BackgroundThe EORTC QLU-C10D is a new multi-attribute utility instrument derived from the widely used cancer-specific quality-of-life (QOL) questionnaire, EORTC QLQ-C30. The QLU-C10D contains ten dimensions (Physical, Role, Social and Emotional Functioning; Pain, Fatigue, Sleep, Appetite, Nausea, Bowel Problems), each with four levels. To be used in cost-utility analysis, country-specific valuation sets are required.ObjectiveThe aim of this study was to provide Australian utility weights for the QLU-C10D.MethodsAn Australian online panel was quota-sampled to ensure population representativeness by sex and age (≥ 18 years). Participants completed a discrete choice experiment (DCE) consisting of 16 choice-pairs. Each pair comprised two QLU-C10D health states plus life expectancy. Data were analysed using conditional logistic regression, parameterised to fit the quality-adjusted life-year framework. Utility weights were calculated as the ratio of each QOL dimension-level coefficient to the coefficient on life expectancy.ResultsA total of 1979 panel members opted in, 1904 (96%) completed at least one choice-pair, and 1846 (93%) completed all 16 choice-pairs. Dimension weights were generally monotonic: poorer levels within each dimension were generally associated with greater utility decrements. The dimensions that impacted most on choice were, in order, Physical Functioning, Pain, Role Functioning and Emotional Functioning. Oncology-relevant dimensions with moderate impact were Nausea and Bowel Problems. Fatigue, Trouble Sleeping and Appetite had relatively small impact. The value of the worst health state was -0.096, somewhat worse than death.ConclusionsThis study provides the first country-specific value set for the QLU-C10D, which can facilitate cost-utility analyses when applied to data collected with the EORTC QLQ-C30, prospectively and retrospectively.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-017-0582-5) contains supplementary material, which is available to authorized users.

Abstract:Purpose: To derive a health state classification system (HSCS) from the cancerspecific quality of life questionnaire, the EORTC QLQ-C30, as the basis for a multiattribute utility instrument.Methods: The conceptual model for the HSCS was based on the established domain structure of the QLQ-C30. Several criteria were considered to select a subset of dimensions and items for the HSCS. Expert opinion and patient input informed a priori Powered by Edit orial Manager® and ProduXion Manager® from Aries Syst em s Corporat ionselection of key dimensions. Psychometric criteria were assessed via secondary analysis of a pooled dataset comprising HRQOL and clinical data from 2616 patients from eight countries and a range of primary cancer sites, disease stages, and treatments. We used confirmatory factor analysis (CFA) to assess the conceptual model's robustness and generalisability. We assessed item floor effects (>75% observations at lowest score), disordered item response thresholds, coverage of the latent variable and differential item function (DIF) using Rasch analysis. We calculated effect sizes for known group comparisons based on disease stage and responsiveness to change. Seventy-nine cancer patients assessed the relative importance of items within dimensions.Results: CFA supported the conceptual model and its generalizability across primary cancer sites. After considering all criteria, 12 items were selected representing 10 dimensions: physical functioning (mobility), role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems.

Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.

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This study demonstrates that chronic ethanol-induced alterations in the glutathione/GSHPx-1 antioxidant system might promote oxidative modification of liver proteins, namely those of the mitochondrion, which could contribute to the adverse effects of ethanol on the liver.