level of education and genetic risk are key predictors of cardiovascular disease (CVD). While several studies have explored the causal mechanisms of education effects, it remains uncertain to what extent genetic risk is mediated by established CVD risk factors. This study sought to investigate this and explored the mediation of education and genetic effects on CVD by established cardiovascular risk factors in the Framingham Heart Study (FHS). DESIGN: Prospective observational cohort study. PARTICIPANTS: 7017 participants from the FHS. SETTING: Community-based cohort of adults in Framingham, Massachusetts, USA. PRIMARY OUTCOME MEASURE: Incident CVD. The total effects of education and genetic predisposition using a 63-variant genetic risk score (GRS) on CVD, as well as those mediated by established CVD risk factors, were assessed via mediation analysis based on the counterfactual framework using Cox proportional hazards regression models. RESULTS: Over a median follow-up time of 12.0 years, 1091 participants experienced a CVD event. Education and GRS displayed significant associations with CVD after adjustment for age and sex and the established risk factors smoking, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), body mass index, systolic blood pressure (SBP) and diabetes. For education effects, smoking, HDL-C and SBP were estimated to mediate 18.8% (95% CI 9.5% to 43%), 11.5% (95% CI 5.7% to 29.0%) and 4.5% (95% CI 1.6% to 13.3%) of the total effect of graduate degree, respectively, with the collective of all risk factors combined mediating 38.5% (95% 24.1% to 64.9%). A much smaller proportion of the effects of GRS were mediated by established risk factors combined (17.6%, 95% CI 2.4% to 35.7%), with HDL-C and TC mediating 11.5% (95% CI 6.2% to 21.5%) and 3.1% (95% CI 0.2% to 8.3%), respectively. CONCLUSIONS: Unlike education inequalities, established risk factors mediated only a fraction of GRS effects on CVD. Further research is required to elucidate the underlying causal mechanisms of genetic contributions to CVD.

'The ethics approval took 20 months on a trial which was meant to help terminally ill cancer patients. In the end we had to send the funding back': a survey of views on human research ethics reviews.

BACKGROUND: We conducted a survey to identify what types of health/medical research could be exempt from research ethics reviews in Australia. METHODS: We surveyed Australian health/medical researchers and Human Research Ethics Committee (HREC) members. The survey asked whether respondents had previously changed or abandoned a project anticipating difficulties obtaining ethics approval, and presented eight research scenarios, asking whether these scenarios should or should not be exempt from ethics review, and to provide (optional) comments. Qualitative data were analysed thematically; quantitative data in R. RESULTS: We received 514 responses. Forty-three per cent of respondents to whom the question applied, reported changing projects in anticipation of obstacles from the ethics review process; 25% reported abandoning projects for this reason. Research scenarios asking professional staff to provide views in their area of expertise were most commonly exempted from ethics review (to prioritise systematic review topics 84%, on software strengths/weaknesses 85%); scenarios involving surplus samples (82%) and N-of-1 (single case) studies (76%) were most commonly required to undergo ethics review. HREC members were 26% more likely than researchers to require ethics review. Need for independent oversight, and low risk, were most frequently cited in support of decisions to require or exempt from ethics review, respectively. CONCLUSIONS: Considerable differences exist between researchers and HREC members, about when to exempt from review the research that ultimately serves the interests of patients and the public. It is widely accepted that evaluative research should be used to reduce clinical uncertainties-the same principle should apply to ethics reviews.

Patterns of emergency department use in rural and metropolitan New South Wales from 2012 to 2018.

