Melbourne School of Population and Global Health - Research Publications

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    Conserved expression patterns predict microRNA targets.
    Ritchie, W ; Rajasekhar, M ; Flamant, S ; Rasko, JEJ ; Ohler, U (Public Library of Science (PLoS), 2009-09)
    microRNAs (miRNAs) are major regulators of gene expression and thereby modulate many biological processes. Computational methods have been instrumental in understanding how miRNAs bind to mRNAs to induce their repression but have proven inaccurate. Here we describe a novel method that combines expression data from human and mouse to discover conserved patterns of expression between orthologous miRNAs and mRNA genes. This method allowed us to predict thousands of putative miRNA targets. Using the luciferase reporter assay, we confirmed 4 out of 6 of our predictions. In addition, this method predicted many miRNAs that act as expression enhancers. We show that many miRNA enhancer effects are mediated through the repression of negative transcriptional regulators and that this effect could be as common as the widely reported repression activity of miRNAs. Our findings suggest that the indirect enhancement of gene expression by miRNAs could be an important component of miRNA regulation that has been widely neglected to date.
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    Beating the blues after Cancer: randomised controlled trial of a tele-based psychological intervention for high distress patients and carers
    Chambers, SK ; Girgis, A ; Occhipinti, S ; Hutchison, S ; Turner, J ; Carter, R ; Dunn, J (BMC, 2009-06-17)
    BACKGROUND: The diagnosis and treatment of cancer is a major life stress such that approximately 35% of patients experience persistent clinically significant distress and carers often experience even higher distress than patients. This paper presents the design of a two arm randomised controlled trial with patients and carers who have elevated psychological distress comparing minimal contact self management vs. an individualised tele-based cognitive behavioural intervention. METHODS/DESIGN: 140 patients and 140 carers per condition (560 participants in total) will been recruited after being identified as high distress through caller screening at two community-based cancer helplines and randomised to 1) a single 30-minute telephone support and education session with a nurse counsellor with self management materials 2) a tele-based psychologist delivered five session individualised cognitive behavioural intervention. Session components will include stress reduction, problem-solving, cognitive challenging and enhancing relationship support and will be delivered weekly. Participants will be assessed at baseline and 3, 6 and 12 months after recruitment. Outcome measures include: anxiety and depression, cancer specific distress, unmet psychological supportive care needs, positive adjustment, overall Quality of life. DISCUSSION: The study will provide recommendations about the efficacy and potential economic value of minimal contact self management vs. tele-based psychologist delivered cognitive behavioural intervention to facilitate better psychosocial adjustment and mental health for people with cancer and their carers. TRIAL REGISTRATION: ACTRN12609000301268.
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    Cost-Effectiveness of Surgically Induced Weight Loss for the Management of Type 2 Diabetes: Modeled Lifetime Analysis
    Keating, CL ; Dixon, JB ; Moodie, ML ; Peeters, A ; Bulfone, L ; Maglianno, DJ ; O'Brien, PE (AMER DIABETES ASSOC, 2009-04-01)
    OBJECTIVE: To estimate the cost-effectiveness of surgically induced weight loss relative to conventional therapy for the management of recently diagnosed type 2 diabetes in class I/II obese patients. RESEARCH DESIGN AND METHODS: This study builds on a within-trial cost-efficacy analysis. The analysis compares the lifetime costs and quality-adjusted life-years (QALYs) between the two intervention groups. Intervention costs were extrapolated based on observed resource utilization during the trial. The proportion of patients in each intervention group with remission of diabetes at 2 years was the same as that observed in the trial. Health care costs for patients with type 2 diabetes and outcome variables required to derive estimates of QALYs were sourced from published literature. A health care system perspective was adopted. Costs and outcomes were discounted annually at 3%. Costs are presented in 2006 Australian dollars (AUD) (currency exchange: 1 AUD = 0.74 USD). RESULTS: The mean number of years in diabetes remission over a lifetime was 11.4 for surgical therapy patients and 2.1 for conventional therapy patients. Over the remainder of their lifetime, surgical and conventional therapy patients lived 15.7 and 14.5 discounted QALYs, respectively. The mean discounted lifetime costs were 98,900 AUD per surgical therapy patient and 101,400 AUD per conventional therapy patient. Relative to conventional therapy, surgically induced weight loss was associated with a mean health care saving of 2,400 AUD and 1.2 additional QALYs per patient. CONCLUSIONS: Surgically induced weight loss is a dominant intervention (it both saves health care costs and generates health benefits) for managing recently diagnosed type 2 diabetes in class I/II obese patients in Australia.
