Health-related quality of life in Denmark on a relative scale:mini-catalogue of mean EQ-5D-3L index scores for 17 common chronic conditions

In health economic evaluations the quality-adjusted life-year (QALY) is one of the preferred outcome measures. Catalogues of median-based decrements in EQ-5D-3L index scores for chronic conditions exist to inform economic evaluations but may not be appropriate for this purpose as mean, rather than median, EQ-5D-3L index scores are of primary interest. Firstly, we aim to estimate mean decrements in EQ-5D-3L index scores through a simple stratified analysis as an alternative to regression modelling. In addition, we aim to estimate the mean decrement in EQ-5D-3L index scores in percent relative to a disease-free reference population. Secondly, we aim to handle both multiple imputation and appropriate estimation of standard errors in the presence of individual sampling weights. Data on EQ-5D-3L from the National Health Profile, Denmark, 2013, were used to estimate the EQ-5D-3L index scores. Calculation of decrements in EQ-5D-3L index scores of chronic conditions was done while controlling for the additional number of chronic conditions beside the one in question, age and sex. Also, a test of homogeneity of decrements across subgroups was conducted. We provide a mini-catalogue of new percentage-scale decrements in EQ-5D-3L index scores. For example, we estimated that angina was associated with an 8.2% reduction in the EQ-5D-3L index score compared to a reference group without angina. If the mean EQ-5D-3L score was 0.848 among corresponding groups without angina; angina patients would have an EQ-5D-3L index score of (1-0.082)·0.848=0.778 using the percentage-scale. The estimated percentage reduction in the EQ-5D-3L index score was homogenous regardless of the number of additional chronic conditions, age and sex. We suggest a percentage-scale estimation of EQ-5D-3L index scores for chronic disorders as an alternative to existing median-based methods. Our estimates stem from a simpler model, which, we argue, is easier to use and interpret.Published: Online May 2016. In print August 2016

Asynchronous Probabilistic Couplings in Higher-Order Separation Logic

Probabilistic couplings are the foundation for many probabilistic relational program logics and arise when relating random sampling statements across two programs. In relational program logics, this manifests as dedicated coupling rules that, e.g., say we may reason as if two sampling statements return the same value. However, this approach fundamentally requires aligning or "synchronizing" the sampling statements of the two programs which is not always possible. In this paper, we develop Clutch, a higher-order probabilistic relational separation logic that addresses this issue by supporting asynchronous probabilistic couplings. We use Clutch to develop a logical step-indexed logical relational to reason about contextual refinement and equivalence of higher-order programs written in a rich language with higher-order local state and impredicative polymorphism. Finally, we demonstrate the usefulness of our approach on a number of case studies. All the results that appear in the paper have been formalized in the Coq proof assistant using the Coquelicot library and the Iris separation logic framework

¹⁸F-FDG PET/CT-based early treatment response evaluation of nanoparticle-assisted photothermal cancer therapy

Within the field of nanoparticle-assisted photothermal cancer therapy, focus has mostly been on developing novel heat-generating nanoparticles with the right optical and dimensional properties. Comparison and evaluation of their performance in tumor-bearing animals are commonly assessed by changes in tumor volume; however, this is usually a late-occurring event. This study implements 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging to perform early evaluation of the treatment outcome of photothermal therapy. Silica-gold nanoshells (NS) are administered intravenously to nude mice bearing human neuroendocrine tumor xenografts and the tumors are irradiated by a near-infrared laser. The animals are positron emission tomography scanned with 2-deoxy-2-[F-18]fluoro-D-glucose one day before and one day after treatment. Using this setup, a significant decrease in tumor uptake of 2-deoxy-2-[F-18]fluoro-D-glucose is found already one day after therapy in the group receiving NS and laser treatment compared to control animals. At this time point no change in tumor volume can be detected. Moreover, the change in tumor uptake, is used to stratify the animals into responders and non-responders, where the responding group matched improved survival. Overall, these findings support the use of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging for preclinical and clinical evaluation and optimization of photothermal therapy

Adjustment of foreign EQ-5D-3L utilities can increase their transferability

BACKGROUND: Foreign utilities of the EQ-5D-3L (3-level version of the EuroQol-5 Dimension of health questionnaire) are not readily transferrable to economic evaluations conducted from a national perspective. It has been advised to avoid transferring mean utilities from one country to another without adjusting them; yet no such method exists. PURPOSE: The present study aimed to develop a method for adjusting mean utilities to increase their transferability from one country to another. METHODS: Seven datasets containing EQ-5D-3L answers were valued using value sets from four countries: the UK, the Netherlands, Germany, and Spain. Hereby, seven mean utility values were obtained for each country. This allowed for three pairwise comparisons: 1) UK mean values vs Dutch mean values; 2) UK mean values vs German mean values; and 3) UK mean values vs Spanish mean values. For each of these three comparisons, a regression model was fitted using the mean UK utilities as the dependent variable and the other country’s mean utilities as the independent variable. The coefficients from the three regression models were validated using results from a published article containing mean utilities obtained by valuing the EQ-5D-3L data using all four value sets. RESULTS: The findings suggested that adjustment of foreign utilities may increase transferability between countries where value sets are not comparable. It was possible to adjust the mean utilities valued by the Dutch and German value sets to make them reflect mean UK utilities as there were substantial differences between these value sets. Transferability of the Spanish mean utility values was not improved as the Spanish and UK value sets are sufficiently similar. CONCLUSION: It is feasible to adjust foreign mean utilities of the EQ-5D-3L to make them reflect national preferences for health