Utilising data for a better understanding of disease

The Australian health system is awash with data. Across our primary and public healthcare systems we are collecting data through administrative systems, medical records, and pathology laboratories, to name just a few. These data have been used by researchers and policy makers, but there remains much to be gained from harnessing new technologies and linking datasets to better inform our understanding of disease. In this thesis, I present four pieces of work on topics that are united through their use of data linkage or new technology. Throughout my four years as a Master of Philosophy in Applied Epidemiology (MAE) scholar I undertook a variety of work in conjunction with four field placement organisations: Apunipima Cape York Health Council, the National Aboriginal Community Controlled Health Organisation, the Hunter New England local hospitals district, and Queensland Health. This thesis presents the results of the applied research from these organisations. My first project is an epidemiological study on early childhood growth in Cape York communities from 1999-2010. By combining routinely collected data on child weights with birth data from the National Perinatal Epidemiology and Statistics Unit we demonstrated a relationship between birth weight and early childhood growth. We also highlighted that while significant improvements have been made in early childhood growth, there remained high rates of low birth weight and prematurity. My second project is an evaluation of the National Key Performance Indicators for Aboriginal and Torres Strait Islander Primary Health Care Services (nKPIs). This collection is the first attempt by the Australian Government to use data extracted from clinical records to monitor the effectiveness of the health system. Our evaluation assessed the quality and usability of the 24 indicators that comprise the nKPIs. While these data have great potential, our evaluation highlighted that they also have important limitations, such as the biases introduced when using these data for population health indicators like smoking status. My third project is a data analysis of Staphylococcus aureus isolates in the Hunter New England region from 2008-2014. This region has established a dataset of patient demographics and hospitalisations that we combined with laboratory data on S. aureus isolates. By combining these data we demonstrated a high proportion of methicillin resistant S. aureus (MRSA) that primarily occurred within young people with no recent exposure to the public healthcare system. This study highlights that control measures for MRSA must move from the hospital into the community setting. My final project is a report on an outbreak investigation of Salmonella Saintpaul that I conducted on behalf of Queensland Health in March 2015. We conducted hypothesis-generating interviews with 23 cases and while our investigation did not reveal a source of the outbreak, analysis with further typing raised the possibility that the increase in reported cases was not in fact an outbreak. This raises the importance of characterisation of Salmonella with genetic tests to identify common strains. My thesis demonstrates the possibilities available through data linkage and molecular characterisation as we move into a new era of public health

Socioeconomic variation in absolute cardiovascular disease risk and treatment in the Australian population

Cardiovascular disease (CVD), preventable through appropriate management of absolute CVD risk, disproportionately affects socioeconomically disadvantaged individuals. The aim of this study was to estimate absolute and relative socioeconomic inequalities in absolute CVD risk and treatment in the Australian population using cross-sectional representative data on 4,751 people aged 45-74 from the 2011-12 Australian Health Survey. Poisson regression was used to calculate prevalence differences (PD) and ratios (PR) for prior CVD, high 5-year absolute risk of a primary CVD event and guideline-recommended medication use, in relation to socioeconomic position (SEP, measured by education). After adjusting for age and sex, the prevalence of high absolute risk of a primary CVD event among those of low, intermediate and high SEP was 12.6%, 10.9% and 7.7% (PD, low vs. high=5.0 [95% CI: 2.3, 7.7], PR=1.6 [1.2, 2.2]) and for prior CVD was 10.7%, 9.1% and 6.7% (PD=4.0 [1.4, 6.6], PR=1.6 [1.1, 2.2]). The proportions using preventive medication use among those with high primary risk were 21.3%, 19.5% and 29.4% for low, intermediate and high SEP and for prior CVD, were 37.8%, 35.7% and 17.7% (PD=20.1 [9.7, 30.5], PR=2.1 [1.3, 3.5]). Proportions at high primary risk and not using medications among those of low, intermediate and high SEP were 10.6%, 8.8% and 4.7% and with prior CVD not using medications were 8.5%, 6.3% and 4.1%. Findings indicate substantial potential to prevent CVD and reduce inequalities through appropriate management of high absolute risk in the population.This work was supported by a National Health and Medical Research Council of Australia (NHMRC) Partnership Project (reference 1092674) and the NHMRC Centre for Research Excellence in Medicines and Ageing (reference 1060407). Emily Banks is supported by the NHMRC (reference 1042717)