OBJECTIVE: To explore the patterns of and investigate the factors associated with rises in emergency department presentations in rural and metropolitan New South Wales from 2012 to 2018. DESIGN: A retrospective descriptive study of de-identified data from the New South Wales Emergency Department Data Collection. SETTING: New South Wales, Australia. PARTICIPANTS: All individuals presenting to 99 New South Wales emergency departments, which continuously reported to the Emergency Department Data Collection between 2012 and 2018. A total of 2 166 449 presentations recorded throughout New South Wales in 2012 (rural 786 278; metropolitan 1 380 171) and 2 477 192 in 2018 (rural 861 761; metropolitan 1 615 431). MAIN OUTCOME MEASURES: Total emergency department presentations, plus Poisson regression modelled annual changes in emergency department presentations over the period 2012-2018. RESULTS: Growth in emergency department presentations outpaced population growth in both rural and metropolitan New South Wales between 2012 and 2018. The patterns of age-standardised rates of presentations were broadly similar between rural and metropolitan areas, with highest rates observed in the youngest (0-4 years) and oldest (85+ years) cohorts. The rural sample also displayed a distinct third peak in ages 15-39 years, and rates were higher across all age groups. Rural New South Wales displayed disproportionately higher emergency department presentations in the two most deprived socio-economic status quintiles. While rural New South Wales displayed significant reductions in triage category 5 (non-urgent cases) over time, the relative proportion remained approximately double that of metropolitan sites. CONCLUSIONS: There are differences between rural and metropolitan emergency department presentations relating to demographic factors, triage levels, acuity and admissions. Detailed local investigations are required to determine specific contextual issues that impact on emergency department demand.

Mind the gap: is it time to invest in embedded researchers in regional, rural and remote health services to address health outcome discrepancies for those living in rural, remote and regional areas?

Research capacity building in healthcare works to generate and apply new knowledge to improve health outcomes; it creates new career pathways, improves staff satisfaction, retention and organisational performance. While there are examples of investment and research activity in rural Australia, overall, rural research remains under-reported, undervalued and under-represented in the evidence base. This is particularly so in primary care settings. This lack of contextual knowledge generation and translation perpetuates rural-metropolitan health outcome disparities. Through greater attention to and investment in building research capacity and capability in our regional, rural and remote health services, these issues may be partially addressed. It is proposed that it is time for Australia to systematically invest in rurally focussed, sustainable, embedded research capacity building.

Impact of emergency department occupancy on waiting times, rates of admission and representation, and length of stay when hospitalised: A data linkage study.

OBJECTIVES: To assess the association between ED occupancy and relevant outcomes including ED waiting times, rates of admission and representation and length of stay when hospitalised. METHODS: Retrospective study of all ED presentations by New South Wales (NSW), Australia, residents to 15 NSW public, principal referral or paediatric specialist hospitals between 1 January to 31 December 2015 (N = 935 282). ED data were linked longitudinally (to ED data) and cross-sectionally to hospital admissions data. An ED-system measure of occupancy was assigned to each ED record. The study outcomes were ED waiting time, admission to hospital, 28 day representation, and length of stay (LOS) when admitted. Outcomes were analysed using univariate analyses and multivariable general linear and binary logistic regression models. RESULTS: Increased ED occupancy was associated with increased ED waiting times, particularly at low-baseline occupancy (e.g. rate ratio = 2.22, 95% confidence interval [CI] [2.10-2.35], for non-urgent triaged patients). However, results were conditional on triage category, such that estimated effects were smaller or not significant in emergency and resuscitation triaged patients (e.g. rate ratio = 1.59, 95% CI [1.52-1.65], for emergency patients). ED occupancy only showed small or no associations with admission to hospital, 28 day representation and LOS when admitted. CONCLUSIONS: Higher ED occupancy was associated with increased waiting times conditional on triage category and baseline occupancy. Collectively, the results show that NSW principal referral EDs are robust, and are currently capable of handling variation in occupancy by prioritising treatment for the most urgent patients.

Utility of metabolic profiling of serum in the diagnosis of pregnancy complications.

