Influenza Vaccine Effectiveness Against Influenza-Related Mortality in Australian Hospitalized Patients: A Propensity Score Analysis.

BACKGROUND: Data on influenza vaccine effectiveness (IVE) against mortality are limited, with no Australian data to guide vaccine uptake. We aimed to assess IVE against influenza-related mortality in Australian hospitalized patients, assess residual confounding in the association between influenza vaccination and mortality, and assess whether influenza vaccination reduces the severity of influenza illness. METHODS: Data were collected between 2010 and 2017 from a national Australian hospital-based sentinel surveillance system using a case-control design. Adults and children admitted to the 17 study hospitals with acute respiratory symptoms were tested for influenza using nucleic acid testing; all eligible test-positive cases, and a subset of test-negative controls, were included. Propensity score analysis and multivariable logistic regression were used to determine the adjusted odds ratio (aOR) of vaccination, with IVE = 1 - aOR × 100%. Residual confounding was assessed by examining mortality in controls. RESULTS: Over 8 seasons, 14038 patients were admitted with laboratory-confirmed influenza. The primary analysis included 9298 cases and 6451 controls, with 194 cases and 136 controls dying during hospitalization. Vaccination was associated with a 31% (95% confidence interval [CI], 3%-51%; P = .033) reduction in influenza-related mortality, with similar estimates in the National Immunisation Program target group. Residual confounding was identified in patients ≥65 years old (aOR, 1.92 [95% CI, 1.06-3.46]; P = .031). There was no evidence that vaccination reduced the severity of influenza illness (aOR, 1.07 [95% CI, .76-1.50]; P = .713). CONCLUSIONS: Influenza vaccination is associated with a moderate reduction in influenza-related mortality. This finding reinforces the utility of the Australian vaccination program in protecting those most at risk of influenza-related deaths.

'Turning the tide' on hyperglycemia in pregnancy: insights from multiscale dynamic simulation modeling.

INTRODUCTION: Hyperglycemia in pregnancy (HIP, including gestational diabetes and pre-existing type 1 and type 2 diabetes) is increasing, with associated risks to the health of women and their babies. Strategies to manage and prevent this condition are contested. Dynamic simulation models (DSM) can test policy and program scenarios before implementation in the real world. This paper reports the development and use of an advanced DSM exploring the impact of maternal weight status interventions on incidence of HIP. METHODS: A consortium of experts collaboratively developed a hybrid DSM of HIP, comprising system dynamics, agent-based and discrete event model components. The structure and parameterization drew on a range of evidence and data sources. Scenarios comparing population-level and targeted prevention interventions were simulated from 2018 to identify the intervention combination that would deliver the greatest impact. RESULTS: Population interventions promoting weight loss in early adulthood were found to be effective, reducing the population incidence of HIP by 17.3% by 2030 (baseline ('business as usual' scenario)=16.1%, 95% CI 15.8 to 16.4; population intervention=13.3%, 95% CI 13.0 to 13.6), more than targeted prepregnancy (5.2% reduction; incidence=15.3%, 95% CI 15.0 to 15.6) and interpregnancy (4.2% reduction; incidence=15.5%, 95% CI 15.2 to 15.8) interventions. Combining targeted interventions for high-risk groups with population interventions promoting healthy weight was most effective in reducing HIP incidence (28.8% reduction by 2030; incidence=11.5, 95% CI 11.2 to 11.8). Scenarios exploring the effect of childhood weight status on entry to adulthood demonstrated significant impact in the selected outcome measure for glycemic regulation, insulin sensitivity in the short term and HIP in the long term. DISCUSSION: Population-level weight reduction interventions will be necessary to 'turn the tide' on HIP. Weight reduction interventions targeting high-risk individuals, while beneficial for those individuals, did not significantly impact forecasted HIP incidence rates. The importance of maintaining interventions promoting healthy weight in childhood was demonstrated.

