Cerebrospinal fluid biomarker candidates associated with human WNV neuroinvasive disease

During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF) cases, but also of West Nile neuroinvasive disease (WNND). The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS) structures, modifications in the cerebrospinal fluid (CSF) composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1), a protein reported with anti-viral effects, presente

Pharmacokinetics and exposure-effect relationships of capecitabine in elderly patients with breast or colorectal cancer.: Population pharmacokinetics of capecitabine in elderly

International audiencePURPOSE: The aims of the present study were (1) to investigate the impact of great age on pharmacokinetics of capecitabine and its metabolites and (2) to evaluate the exposure-effect relationship of capecitabine in elderly patients. METHODS: Data collected from 20 elderly patients (75-92 years old) with breast or colorectal cancer who received oral capecitabine were analyzed. In order to study the old age effect on pharmacokinetics, data collected from two phase I studies involving 40 younger adults (<75 years old) with metastatic cancer who received oral capecitabine were added in the database. The population pharmacokinetic analysis was based on a four-compartment model describing the sequence of capecitabine and three of its metabolites. RESULTS: The absorption rate constant was found lower in the oldest patient group (≥75 years) compared with the youngest group, and the constant rate elimination of the 5-fluorouracil metabolite was found decreased over time (i.e., after 2 consecutive weeks of capecitabine administration). This time effect was not found different between the two age groups. In elderly patients, the exposure-safety analysis showed, from the second cycle of chemotherapy, significantly higher median exposures of capecitabine and its metabolites (5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine and 5-fluorouracil) in patients who experienced hand-foot syndrome compared with patients who did not. CONCLUSION: This study puts forward new arguments for the treatment of elderly cancer patients who could benefit from capecitabine chemotherapy with acceptable toxicity

Joint models for longitudinal and time-to-event data: a review of reporting quality with a view to meta-analysis

Background Joint models for longitudinal and time-to-event data are commonly used to simultaneously analyse correlated data in single study cases. Synthesis of evidence from multiple studies using meta-analysis is a natural next step but its feasibility depends heavily on the standard of reporting of joint models in the medical literature. During this review we aim to assess the current standard of reporting of joint models applied in the literature, and to determine whether current reporting standards would allow or hinder future aggregate data meta-analyses of model results. Methods We undertook a literature review of non-methodological studies that involved joint modelling of longitudinal and time-to-event medical data. Study characteristics were extracted and an assessment of whether separate meta-analyses for longitudinal, time-to-event and association parameters were possible was made. Results The 65 studies identified used a wide range of joint modelling methods in a selection of software. Identified studies concerned a variety of disease areas. The majority of studies reported adequate information to conduct a meta-analysis (67.7% for longitudinal parameter aggregate data meta-analysis, 69.2% for time-to-event parameter aggregate data meta-analysis, 76.9% for association parameter aggregate data meta-analysis). In some cases model structure was difficult to ascertain from the published reports. Conclusions Whilst extraction of sufficient information to permit meta-analyses was possible in a majority of cases, the standard of reporting of joint models should be maintained and improved. Recommendations for future practice include clear statement of model structure, of values of estimated parameters, of software used and of statistical methods applied