The relationship between EQ-5D, HAQ and pain in patients with rheumatoid arthritis: further validation and development of the limited dependent variable, mixture model approach

Objective To provide robust estimates of EQ-5D as a function of the Health Assessment Questionnaire (HAQ) and pain in patients with rheumatoid arthritis. Method Repeated observations of patients diagnosed with RA in a US observational cohort (n=100,398 observations) who provided data on HAQ, pain on a visual analogue scale and the EQ-5D questionnaire. We use a bespoke mixture modelling approach to appropriately reflect the characteristics of the EQ-5D instrument and compare this to results from linear regression. Results The addition of pain alongside HAQ as an explanatory variable substantially improves explanatory power. The preferred model is a four component mixture. Unlike the linear regression it exhibits very good fit to the data, does not suffer from problems of bias or predict values outside the feasible range. Conclusions It is appropriate to model the relationship between HAQ and EQ-5D but only if suitable statistical methods are applied. Linear models underestimate the QALY benefits, and therefore the cost effectiveness, of therapies. The bespoke mixture model approach outlined here overcomes this problem. The addition of pain as an explanatory variable greatly improves the estimates

Scandium: A key element for understanding Am stars

{\rm Context.} Atomic diffusion is believed to cause the abundance anomalies observed in AmFm stars. However, the detailed process has still not been well-established. For instance, two possible scenarios for the diffusion theory are presently envisaged. They differ mainly by the depth from which the abundance anomalies emanate. The first scenario predicts that the abundances are modified in the superficial regions of the star, just below the hydrogen convection zone. The second scenario predicts that a much deeper extension of the mixing zone exists due to the convection caused by Fe accumulation in regions below the hydrogen convection zone. {\rm Aims.} We calculate much more accurate radiative accelerations of Sc than previously, to better understand the observed abundance anomalies of this element. We believe that it is a key element to use as a diagnostic tool for understanding AmFm stars. {\rmMethods.} The method employed to obtain these radiative accelerations is based on an interpolation from the parameters of the so-called SVP parametric method. {\rm Results.} The radiative accelerations, shown here in a typical Am stellar model, are discussed in light of the observed anomalies of Ca and Sc. Our results suggest that the deeper mixing scenario is not entirely satisfactory: the mixing zone should be deeper than what is predicted by recent models to account for observed Sc underabundances. Our results seem more compatible with the scenario where the abundances anomalies are created in the superficial regions. However, only detailed evolutionary modelling with mass loss and diffusion of all important species, including Ca and Sc, with accurate radiative accelerations, will be able to give more insight into where the source of these anomalies occur in AmFm stars.Comment: 6 pages, 3 figures, accepted for publication in A&

A comparison of direct and indirect methods for the estimation of health utilities from clinical outcomes

Background: Analysts often need to estimate health state utility values as a function of other outcome measures. Utility values like EQ-5D have several unusual characteristics that make standard statistical methods inappropriate. We have developed a bespoke approach based on mixture models to directly estimate EQ-5D. An indirect method, “response mapping”, first estimates the level on each of the five dimensions of the EQ-5D descriptive system and then calculates the expected tariff score. These methods have never previously been compared. Methods: We use a large observational database of patients diagnosed with Rheumatoid Arthritis (n=100,398 observations). Direct estimation of UK EQ-5D scores as a function of Health Assessment Questionnaire (HAQ), pain and age was performed using a limited dependent variable mixture model. Indirect modelling was undertaken using a set of generalized ordered probit models with expected tariff scores calculated mathematically. Linear regression was reported for comparison purposes. Results: The linear model fits poorly, particularly at the extremes of the distribution. Both the bespoke mixture model and the generalized ordered probit approach offer improvements in fit over the entire range of EQ-5D. Mean average error is 10% and 5% lower compared to the linear model respectively. Root mean squared error is 3% and 2% lower. The mixture model demonstrates superior performance to the indirect method across almost the entire range of pain and HAQ. Limitations: There is limited data from patients in the most extreme HAQ health states. Conclusions: Modelling of EQ-5D from clinical measures is best performed directly using the bespoke mixture model. This substantially outperforms the indirect method in this example. Linear models are inappropriate, suffer from systematic bias and generate values outside the feasible range

Evaluating kernels on Xeon Phi to accelerate Gysela application

This work describes the challenges presented by porting parts ofthe Gysela code to the Intel Xeon Phi coprocessor, as well as techniques used for optimization, vectorization and tuning that can be applied to other applications. We evaluate the performance of somegeneric micro-benchmark on Phi versus Intel Sandy Bridge. Several interpolation kernels useful for the Gysela application are analyzed and the performance are shown. Some memory-bound and compute-bound kernels are accelerated by a factor 2 on the Phi device compared to Sandy architecture. Nevertheless, it is hard, if not impossible, to reach a large fraction of the peek performance on the Phi device,especially for real-life applications as Gysela. A collateral benefit of this optimization and tuning work is that the execution time of Gysela (using 4D advections) has decreased on a standard architecture such as Intel Sandy Bridge.Comment: submitted to ESAIM proceedings for CEMRACS 2014 summer school version reviewe

Sudden cardiac death in the young (5-39 years) in the canton of Vaud, Switzerland.

Sudden cardiac death (SCD) among the young is a rare and devastating event, but its exact incidence in many countries remains unknown. An autopsy is recommended in every case because some of the cardiac pathologies may have a genetic origin, which can have an impact on the living family members. The aims of this retrospective study completed in the canton of Vaud, Switzerland were to determine both the incidence of SCD and the autopsy rate for individuals from 5 to 39 years of age. The study was conducted from 2000 to 2007 on the basis of official statistics and analysis of the International Classification of Diseases codes for potential SCDs and other deaths that might have been due to cardiac disease. During the 8 year study period there was an average of 292'546 persons aged 5-39 and there were a total of 1122 deaths, certified as potential SCDs in 3.6% of cases. The calculated incidence is 1.71/100'000 person-years (2.73 for men and 0.69 for women). If all possible cases of SCD (unexplained deaths, drowning, traffic accidents, etc.) are included, the incidence increases to 13.67/100'000 person-years. However, the quality of the officially available data was insufficient to provide an accurate incidence of SCD as well as autopsy rates. The presumed autopsy rate of sudden deaths classified as diseases of the circulatory system is 47.5%. For deaths of unknown cause (11.1% of the deaths), the autopsy was conducted in 13.7% of the cases according to codified data. The incidence of presumed SCD in the canton of Vaud, Switzerland, is comparable to the data published in the literature for other geographic regions but may be underestimated as it does not take into account other potential SCDs, as unexplained deaths. Increasing the autopsy rate of SCD in the young, better management of information obtained from autopsies as well developing of structured registry could improve the reliability of the statistical data, optimize the diagnostic procedures, and the preventive measures for the family members