INTRODUCTION: Currently there are no clinical screening tests available to identify pregnancies at risk of developing preeclampsia (PET) and/or intrauterine growth restriction (IUGR), both of which are associated with abnormal placentation. Metabolic profiling is now a stable analytical platform used in many laboratories and has successfully been used to identify biomarkers associated with various pathological states. METHODS: We used nuclear magnetic resonance spectroscopy (NMR) to metabolically profile serum samples collected from 143 pregnant women at 26-41 weeks gestation with pregnancy outcomes of PET, IUGR, PET IUGR or small for gestational age (SGA) that were age-matched to normal pre/term pregnancies. RESULTS: Spectral analysis found no difference in the measured metabolites from normal term, pre-term and SGA samples, and of 25 identified metabolites, only glutamate was marginally different between groups. Of the identified metabolites, 3-methylhistidine, creatinine, acetyl groups and acetate, were determined to be independent predictors of PET and produced area under the curves (AUC) = 0.938 and 0.936 for the discovery and validation sets. Only 3-hydroxybutyrate was determined to be an independent predictor of IUGR, however the model had low predictive power (AUC = 0.623 and 0.581 for the discovery and validation sets). CONCLUSIONS: A sub-panel of metabolites had strong predictive power for identifying PET samples in a validation dataset, however prediction of IUGR was more difficult using the identified metabolites. NMR based metabolomics can identify metabolites strongly associated with disease and has the potential to be useful in developing early clinical screening tests for at risk pregnancies.

Age and cause-of-death contributions to area socioeconomic, sex and remoteness differences in life expectancy in New South Wales, 2010-2012.

OBJECTIVES: To determine age group- and cause-of-death-specific contributions to area socioeconomic status (SES), sex and remoteness life expectancy inequalities. METHODS: Mortality and estimated residential population data from New South Wales, Australia, over 2010-2012 was used to calculate life expectancy. Inequalities by sociodemographic groups were partitioned into age group- and cause-of-death-specific contributions. RESULTS: The largest contributions to SES differentials in life expectancy were observed at 60-84 years of age; for cancer, cardiovascular, endocrine and respiratory causes of death; and additionally external causes of death for males. Sex inequalities ranged from 3.6 to 5.2 years, with common causes of death such as cardiovascular disease and cancer in late adulthood (60+ years) accounting for the bulk of the differences. Smaller differences in life expectancy were observed by remoteness, with the largest contributions observed in ages 85 years and above, and for cardiovascular, mental, cancer and external causes of death. CONCLUSIONS: Common causes of death in late adulthood accounted for the bulk of life expectancy inequalities. Implications for public health: Development of policy and interventions aimed at addressing social determinants, such as proposed by the WHO's Global Plan of Action, are needed to help reduce sociodemographic inequalities in lifespan.

Patterns of low acuity patient presentations to emergency departments in New South Wales, Australia.

OBJECTIVE: To explore the patterns of low acuity patient (LAP) presentations to EDs in New South Wales (NSW), Australia. METHODS: Retrospective study of NSW public hospital ED presentations between January 2013 and December 2014 that were registered in the NSW Emergency Department Data Collection (n = 409 035). LAPs were defined according to the Australian Institute of Health and Welfare (AIHW), Sprivulis and multiple ACEM methods. Multivariable logistic regression was used to assess the adjusted odds of LAP ED presentation by a suite of sociodemographic factors. RESULTS: The percentage of LAPs varied considerably by definition, being as high as 54.7% (inner regional areas) and as low as 3.2% (major cities) using revised ACEM methods modified to contain unlimited consultation times or consultation times of 15 min or less, respectively. For each method, higher proportions of LAPs were observed in inner regional and remote/very remote areas relative to major cities. LAP ED presentations, based on ACEM definition with 1 h or 15 min consultation times, were greater in younger patients, increased during out of business hours and weekends, and decreased with increasing general practitioner (GP) density. CONCLUSION: The percentage of LAPs varied substantially by definition, and further work is required to validate the methods, particularly around the appropriateness of length of consultation time with ACEM, between different hospitals and remoteness areas. Age was strongly associated with low acuity, with substantial effects also observed for GP density, and attendances during out of hours and weekends.

Socioeconomic, remoteness and sex differences in life expectancy in New South Wales, Australia, 2001-2012: a population-based study.