Cardiac procedures in ST-segment-elevation myocardial infarction - the influence of age, geography and Aboriginality.

BACKGROUND: Timely restoration of bloodflow acute ST-segment elevation myocardial infarction (STEMI) reduces myocardial damage and improves prognosis. The objective of this study was describe the association of demographic factors with hospitalisation rates for STEMI and time to angiography, Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Graft (CABG) in New South Wales (NSW) and the Australian Capital Territory (ACT), Australia. METHODS: This was an observational cohort study using linked population health data. We used linked records of NSW and the ACT hospitalisations and the Australian Government Medicare Benefits Schedule (MBS) for persons aged 35 and over hospitalised with STEMI in the period 1 July 2010 to 30 June 2014. Survival analysis was used to determine the time between STEMI admission and angiography, PCI and CABG, with a competing risk of death without cardiac procedure. RESULTS: Of 13,117 STEMI hospitalisations, 71% were among males; 55% were 65-plus years; 64% lived in major cities, and 2.6% were Aboriginal people. STEMI hospitalisation occurred at a younger age in males than females. Angiography and PCI rates decreased with age: angiography 69% vs 42% and PCI 60% vs 34% on day 0 for ages 35-44 and 75-plus respectively. Lower angiography and PCI rates and higher CABG rates were observed outside major cities. Aboriginal people with STEMI were younger and more likely to live outside a major city. Angiography, PCI and CABG rates were similar for Aboriginal and non-Aboriginal people of the same age and remoteness area. CONCLUSIONS: There is a need to improve access to definitive revascularisation for STEMI among appropriately selected older patients and in regional areas. Aboriginal people with STEMI, as a population, are disproportionately affected by access to definitive revascularisation outside major cities. Improving access to timely definitive revascularisation in regional areas may assist in closing the gap in cardiovascular outcomes between Aboriginal and non-Aboriginal people.

The impact of new universal child influenza programs in Australia: Vaccine coverage, effectiveness and disease epidemiology in hospitalised children in 2018.

BACKGROUND: New jurisdictionally-based vaccination programs were established providing free quadrivalent influenza vaccine (QIV) for preschool Australian children in 2018. This was in addition to the National Immunisation Program (NIP) funded QIV for Indigenous children and children with comorbid medical conditions. We assessed the impact of this policy change on influenza disease burden and vaccine coverage, as well as report on 2018 vaccine effectiveness in a hospital-based surveillance system. METHODS: Subjects were recruited prospectively from twelve PAEDS-FluCAN sentinel hospital sites (April until October 2018). Children aged ≤16 years hospitalised with an acute respiratory illness (ARI) and laboratory-confirmed influenza were considered cases. Hospitalised children with ARI who tested negative for influenza were considered controls. VE estimates were calculated from the adjusted odds ratio of vaccination in cases and controls. RESULTS: A total of 458 children were hospitalised with influenza: 31.7% were <2 years, 5.0% were Indigenous, and 40.6% had medical comorbidities predisposing to severe influenza. Influenza A was detected in 90.6% of children (A/H1N1: 38.0%; A/H3N2: 3.1%; A/unsubtyped 48.6%). The median length of stay was 2 days (IQR: 1,3) and 8.1% were admitted to ICU. Oseltamivir use was infrequent (16.6%). Two in-hospital deaths occurred (0.45%). 12.0% of influenza cases were vaccinated compared with 36.0% of test-negative controls. Vaccine effectiveness of QIV for preventing influenza hospitalisation was estimated at 78.8% (95%CI: 66.9; 86.4). CONCLUSIONS: Compared with 2017 (n = 1268 cases), a significant reduction in severe influenza was observed in Australian children, possibly contributed to by improved vaccine coverage and high vaccine effectiveness. Despite introduction of jurisdictionally-funded preschool programs and NIP-funded vaccine for children with risk factors for severe disease, improved coverage is required to ensure adequate protection against paediatric influenza morbidity and mortality.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2018: the Influenza Complications Alert Network (FluCAN).

