Cost-Effectiveness of Pharmacotherapy to Reduce Obesity

Aims: Obesity causes a high disease burden in Australia and across the world. We aimed to analyse the cost-effectiveness of weight reduction with pharmacotherapy in Australia, and to assess its potential to reduce the disease burden due to excess body weight

Five genetic variants associated with prostate cancer

The increasing availability of whole-genome sequence data is expected to increase the accuracy of genomic prediction. However, results from simulation studies and analysis of real data do not always show an increase in accuracy from sequence data compared to high-density (HD) single nucleotide polymorphism (SNP) chip genotypes. In addition, the sheer number of variants makes analysis of all variants and accurate estimation of all effects computationally challenging. Our objective was to find a strategy to approximate the analysis of whole-sequence data with a Bayesian variable selection model. Using a simulated dataset, we applied a Bayes R hybrid model to analyse whole-sequence data, test the effect of dropping a proportion of variants during the analysis, and test how the analysis can be split into separate analyses per chromosome to reduce the elapsed computing time. We also investigated the effect of imputation errors on prediction accuracy. Subsequently, we applied the approach to a dataset that contained imputed sequences and records for production and fertility traits for 38,492 Holstein, Jersey, Australian Red and crossbred bulls and cows

A generic model for the assessment of disease epidemiology: the computational basis of DisMod II

Epidemiology as an empirical science has developed sophisticated methods to measure the causes and patterns of disease in populations. Nevertheless, for many diseases in many countries only partial data are available. When the partial data are insufficient, but data collection is not an option, it is possible to supplement the data by exploiting the causal relations between the various variables that describe a disease process. We present a simple generic disease model with incidence, one prevalent state, and case fatality and remission. We derive a set of equations that describes this disease process and allows calculation of the complete epidemiology of a disease given a minimum of three input variables. We give the example of asthma with age-specific prevalence, remission, and mortality as inputs. Outputs are incidence and case fatality, among others. The set of equations is embedded in a software package called 'DisMod II', which is made available to the public domain by the World Health Organization

Estimating the prevalence of breast cancer using a disease model: data problems and trends

BACKGROUND: Health policy and planning depend on quantitative data of disease epidemiology. However, empirical data are often incomplete or are of questionable validity. Disease models describing the relationship between incidence, prevalence and mortality are used to detect data problems or supplement missing data. Because time trends in the data affect their outcome, we compared the extent to which trends and known data problems affected model outcome for breast cancer. METHODS: We calculated breast cancer prevalence from Dutch incidence and mortality data (the Netherlands Cancer Registry and Statistics Netherlands) and compared this to regionally available prevalence data (Eindhoven Cancer Registry, IKZ). Subsequently, we recalculated the model adjusting for 1) limitations of the prevalence data, 2) a trend in incidence, 3) secondary primaries, and 4) excess mortality due to non-breast cancer deaths. RESULTS: There was a large discrepancy between calculated and IKZ prevalence, which could be explained for 60% by the limitations of the prevalence data plus the trend in incidence. Secondary primaries and excess mortality had relatively small effects only (explaining 17% and 6%, respectively), leaving a smaller part of the difference unexplained. CONCLUSION: IPM models can be useful both for checking data inconsistencies and for supplementing incomplete data, but their results should be interpreted with caution. Unknown data problems and trends may affect the outcome and in the absence of additional data, expert opinion is the only available judge

Advances in the meta-analysis of heterogeneous clinical trials I: the inverse variance heterogeneity model

This article examines an improved alternative to the random effects (RE) model for meta-analysis of heterogeneous studies. It is shown that the known issues of underestimation of the statistical error and spuriously overconfident estimates with the RE model can be resolved by the use of an estimator under the fixed effect model assumption with a quasi-likelihood based variance structure — the IVhet model. Extensive simulations confirm that this estimator retains a correct coverage probability and a lower observed variance than the RE model estimator, regardless of heterogeneity. When the proposed IVhet method is applied to the controversial meta-analysis of intravenous magnesium for the prevention of mortality after myocardial infarction, the pooled OR is 1.01 (95% CI 0.71–1.46) which not only favors the larger studies but also indicates more uncertainty around the point estimate. In comparison, under the RE model the pooled OR is 0.71 (95% CI 0.57–0.89) which, given the simulation results, reflects underestimation of the statistical error. Given the compelling evidence generated, we recommend that the IVhet model replace both the FE and RE models. To facilitate this, it has been implemented into free meta-analysis software called MetaXL which can be downloaded from www.epigear.com