OBJECTIVES: Despite being one of the healthiest countries in the world, Australia displays substantial mortality differentials by socioeconomic disadvantage, remoteness and sex. In this study, we examined how these mortality differentials translated to differences in life expectancy between 2001 and 2012. DESIGN AND SETTING: Population-based study using mortality and estimated residential population data from Australia's largest state, New South Wales (NSW), between 2001 and 2012. Age-group-specific death rates by socioeconomic disadvantage quintile, remoteness (major cities vs regional and remote areas), sex and year were estimated via Poisson regression, and inputted into life table calculations to estimate life expectancy. RESULTS: Life expectancy decreased with increasing socioeconomic disadvantage in males and females. The disparity between the most and least socioeconomically deprived quintiles was 3.77 years in males and 2.39 years in females in 2012. Differences in life expectancy by socioeconomic disadvantage were mostly stable over time. Gender gaps in life expectancy ranged from 3.50 to 4.93 years (in 2012), increased with increasing socioeconomic disadvantage and decreased by ∼1 year for all quintiles between 2001 and 2012. Overall, life expectancy varied little by remoteness, but was 1.8 years higher in major cities compared to regional/remote areas in the most socioeconomically deprived regions in 2012. CONCLUSIONS: Socioeconomic disadvantage and sex were strongly associated with life expectancy. The disparity in life expectancy across the socioeconomic spectrum was larger in males and was stable over time. In contrast, gender gaps reduced for all quintiles between 2001 and 2012, and a remoteness effect was evident in 2012, but only for those living in the most deprived areas.

Association of Gestational Age and Severe Neonatal Morbidity with Mortality in Early Childhood.

BACKGROUND: Although infant and child mortality rates have decreased substantially worldwide over the past two decades, efforts continue in many nations to further these declines. The identification of pertinent perinatal factors that are associated with early childhood mortality would help with these efforts. We investigated the association of two crucial perinatal factors, gestational age and severe neonatal morbidity at birth, with mortality during infancy (29-364 days) and early childhood (1-5 years). METHODS: The study population included all singleton livebirths, ≥32 weeks' gestation in New South Wales, Australia in 2001-11. Birth data were linked to hospitalisation morbidity data and deaths data (linked birth cohort n = 871 916), and multivariable Cox regression models were used to assess mortality. RESULTS: The median follow-up time per child was 4.95 years (range 0.00-5.92 years; 3 614 738 total person-years), with 984 deaths observed. Gestational age was associated with increased mortality, and specifically from deaths attributable to infections, respiratory conditions, and injuries during infancy, but not during early childhood. Severe neonatal morbidity strongly mediated the effects of gestational age during infancy, but not during early childhood, and was associated with increased mortality from circulatory, nervous, and respiratory system causes. CONCLUSIONS: The direct effects of gestational age on mortality extended up to 1 year of age, whereas severe neonatal morbidity remained associated with heightened mortality into early childhood. Efforts to maximise the health and well-being of vulnerable infants, with emphasis on preventing infections and injuries, may help further reduce early childhood mortality.

Survival, Hospitalization, and Acute-Care Costs of Very and Moderate Preterm Infants in the First 6 Years of Life: A Population-Based Study.

OBJECTIVES: To investigate survival, hospitalization, and acute-care costs of very (28-31 weeks' gestation) and moderate preterm (32-33 weeks' gestation) infants in the first 6 years of life and compare outcomes with the more widely studied extremely preterm infants (24-27 weeks' gestation) and to full term (low risk) infants (39-40 weeks' gestation). STUDY DESIGN: Birth data from all women residing in New South Wales, Australia, with gestational ages between 24-33 and 39-40 weeks in 2001-2011 were linked probabilistically to hospitalization and mortality data. Study outcomes were evaluated with the use of descriptive and multivariable analyses at birth (N = 559,532), discharge (N = 540,240), and at 1 (N = 487,447) and 6 years of age (N = 230,498). RESULTS: Mortality was greatest among extremely preterm infants (eg, 31.2% within 6 years) and decreased with increasing gestational age. Likewise, hospitalization within the first year of life increased with decreasing gestational age (aOR 5.5 [95% CI 4.7-6.4], 3.7 [3.4-4.0], and 2.6 [2.5-2.8] for birth at 24-27, 28-31, and 32-33 weeks' gestation, relative to 39-40 weeks' gestation). Hospitalization remained significantly increased with preterm birth at each year of age up to 6 years (aORs 1.3-1.6 at 6 years). Cumulative costs were significantly greater with preterm birth within the first year of life, and also between 1 and 6 years of age. CONCLUSIONS: The risks of adverse health outcomes were significantly greater in very and moderately preterm infants relative to full term infants but lower than extremely preterm infants. Crucially, preterm birth was associated with prolonged increased odds of hospitalization (up to age 6 years), contributing to greater resource use.