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    Synergy Between Adiposity, Insulin Resistance, Metabolic Risk Factors, and Inflammation in Adolescents
    Huang, R-C ; Mori, TA ; Burke, V ; Newnham, J ; Stanley, FJ ; Landau, LI ; Kendall, GE ; Oddy, WH ; Beilin, LJ (AMER DIABETES ASSOC, 2009-04-01)
    OBJECTIVE: The purpose of this study was to investigate relationships between inflammatory markers and components of a metabolic syndrome cluster in adolescents. RESEARCH DESIGN AND METHODS: This was a cross-sectional analysis of an Australian childhood cohort (n = 1,377) aged 14 years. Cluster analysis defined a "high-risk" group similar to adults with metabolic syndrome. Relevant measures were anthropometry, fasting insulin, glucose, lipids, inflammatory markers, liver function, and blood pressure. RESULTS: Of the children, 29% fell into a high-risk metabolic cluster group compared with 2% by a pediatric metabolic syndrome definition. Relative to the "low-risk" cluster, they had higher BMI (95% CI 19.5-19.8 vs. 24.5-25.4), waist circumference (centimeters) (95% CI 71.0-71.8 vs. 83.4-85.8), insulin (units per liter) (95% CI 1.7-1.8 vs. 3.5-3.9), homeostasis model assessment (95% CI 1.7-1.8 vs. 3.5-3.9), systolic blood pressure (millimeters of mercury) (95% CI 110.8-112.1 vs. 116.7-118.9), and triglycerides (millimoles per liter) (95% CI 0.78-0.80 vs. 1.25-1.35) and lower HDL cholesterol (millimoles per liter) (95% CI 1.44-1.48 vs. 1.20-1.26). Inflammatory and liver function markers were higher in the high-risk group: C-reactive protein (CRP) (P < 0.001), uric acid (P < 0.001), alanine aminotransferase (ALT) (P < 0.001), and gamma-glutamyl transferase (GGT) (P < 0.001). The highest CRP, GGT, and ALT levels were restricted to overweight children in the high-risk group. CONCLUSIONS: Cluster analysis revealed a strikingly high proportion of 14 year olds at risk of cardiovascular disease-related metabolic disorders. Adiposity and the metabolic syndrome cluster are synergistic in the pathogenesis of inflammation. Systemic and liver inflammation in the high-risk cluster is likely to predict diabetes, cardiovascular disease, and nonalcoholic fatty liver disease.
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    Type 2 Diabetes Prevention in the Real World Three-year results of the GOAL Lifestyle Implementation Trial
    Absetz, P ; Oldenburg, B ; Hankonen, N ; Valve, R ; Heinonen, H ; Nissinen, A ; Fogelholm, M ; Talja, M ; Uutela, A (AMER DIABETES ASSOC, 2009-08-01)
    OBJECTIVE We study the effectiveness of the GOAL Lifestyle Implementation Trial at the 36-month follow-up. RESEARCH DESIGN AND METHODS Participants (n = 352, type 2 diabetes risk score FINDRISC = 16.2 +/- 3.3, BMI 32.6 +/- 5.0 kg/m(2)) received six lifestyle counseling sessions over 8 months. Measurements were at baseline, 12 months (88.6%), and 36 months (77.0%). RESULTS Statistically significant risk reduction at 12 months was maintained at 36 months in weight (-1.0 +/- 5.6 kg), BMI (-0.5 +/- 2.1 kg/m(2)), and serum total cholesterol (-0.4 +/- 1.1 mmol/l). CONCLUSIONS Maintenance of risk reduction in this "real world" trial proves the intervention's potential for significant public health impact.