Understanding the structure and processes of primary health care for young indigenous children

INTRODUCTION: Primary health care organisations need to continuously reform to more effectively address current health challenges, particularly for vulnerable populations. There is growing evidence that optimal health service structures are essential for producing positive outcomes. AIM: To determine if there is an association between process of care indicators (PoCIs) for important young indigenous child health and social issues and: (i) primary health-care service and child characteristics; and (ii) organisational health service structures. METHODS: This was a cross-sectional study of 1554 clinical child health audits and associated system assessments from 74 primary care services from 2012 to 2014. Composite PoCIs were developed for social and emotional wellbeing, child neurodevelopment and anaemia. Crude and adjusted logistic regression models were fitted, clustering for health services. Odds ratios and 95% confidence intervals were derived. RESULTS: Overall, 32.0% (449) of records had a social and emotional wellbeing PoCI, 56.6% (791) had an anaemia PoCI and 49.3% (430) had a child neurodevelopment PoCI. Children aged 12–23 months were significantly more likely to receive all PoCIs compared to children aged 24–59 months. For every one point increase in assessment scores for team structure and function (aOR 1.14, 95% CI 1.01–1.27) and care planning (aOR 1.14, 95% CI 1.01–1.29) items, there was a 14% greater odds of a child having an anaemia PoCI. Social and emotional wellbeing and child neurodevelopment PoCIs were not associated with system assessment scores. DISCUSSION: Ensuring young indigenous children aged 24–59 months are receiving quality care for important social and health indicators is a priority. Processes of care and organisational systems in primary care services are important for the optimal management of anaemia in indigenous children

Aboriginal and Torres Strait Islander absolute cardiovascular risk assessment and management: systematic review of evidence to inform national guidelines

Australia’s absolute cardiovascular disease (CVD) risk assessment algorithm1 first examines whether individuals meet criteria for clinically determined high CVD risk and, in those not meeting these criteria, applies the Framingham Risk Equation to estimate an individual’s risk of having a CVD event in the next 5 years. The same risk equation is used for Aboriginal and Torres Strait Islander people and non-Indigenous Australians, although there is variation in underlying risk across the two populations, with the former experiencing a greater burden of cardiovascular risk factors.This research was funded by a grant from the Australian Government Department of Health

General practitioners' perspectives on the prevention of cardiovascular disease: systematic review and thematic synthesis of qualitative studies

Objective Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally, and prevention of CVD is a public health priority. This paper aims to describe the perspectives of general practitioners (GPs) on the prevention of CVD across different contexts. Design Systematic review and thematic synthesis of qualitative studies using the Enhancing Transparency of Reporting the Synthesis of Qualitative research (ENTREQ) framework. Data sources MEDLINE, Embase, PsycINFO and CINAHL from database inception to April 2018. Eligibility criteria for selecting studies We included qualitative studies on the perspectives of GPs on CVD prevention. Data extraction and synthesis We used HyperRESEARCH to code the primary papers and identified themes. Results We selected 34 studies involving 1223 participants across nine countries. We identified six themes: defining own primary role (duty to prescribe medication, refraining from risking patients’ lives, mediating between patients and specialists, delegating responsibility to patients, providing holistic care); trusting external expertise (depending on credible evidence and opinion, entrusting care to other health professionals, integrating into patient context); motivating behavioural change for prevention (highlighting tangible improvements, negotiating patient acceptance, enabling autonomy and empowerment, harnessing the power of fear, disappointment with futility of advice); recognising and accepting patient capacities (ascertaining patient’s drive for lifestyle change, conceding to ingrained habits, prioritising urgent comorbidities, tailoring to patient environment and literacy); avoiding overmedicalisation (averting long-term dependence on medications, preventing a false sense of security, minimising stress of sickness) and minimising economic burdens (avoiding unjustified costs to patients, delivering practice within budget, alleviating healthcare expenses). Conclusions GPs sought to empower patients to prevent CVD, but consideration of patients’ individual factors was challenging. Community-based strategies for assessing CVD risk involving other health professionals, and decision aids that address the individuality of the patient’s health and environment, may support GPs in their decisions regarding CVD prevention. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial.The work was supported by a National Health and Medical Research Council of Australia Partnership Grant (1092674), including support from the National Heart Foundation of Australia. AT is supported by a NHMRC Fellowship (1106716)