Contribution of trans-fatty acid intake to coronary heart disease burden in Australia: a modelling study

Trans-fatty acids (TFAs) intake has been consistently associated with a higher risk of coronary heart disease (CHD) mortality. We provided an updated assessment of TFA intake in Australian adults in 2010 and conducted modeling to estimate CHD mortality attributable to TFA intake. Data of the 2011–2012 National Nutrition and Physical Activity Survey was used to assess TFA intake. The CHD burden attributable to TFA was calculated by comparing the current level of TFA intake to a counterfactual setting where consumption was lowered to a theoretical minimum distribution of 0.5% energy. The average TFA intake among adults was 0.59% energy, and overall 10% of adults exceeded the World Health Organization (WHO) recommended limit of 1% energy. Education and income were moderately and inversely associated with TFA intake (p-value ≤ 0.001), with one in seven adults in the lowest income and education quintile having >1% energy from TFA. Australia had 487 CHD deaths (95% uncertainty interval, 367–615) due to TFA exposure, equivalent to 1.52% (95% uncertainty limits: 1.15%–1.92%) of all CHD mortality. The relative impact of TFA exposure on CHD mortality in Australia is limited, but, in absolute terms, still substantial. Policies aimed at reducing industrial TFA exposure can reduce socioeconomic inequalities in health and may therefore be desirable

The Burden of Trachoma in South Sudan: Assessing the Health Losses from a Condition of Graded Severity

Trachoma is an infectious disease that is endemic to the Republic of South Sudan. In the absence of appropriate treatment recurrent re-infection in an individual will lead to progressively severe states of trachoma, eventually leading to the loss of visual acuity and finally blindness. Here we distinguish between three separate states of disease: trachoma with normal vision, trachoma with low vision and trachoma with blindness. The first of these states, trachoma with normal vision, is the least severe and the impact of this state on a population has not been well investigated. Trachoma, even before any loss of vision, comes with a great deal of pain and social consequences, and thus disability. In this study we employ data from South Sudan and estimate the burden caused by trachoma with normal vision for the first time. In doing so, we also reveal the extent of the gaps in our knowledge surrounding the natural history of trachoma and highlight areas of research that require urgent attention

Extensional and Intensional Strategies

This paper is a contribution to the theoretical foundations of strategies. We first present a general definition of abstract strategies which is extensional in the sense that a strategy is defined explicitly as a set of derivations of an abstract reduction system. We then move to a more intensional definition supporting the abstract view but more operational in the sense that it describes a means for determining such a set. We characterize the class of extensional strategies that can be defined intensionally. We also give some hints towards a logical characterization of intensional strategies and propose a few challenging perspectives

The national burden of road traffic injuries in Thailand

Background: This study quantifies the burden of road traffic injuries (RTIs) in Thailand in 2004, incorporating new Thai data on mortality and the frequency and severity of long-term disability

EuroFlow Standardized Approach to Diagnostic Immunopheneotyping of Severe PID in Newborns and Young Children

The EuroFlow PID consortium developed a set of flow cytometry tests for evaluation of patients with suspicion of primary immunodeficiency (PID). In this technical report we evaluate the performance of the SCID-RTE tube that explores the presence of recent thymic emigrants (RTE) together with T-cell activation status and maturation stages and discuss its applicability in the context of the broader EuroFlow PID flow cytometry testing algorithm for diagnostic orientation of PID of the lymphoid system. We have analyzed peripheral blood cells of 26 patients diagnosed between birth and 2 years of age with a genetically defined primary immunodeficiency disorder: 1