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    Tobacco smoking, body mass index, hypertension, and kidney cancer risk in central and eastern Europe.
    Brennan, P ; van der Hel, O ; Moore, LE ; Zaridze, D ; Matveev, V ; Holcatova, I ; Janout, V ; Kollarova, H ; Foretova, L ; Szeszenia-Dabrowska, N ; Mates, D ; Rothman, N ; Boffetta, P ; Chow, W-H (Springer Science and Business Media LLC, 2008-12-02)
    In a case-control study of kidney cancer in four central European countries, with 1097 incident cases and 1476 controls, we found an increased risk for self-reported hypertension and for obesity. Additional unknown risk factors are likely to be responsible for the high rates of kidney cancer in this region.
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    Risk factors for age-related maculopathy.
    Connell, PP ; Keane, PA ; O'Neill, EC ; Altaie, RW ; Loane, E ; Neelam, K ; Nolan, JM ; Beatty, S (Hindawi Limited, 2009)
    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.
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    Costs and consequences of treatment for mild gestational diabetes mellitus - evaluation from the ACHOIS randomised trial.
    Moss, JR ; Crowther, CA ; Hiller, JE ; Willson, KJ ; Robinson, JS ; Australian Carbohydrate Intolerance Study in Pregnant Women Group, (Springer Science and Business Media LLC, 2007-10-28)
    BACKGROUND: Recommended best practice is that economic evaluation of health care interventions should be integral with randomised clinical trials. We performed a cost-consequence analysis of treating women with mild gestational diabetes mellitus by dietary advice, blood glucose monitoring and insulin therapy as needed compared with routine pregnancy care, using patient-level data from a multi-centre randomised clinical trial. METHODS: Women with a singleton pregnancy who had mild gestational diabetes diagnosed by an oral glucose-tolerance test between 24 and 34 weeks' gestation and their infants were included. Clinical outcomes and outpatient costs derived from all women and infants in the trial. Inpatient costs derived from women and infants attending the hospital contributing the largest number of enrolments (26.1%), and charges to women and their families derived from a subsample of participants from that hospital (in 2002 Australian dollars). Occasions of service and health outcomes were adjusted for maternal age, ethnicity and parity. Analysis of variance was used with bootstrapping to confirm results. Primary clinical outcomes were serious perinatal complications; admission to neonatal nursery; jaundice requiring phototherapy; induction of labour and caesarean delivery. Economic outcome measures were outpatient and inpatient costs, and charges to women and their families. RESULTS: For every 100 women with a singleton pregnancy and positive oral glucose tolerance test who were offered treatment for mild gestational diabetes mellitus in addition to routine obstetric care, $53,985 additional direct costs were incurred at the obstetric hospital, $6,521 additional charges were incurred by women and their families, 9.7 additional women experienced induction of labour, and 8.6 more babies were admitted to a neonatal nursery. However, 2.2 fewer babies experienced serious perinatal complication and 1.0 fewer babies experienced perinatal death. The incremental cost per additional serious perinatal complication prevented was $27,503, per perinatal death prevented was $60,506 and per discounted life-year gained was $2,988. CONCLUSION: It is likely that the general public in high-income countries such as Australia would find reductions in perinatal mortality and in serious perinatal complications sufficient to justify additional health service and personal monetary charges. Over the whole lifespan, the incremental cost per extra life-year gained is highly favourable. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN12606000294550.