Review of evidence for the alignment of guidelines on Aboriginal and Torres Strait Islander absolute cardiovascular disease risk: A report prepared for the Australian Government Department of Health

Policy context: Cardiovascular disease (CVD) is highly preventable. CVD continues to be the largest contributor to mortality within the Aboriginal and Torres Strait Islander population and rates of CVD are disproportionately higher within the Australian Aboriginal and Torres Strait Islander population compared to the non-Indigenous population. Improving uptake of current evidence based solutions such as the absolute risk approach to CVD within the Aboriginal and Torres Strait Islander population is important to address this disparity. Although there are several tools available supporting an absolute CVD risk approach, clinical uptake is limited due to a number of factors including an outdated continued reliance on the ‘single risk factor’ approach to prevention, diagnosis and treatment of CVD. A major barrier to uptake is inconsistent messages in the current clinical practice guidelines. Key messages: There are three main guidelines on the absolute CVD risk approach for Aboriginal and Torres Strait Islander peoples in Australia: The NVDPA Guidelines for the Management of Absolute Cardiovascular Disease Risk; The Central Australian Rural Practitioners Association Standard Treatment Manual; and the RACGP National Guide to a Preventive Health Assessment for Aboriginal and Torres Strait Islander People. There is considerable alignment between the existing guidelines, including the need for an absolute risk approach, conditions conferring automatic high risk, use of the Framingham risk equation as the basis of calculating absolute risk, and the need to treat people at a greater than 15% risk of a primary CVD event over the next five years. The guidelines diverge materially in relation to four recommendations: 1) the age at which to commence absolute CVD risk assessment; 2) whether or not calculated risk scores should be adjusted upward by 5%; 3) how often CVD risk should be assessed; and 4) treatment targets for blood pressure. Available evidence indicates that CVD events and high absolute CVD risk occurs earlier in Aboriginal and Torres Strait Islander peoples, and that prevention of CVD should also start early. The proportion of Aboriginal and Torres Strait Islander peoples at high absolute CVD risk at the ages of 18-34 years broadly corresponds to the proportion at high risk among the general population aged 45-54 years. Limited evidence suggests that the current risk scores are likely to underestimate risk in Aboriginal and Torres Strait Islander peoples. Specific data on the extent of underestimation and alternative validated risk scores in this population are lacking. There is no primary data on adjusting risk scores upwards by 5% in Aboriginal and Torres Strait Islander people. Frequency of CVD risk assessment should be based on initial level of risk but the optimal interval for risk reassessment at each level of risk is not clear. There is general agreement between the guidelines to lower blood pressure as tolerated but there are inconsistencies in the exact blood pressure target. Evidence suggests that reductions in systolic blood pressure result in proportional reductions in CVD events and all-cause mortality. CVD guidelines could be kept up to date by adopting a ‘living’ guidelines model, but consideration needs to be given to how to identify relevant updated evidence and how to integrate the updates into electronic decision support tools.This research was supported by a grant from the Australian Government Department of Health

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance