Discriminant validity, responsiveness and reliability of the rheumatoid arthritis-specific Work Productivity Survey (WPS-RA)

INTRODUCTION: The rheumatoid arthritis-specific Work Productivity Survey (WPS-RA) measures the impact of rheumatoid arthritis (RA) and treatment on patient productivity within and outside the home. It contains nine questions addressing employment status, productivity within and outside the home, and daily activities. The objective of this paper was to evaluate the discriminant validity, responsiveness, and reliability of the WPS-RA in patients with active RA. METHODS: Two hundred twenty subjects (mean age was 53.8 years, 83.6% were female, mean disease duration was 9.54 years, mean number of disease-modifying anti-rheumatic drugs failed was 2, and 38.6% were employed outside the home) in a phase III, 24-week, double-blind, placebo-controlled trial completed the WPS-RA at baseline and every 4 weeks until withdrawal/study completion. Validity was evaluated via known groups using baseline data (first and third quartiles of subjects' Health Assessment Questionnaire – Disability Index [HAQ-DI] scores and Short Form-36 health survey [SF-36] scores). To evaluate responsiveness, mean changes in WPS-RA at week 24 were compared between American College of Rheumatology 20% improvement criteria (ACR20) (or HAQ-DI) responders and non-responders. Standardized response mean (SRM) was also used to quantify responsiveness. All group comparisons were conducted using a non-parametric bootstrap-t method. RESULTS: Subjects with lower HAQ-DI or SF-36 scores generally had statistically greater RA-associated losses in productivity within and outside the home compared with subjects with higher scores (25 of 32 evaluations were statistically significant). Smallest differences between groupswere seen in work absenteeism and days with outside help. At week 24, ACR20 and HAQ-DI responders reported large improvements in productivity within and outside the home; non-responders reported mainly a worsening in productivity (P ≤ 0.05). Effect size for productivity changes in ACR20 or HAQ-DI responders was moderate to large for six out of eight items (SRM = 0.48 to 1.12). The effect size was small for work absenteeism and days with outside help. (SRM = 0.4 and 0.24, respectively). In non-responders, the magnitude of change was negligible (SRM < 0.1) or small (SRM < 0.3). CONCLUSIONS: The WPS-RA has demonstrated properties of discriminative validity, reliability, and responsiveness for the measurement of productivity within and outside the home in subjects with active RA

Current Trends in Glioblastoma Treatment

Glioblastoma (also called glioblastoma multiforme – GBM) is a primary brain neoplasm, representing about 55% of all gliomas. It is a very aggressive and infiltrative tumor. Glioblastoma is usually highly malignant, with more than 90% 5-year mortality and a median survival of about 14.6 months. Compared to other cancers, the survival rate has not greatly changed over time and no current treatment is curative for this disease. Because the tumor has a heterogeneous cell population containing several types of cells, the treatment for GBM is one of the most challenging in clinical oncology. This chapter will discuss the current approaches in glioblastoma treatment, including resection techniques, chemotherapy and radiation therapy

Biobanking in a Constantly Developing Medical World

Biobank is a very sophisticated system that consists of a programmed storage of biological material and corresponding data. Biobanks are created to be used in medical research, in clinical and translational medicine, and in healthcare. In the past 20 years, a large number of biobanks have been set up around the world, to support the modern research directions in medicine such as omix and personalized medicine. More recently, embryonic and adult stem cell banks have been developed. Stem cell banking was reported to be required for medical research as well as clinical transplant applications. The quality of the samples stored in a biobank is very important. The standardization is also important; the biological material stored in a biobank must be processed in a manner that allows compatibility with other biobanks that preserve samples in the same field. In this paper, we review some issues related to biobanks purposes, quality, harmonization, and their financial and ethical aspects

Original Article Targeting the VEGF and PDGF signaling pathway in glioblastoma treatment

Abstract: Growth factor receptors dysfunction has previously been correlated with glioma cell proliferation, ability to evade apoptosis, neo-angiogenesis and resistance to therapy. Antineoplastic molecules targeting growth factor receptors are in clinical handling, however the efficacy of these compounds has often been limited by the signaling redundancy. Here, we analyzed the effect of AG1433 (a PDGFR inhibitor), SU1498 (a VEGFR inhibitor) and BEZ235 (a PI3K/Akt/mTOR signaling pathways inhibitor) on glioblastoma cells in vitro. For this study, we used a low passage glioblastoma cell line (GB9B). Assessment of cell number over 72 h showed that the growth rate was 0.3024 and the doubling time of GB9B was 2.29 days. Similar cytotoxic effects were observed by using AG1433 and SU1498 treatment, while dual PI3K/Akt/mTOR inhibition by BEZ235 was more efficient in killing glioblastoma cells than individual PDGFR or VEGFR targeting. In SU1498 treated cells, caspase 3 activity was detected 3 hours after the treatment, while activation of caspase 8 and 9 was detected 48 hours later. AG1433 treatment induced caspase 3, 8 and 9, 3 hours after the treatment. BEZ235 treatment resulted in early caspase 3 and 8 activation, 3 hours after the treatment and an activation of caspase 9, 8 hours later

Modelling dependence in actuarial science, with emphasis on credibility theory and copulas

One basic problem in statistical sciences is to understand the relationships among multivariate outcomes. Although it remains an important tool and is widely applicable, the regression analysis is limited by the basic setup that requires to identify one dimension of the outcomes as the primary measure of interest (the "dependent" variable) and other dimensions as supporting this variable (the "explanatory" variables). There are situations where this relationship is not of primary interest. For example, in actuarial sciences, one might be interested to see the dependence between annual claim numbers of a policyholder and its impact on the premium or the dependence between the claim amounts and the expenses related to them. In such cases the normality hypothesis fails, thus Pearson's correlation or concepts based on linearity are no longer the best ones to be used. Therefore, in order to quantify the dependence between non-normal outcomes one needs different statistical tools, such as, for example, the dependence concepts and the copulas. This thesis is devoted to modelling dependence with applications in actuarial sciences and is divided in two parts: the first one concerns dependence in frequency credibility models and the second one dependence between continuous outcomes. In each part of the thesis we resort to different tools, the stochastic orderings (which arise from the dependence concepts), and copulas, respectively. During the last decade of the 20th century, the world of insurance was confronted with important developments of the a posteriori tarification, especially in the field of credibility. This was dued to the easing of insurance markets in the European Union, which gave rise to an advanced segmentation. The first important contribution is due to Dionne & Vanasse (1989), who proposed a credibility model which integrates a priori and a posteriori information on an individual basis. These authors introduced a regression component in the Poisson counting model in order to use all available information in the estimation of accident frequency. The unexplained heterogeneity was then modeled by the introduction of a latent variable representing the influence of hidden policy characteristics. The vast majority of the papers appeared in the actuarial literature considered time-independent (or static) heterogeneous models. Noticeable exceptions include the pioneering papers by Gerber & Jones (1975), Sundt (1988) and Pinquet, Guillén & Bolancé (2001, 2003). The allowance for an unknown underlying random parameter that develops over time is justified since unobservable factors influencing the driving abilities are not constant. One might consider either shocks (induced by events like divorces or nervous breakdown, for instance) or continuous modifications (e.g. due to learning effect). In the first part we study the recently introduced models in the frequency credibility theory, which can be seen as models of time series for count data, adapted to actuarial problems. More precisely we will examine the kind of dependence induced among annual claim numbers by the introduction of random effects taking unexplained heterogeneity, when these random effects are static and time-dependent. We will also make precise the effect of reporting claims on the a posteriori distribution of the random effect. This will be done by establishing some stochastic monotonicity property of the a posteriori distribution with respect to the claims history.[...](STAT 3)--UCL, 200

On the stochastic increasingness of future claims in the Bühlmann linear credibility premium

Since Nelder & Verrall (1997), the connection between Generalized Linear Mod- els (GLM’s) and credibility theory has been recognized in actuarial science. Specifically, the credibility construction amounts to add a random effect on the same scale as the fixed effects to model unexplained heterogeneity. The present paper aims to examine the dependence ex- isting between future claims (severity or frequency components) and the Bu ̈hlmann linear credibility premium. As expected, future claims are shown to increase with the amount of Bu ̈hlmann premium

On the dependence induced by frequency credibility models - 2 : Dynamic random effects

In an effort to incorporate the date of claims in risk prediction, Pinquet, Guill ́en & Bolanc ́e (2001) specified a stationary process for the random effects. This paper aims to investigate the type of dependence induced by such a dynamic heterogeneity. Contrarily to the static case studied in Purcaru & Denuit (2001), the correlation structure between latent variables now crucially affects the association between claim numbers. In particular, taking comonotonic random effects gives the static credibility model considered by these authors, whereas taking different copulas yields various dependence structures

On the dependence induced by frequency credibility models - 1 : Time-invariant random effects

In casualty insurance, actuaries usually resort to random effects to take unexplained heterogeneity into account in the spirit of the Bu ̈hlmann-Straub model. This paper aims to study the kind of dependence induced by the introduction of common latent variables in the annual numbers of claims reported by policyholders. It will be seen that this classical construction entails strong positive dependence between the underlying random variables