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    Weight and place: a multilevel cross-sectional survey of area-level social disadvantage and overweight/obesity in Australia
    King, T ; Kavanagh, AM ; Jolley, D ; Turrell, G ; Crawford, D (NATURE PUBLISHING GROUP, 2006-02-01)
    OBJECTIVE: To estimate variation between small areas in adult body mass index (BMI), and assess the importance of area level socioeconomic disadvantage in predicting BMI. METHODS: We identified all census collector districts (CCDs) in the 20 innermost Local Government Areas in metropolitan Melbourne, Australia, and ranked them by the percentage of low income households (< dollar 400/week). In all, 50 CCDs were randomly selected from the least, middle and most disadvantaged septiles of the ranked list and 4913 residents (61.4% participation rate) completed one of two surveys. Multilevel linear regression was used to estimate area level variance in BMI and the importance of area level socioeconomic disadvantage in predicting BMI. RESULTS: There were significant variations in BMI between CCDs for women, even after adjustment for individual and area SES (P = 0.012); significant area variation was not found for men. Living in the most versus least disadvantaged areas was associated with an average difference in BMI of 1.08 kg/m2 (95% CI: 0.48-1.68 kg/m2) for women, and of 0.93 kg/m2 (95% CI: 0.32-1.55 kg/m2) for men. Living in the mid versus least disadvantaged areas were associated with an average difference in BMI of 0.67 kg/m2 (95% CI: 0.09-1.26 kg/m2) for women, and 0.43 kg/m2 for men (95% CI: -0.16-1.01). CONCLUSION: These findings suggest that area disadvantage is an important predictor of adult BMI, and support the need to focus on improving local environments to reduce socioeconomic inequalities in overweight and obesity.
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    The Quit Benefits Model: a Markov model for assessing the health benefits and health care cost savings of quitting smoking.
    Hurley, SF ; Matthews, JP (Springer Science and Business Media LLC, 2007-01-23)
    BACKGROUND: In response to the lack of comprehensive information about the health and economic benefits of quitting smoking for Australians, we developed the Quit Benefits Model (QBM). METHODS: The QBM is a Markov model, programmed in TreeAge, that assesses the consequences of quitting in terms of cases avoided of the four most common smoking-associated diseases, deaths avoided, and quality-adjusted life-years (QALYs) and health care costs saved (in Australian dollars, A$). Quitting outcomes can be assessed for males and females in 14 five year age-groups from 15-19 to 80-84 years. Exponential models, based on data from large case-control and cohort studies, were developed to estimate the decline over time after quitting in the risk of acute myocardial infarction (AMI), stroke, lung cancer, chronic obstructive pulmonary disease (COPD), and death. Australian data for the year 2001 were sourced for disease incidence and mortality and health care costs. Utility of life estimates were sourced from an international registry and a meta analysis. In this paper, outcomes are reported for simulated subjects followed up for ten years after quitting smoking. Life-years, QALYs and costs were estimated with 0%, 3% and 5% per annum discount rates. Summary results are presented for a group of 1,000 simulated quitters chosen at random from the Australian population of smokers aged between 15 and 74. RESULTS: For every 1,000 males chosen at random from the reference population who quit smoking, there is a an average saving in the first ten years following quitting of A$408,000 in health care costs associated with AMI, COPD, lung cancer and stroke, and a corresponding saving of A$328,000 for every 1,000 female quitters. The average saving per 1,000 random quitters is A$373,000. Overall 40 of these quitters will be spared a diagnosis of AMI, COPD, lung cancer and stroke in the first ten years following quitting, with an estimated saving of 47 life-years and 75 QALYs. Sensitivity analyses indicated that QBM predictions were robust to variations of +/- 10% in parameter estimates. CONCLUSION: The QBM can answer many of the questions posed by Australian policy-makers and health program funders about the benefits of quitting, and is a useful tool to evaluate tobacco control programs. It can easily be re-programmed with updated information or a set of epidemiologic data from another country.