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2018 influenza season. In this observational surveillance system, cases were defined as patients admitted to any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data were also collected on a frequency-matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 3 April to 31 October 2018 (the 2018 influenza season), 769 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 30% were elderly (≥65 years), 28% were children (<16 years), 6.4% were Aboriginal and Torres Strait Islander peoples, 2.2% were pregnant and 66% had chronic comorbidities. A small proportion of FluCAN admissions were due to influenza B (13%). Estimated vaccine coverage was 77% in the elderly (≥65 years), 45% in non-elderly adults with medical comorbidities and 26% in children (<16 years) with medical comorbidities. The estimated vaccine effectiveness (VE) in the target population was 52% (95% CI: 37%, 63%). There were a smaller number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2018 than in 2017, with the demographic profile reflecting the change in circulating subtype from A/H3N2 to A/H1N1.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2017: the Influenza Complications Alert Network (FluCAN).

The Influenza Complications Alert Network (FluCAN) is a sentinel-hospital-based surveillance program that operates at sites in all jurisdictions in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2017 influenza season. In this observational surveillance system, cases were defined as patients admitted to any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data are also collected on a frequency-matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 3 April to 31 October 2017 (the 2017 influenza season), 4,359 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 52% were elderly (≥65 years), 14% were children (<16 years), 6.5% were Aboriginal and Torres Strait Islander peoples, 1.6% were pregnant and 78% had chronic comorbidities. A significant proportion were due to influenza B (31%). Estimated vaccine coverage was 72% in the elderly (≥65 years), 50% in non-elderly adults with medical comorbidities and 24% in children (<16 years) with medical comorbidities. The estimated vaccine effectiveness (VE) in the target population was 23% (95% CI: 7%, 36%). There were a large number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2017, with case numbers more than twice that reported in 2016.

Turning conceptual systems maps into dynamic simulation models: An Australian case study for diabetes in pregnancy.

BACKGROUND: System science approaches are increasingly used to explore complex public health problems. Quantitative methods, such as participatory dynamic simulation modelling, can mobilise knowledge to inform health policy decisions. However, the analytic and practical steps required to turn collaboratively developed, qualitative system maps into rigorous and policy-relevant quantified dynamic simulation models are not well described. This paper reports on the processes, interactions and decisions that occurred at the interface between modellers and end-user participants in an applied health sector case study focusing on diabetes in pregnancy. METHODS: An analysis was conducted using qualitative data from a participatory dynamic simulation modelling case study in an Australian health policy setting. Recordings of participatory model development workshops and subsequent meetings were analysed and triangulated with field notes and other written records of discussions and decisions. Case study vignettes were collated to illustrate the deliberations and decisions made throughout the model development process. RESULTS: The key analytic objectives and decision-making processes included: defining the model scope; analysing and refining the model structure to maximise local relevance and utility; reviewing and incorporating evidence to inform model parameters and assumptions; focusing the model on priority policy questions; communicating results and applying the models to policy processes. These stages did not occur sequentially; the model development was cyclical and iterative with decisions being re-visited and refined throughout the process. Storytelling was an effective strategy to both communicate and resolve concerns about the model logic and structure, and to communicate the outputs of the model to a broader audience. CONCLUSION: The in-depth analysis reported here examined the application of participatory modelling methods to move beyond qualitative conceptual mapping to the development of a rigorously quantified and policy relevant, complex dynamic simulation model. The analytic objectives and decision-making themes identified provide guidance for interpreting, understanding and reporting future participatory modelling projects and methods.

Influenza Epidemiology, Vaccine Coverage and Vaccine Effectiveness in Children Admitted to Sentinel Australian Hospitals in 2017: Results from the PAEDS-FluCAN Collaboration.