Development of a potent melanoma vaccine capable of stimulating CD8(+) T-cells independently of dendritic cells in a mouse model.

At present, there are no vaccines approved for the prevention or treatment of malignant melanoma, despite the amount of time and resources that has been invested. In this study, we aimed to develop a self-contained vaccine capable of directly stimulating anticancer CD8(+) T-cell immune responses. To achieve this, three whole-cell melanoma vaccines were developed expressing 4-1BBL or B7.1 T-cell co-stimulatory molecules individually or in combination. The ability of engineered vaccine cell lines to stimulate potent anticancer immune responses in C57BL/6 mice was assessed. Mice vaccinated with cells overexpressing both 4-1BBL and B7.1 (B16-F10-4-1BBL-B7.1-IFNγ/ß anticancer vaccine) displayed the greatest increases in CD8(+) T-cell populations (1.9-fold increase versus control within spleens), which were efficiently activated following antigenic stimulation, resulting in a 10.7-fold increase in cancer cell cytotoxicity relative to control. The enhanced immune responses in B16-F10-4-1BBL-B7.1-IFNγ/ß-vaccinated mice translated into highly efficient rejection of live tumour burdens and conferred long-term protection against repeated tumour challenges, which were likely due to enhanced effector memory T-cell populations. Similar results were observed when dendritic cell (DC)-deficient LTα(-/-) mice were treated with the B16-F10-4-1BBL-B7.1-IFNγ/ß anticancer vaccine, suggesting that the vaccine can directly stimulate CD8(+) T-cell responses in the context of severely reduced DCs. This study shows that the B16-F10-4-1BBL-B7.1-IFNγ/ß anticancer vaccine acted as a highly effective antigen-presenting cell and is likely to be able to directly stimulate CD8(+) T-cells, without requiring co-stimulatory signals from either CD4(+) T-cells or DCs, and warrants translation of this technology into the clinical setting.

Hospitalisations from 1 to 6 years of age: effects of gestational age and severe neonatal morbidity.

BACKGROUND: To investigate whether the adverse infant health outcomes associated with early birth and severe neonatal morbidity (SNM) persist beyond the first year of life and impact on paediatric hospitalisations for children up to 6 years of age. METHODS: The study population included all singleton live births, >32 weeks gestation in New South Wales, Australia, in 2001-2005, with follow-up to 6 years of age. Birth data were probabilistically linked to hospitalisation data (n = 392 964). The odds of hospitalisation, mean hospital length of stay (LOS) and costs, and cumulative LOS were evaluated by gestational age and SNM using multivariable analyses. RESULTS: A total of 74 341 (18.9%) and 41 404 (10.5%) infants were hospitalised once and more than once, respectively. SNM was associated with increased odds of hospitalisation once (adjusted odds ratio [aOR] 1.16 [95% confidence interval 1.10, 1.22]) and more than once [aOR 1.51 (1.43, 1.61)]. Decreasing gestational age was associated with increasing odds of hospitalisation more than once from aOR 1.19 at 37-38 weeks to 1.49 at 33-34 weeks. Average LOS and costs per hospital admission were increased with SNM but not with decreasing gestational age. Cumulative LOS was significantly increased with SNM and decreasing gestational age. CONCLUSIONS: Adverse effects of SNM and early birth persist between 1 and 6 years of age. Strategies to prevent early birth and reduce SNM, and to increase health monitoring of vulnerable infants throughout childhood may help reduce paediatric hospitalisations.