BACKGROUND: In 2017, Australia experienced record influenza notifications. Two surveillance programs combined to summarize the epidemiology of hospitalized influenza in children and report on vaccine effectiveness (VE) in the context of a limited nationally funded vaccination program. METHODS: Subjects were prospectively recruited (April-October 2017). Case patients were children aged ≤16 years admitted to 11 hospitals with an acute respiratory illness and laboratory-confirmed influenza. Controls were hospitalized with acute respiratory illness and tested negative for influenza. VE estimates were calculated using the test-negative design. RESULTS: A total of 1268 children were hospitalized with influenza: 31.5% were <2 years old, 8.3% were indigenous, and 45.1% had comorbid conditions predisposing to severe influenza. Influenza B was detected in 34.1% with influenza A/H1N1 and A/H3N2 detected in 47.2% and 52.8% of subtyped influenza A specimens. The median length of stay was 3 days (interquartile range, 1-5), 14.5% were admitted to the intensive care unit, and 15.9% received oseltamivir. Four in-hospital deaths occurred (0.3%): one was considered influenza associated. Only 17.1% of test-negative-controls were vaccinated. The VE of inactivated quadrivalent influenza vaccine for preventing hospitalized influenza was estimated at 30.3% (95% confidence interval, 2.6%-50.2%). CONCLUSIONS: Significant influenza-associated morbidity was observed in 2017 in Australia. Most hospitalized children had no comorbid conditions. Vaccine coverage and antiviral use was inadequate. Influenza vaccine was protective in 2017, yet VE was lower than previous seasons. Multiple Australian states have introduced funded preschool vaccination programs in 2018. Additional efforts to promote vaccination and monitor effectiveness are required.

Decision makers' experience of participatory dynamic simulation modelling: methods for public health policy.

BACKGROUND: Systems science methods such as dynamic simulation modelling are well suited to address questions about public health policy as they consider the complexity, context and dynamic nature of system-wide behaviours. Advances in technology have led to increased accessibility and interest in systems methods to address complex health policy issues. However, the involvement of policy decision makers in health-related simulation model development has been lacking. Where end-users have been included, there has been limited examination of their experience of the participatory modelling process and their views about the utility of the findings. This paper reports the experience of end-user decision makers, including senior public health policy makers and health service providers, who participated in three participatory simulation modelling for health policy case studies (alcohol related harm, childhood obesity prevention, diabetes in pregnancy), and their perceptions of the value and efficacy of this method in an applied health sector context. METHODS: Semi-structured interviews were conducted with end-user participants from three participatory simulation modelling case studies in Australian real-world policy settings. Interviewees were employees of government agencies with jurisdiction over policy and program decisions and were purposively selected to include perspectives at different stages of model development. RESULTS: The 'co-production' aspect of the participatory approach was highly valued. It was reported as an essential component of building understanding of the modelling process, and thus trust in the model and its outputs as a decision-support tool. The unique benefits of simulation modelling included its capacity to explore interactions of risk factors and combined interventions, and the impact of scaling up interventions. Participants also valued simulating new interventions prior to implementation in the real world, and the comprehensive mapping of evidence and its gaps to prioritise future research. The participatory aspect of simulation modelling was time and resource intensive and therefore most suited to high priority complex topics with contested options for intervening. CONCLUSION: These findings highlight the value of a participatory approach to dynamic simulation modelling to support its utility in applied health policy settings.

Building the Machine: The Importance of Governance in Obesity Policy.

The Australian Capital Territory (ACT) is a small Australian jurisdiction with a single tier of government and a population of approximately 400,000 people. Despite enjoying comparatively high levels of income, education, physical amenity, and access to nutritious food, overweight and obesity is the most prevalent risk factor for chronic disease in the ACT. From 2011, the ACT Government Health Directorate (ACT Health) led the development of a whole of Government plan (the Action Plan) to address obesity. A political imperative to take such action and recent administrative reform assisted the development of a plan with specific actions to be undertaken by different government agencies. Obesity is a "wicked problem" with a diversity of opinion about its causes and potential solutions. These opinions remained influential even when an official course of action had been decided upon. Strong decision making and accountability processes were therefore necessary to support the development of the Action Plan. A lack of understanding beyond the health sector in relation to the evidence for effective, population level interventions to address obesity and a tendency to try and address population health risks by scaling up client-centered models of Government services also proved problematic. This experience highlights the critical importance of designing obesity policy within a robust governance framework in order to ensure progress is made in a highly contested environment. Whilst the observations included here are strongly influenced by local contextual factors, there are important lessons which can be applied elsewhere.

Retinoic acid elicits a coordinated expression of gut homing markers on T lymphocytes of Zambian men receiving oral Vivotif, but not Rotarix, Dukoral or OPVERO vaccines.

All-trans retinoic acid (ATRA) up-regulates, in laboratory animals, the expression of the gut homing markers α4ß7 integrin and CCR9 on lymphocytes, increasing their gut tropism. Here, we show that, in healthy adult volunteers, ATRA induced an increase of these gut homing markers on T cells in vivo in a time dependent manner. The coordinated increase of α4ß7 and CCR9 by ATRA was seen in 57% (12/21) of volunteers and only when given together with an oral Vivotif vaccine. When this coordinated response to ATRA and Vivotif vaccine was present, it was strongly correlated with the gut immunoglobulin A (IgA) specific response to vaccine LPS (ρ = 0.82; P = 0.02). Using RNA-Seq analysis of whole blood transcription, patients receiving ATRA and Vivotif in conjunction showed transcriptomic changes in immune-related pathways, particularly including interferon α/ß signaling pathway, membrane-ECM interactions and immune hubs. These results suggest that exogenous ATRA can be used to manipulate responses to a subclass of oral vaccines, so far limited to a live attenuated Vivotif vaccine.

Dynamic CT Scan of the Normal Scapholunate Joint in a Clenched Fist and Radial and Ulnar Deviation.

BACKGROUND: Injuries to the scapholunate can have severe long-term effects on the wrist. Early detection of these injuries can help identify pathology. The purpose of this study was to evaluate the motions of the scapholunate joint in normal wrists in a clenched fist and through radial and ulnar deviation using novel dynamic computed tomography (CT) imaging. METHODS: Fifteen participants below 40 years of age consented to have their wrist scanned. Eight participants were randomized to have the right wrist scanned and 7 the left wrist. Volunteers were positioned at the back of the gantry with the wrist placed on the table, palmar side down. Participants began with the hand in a relaxed fist position and then proceeded through an established range of motion protocol. Dynamic CT imaging was captured throughout the range of motion. RESULTS: The movement in the healthy scapholunate joint through a clenched fist and radial and ulnar deviation is minimal. The averages were 1.19, 1.01, and 0.95 mm, representing the middle, dorsal, and volar measurements, respectively. CONCLUSIONS: This novel dynamic CT scan of the wrist is a user-friendly way of measuring of the scapholunate distance, which is minimal in the normal wrist below 40 years of age.

School-based systems change for obesity prevention in adolescents: outcomes of the Australian Capital Territory 'It's Your Move!'

OBJECTIVE: The Australian Capital Territory 'It's Your Move!' (ACT-IYM) was a three-year (2012-2014) systems intervention to prevent obesity among adolescents. METHODS: The ACT-IYM project involved three intervention schools and three comparison schools and targeted secondary students aged 12-16 years. The intervention consisted of multiple initiatives at individual, community, and school policy level to support healthier nutrition and physical activity. Intervention school-specific objectives related to increasing active transport, increasing time spent physically active at school, and supporting mental wellbeing. Data were collected in 2012 and 2014 from 656 students. Anthropometric data were objectively measured and behavioural data self-reported. RESULTS: Proportions of overweight or obesity were similar over time within the intervention (24.5% baseline and 22.8% follow-up) and comparison groups (31.8% baseline and 30.6% follow-up). Within schools, two of three the intervention schools showed a significant decrease in the prevalence of overweight and obesity (p<0.05). CONCLUSIONS: There was some evidence of effectiveness of the systems approach to preventing obesity among adolescents. Implications for public health: The incorporation of systems thinking has been touted as the next stage in obesity prevention and public health more broadly. These findings demonstrate that the use of systems methods can be effective on a small scale.

Repeated Vaccination Does Not Appear to Impact Upon Influenza Vaccine Effectiveness Against Hospitalization With Confirmed Influenza.

BACKGROUND.: Annual influenza vaccine is recommended for those at greatest risk of severe influenza infection. Recent reports of a negative impact of serial influenza vaccination on vaccine effectiveness (VE) raises concerns about the recommendation for annual influenza vaccines, particularly in persons at greatest risk. METHODS.: The Influenza Complications Alert Network (FluCAN) is an Australian hospital-based sentinel surveillance program. In this observational study, cases were defined as subjects aged >9 years admitted with influenza confirmed by polymerase chain reaction. Controls were subjects with acute respiratory illness testing negative for influenza. Propensity scores were used to adjust for the likelihood of being vaccinated. VE was calculated as 1 - adjusted odds ratio of vaccination in cases compared with test-negative controls. RESULTS.: Over 2010-2015, 6223 cases and 6505 controls were hospitalized with confirmed influenza and influenza test-negative acute respiratory illness, respectively. Following stratification by quintile of propensity score, site, and year, VE was estimated to be 43% (95% confidence interval [CI], 37%-49%) overall. VE was estimated to be 51% (95% CI, 45%-57%) in those vaccinated in both the current and previous season, compared with 33% (95% CI, 17%-47%) vaccinated in the current season only and 35% (95% CI, 21%-46%) in the previous season only. Similar results were observed for influenza A/H1N1, influenza A/H3N2, and influenza B strains. CONCLUSIONS.: Vaccination in both the current and previous seasons was associated with a higher VE against hospitalization with influenza than vaccination in either single season. These findings reinforce current recommendations for annual influenza vaccination, particularly those at greatest risk of influenza disease.

Evaluating and Using Observational Evidence: The Contrasting Views of Policy Makers and Epidemiologists.

BACKGROUND: Currently, little is known about the types of evidence used by policy makers. This study aimed to investigate how policy makers in the health domain use and evaluate evidence and how this differs from academic epidemiologists. By having a better understanding of how policy makers select, evaluate, and use evidence, academics can tailor the way in which that evidence is produced, potentially leading to more effective knowledge translation. METHODS: An exploratory mixed-methods study design was used. Quantitative measures were collected via an anonymous online survey (n = 28), with sampling from three health-related government and non-government organizations. Semi-structured interviews with policy makers (n = 20) and epidemiologists (n = 6) were conducted to gather qualitative data. RESULTS: Policy makers indicated systematic reviews were the preferred research resource (19%), followed closely by qualitative research (16%). Neither policy makers nor epidemiologists used grading instruments to evaluate evidence. In the web survey, policy makers reported that consistency and strength of evidence (93%), the quality of data (93%), bias in the evidence (79%), and recency of evidence (79%) were the most important factors taken into consideration when evaluating the available evidence. The same results were found in the qualitative interviews. Epidemiologists focused on the methodology used in the study. The most cited barriers to using robust evidence, according to policy makers, were political considerations (60%), time limitations (55%), funding (50%), and research not being applicable to current policies (50%). CONCLUSION: The policy maker's investigation did not report a systematic approach to evaluating evidence. Although there was some overlap between what policy makers and epidemiologists identified as high-quality evidence, there was also some important differences. This suggests that the best scientific evidence may not routinely be used in the development of policy. In essence, the policy-making process relied on other jurisdictions' policies and the opinions of internal staff members as primary evidence sources to inform policy decisions. Findings of this study suggest that efforts should be directed toward making scientific information more systematically available to policy makers.