New Anticoagulant Agents: Incidence of Adverse Drug Reactions and New Signals Thereof.

The aim of this study was to evaluate the adverse drug reaction (ADR) incidence rate and new signals thereof for classic compared with new anticoagulants in real-life ambulatory settings. The authors performed an observational cross-sectional study in two cohorts of surveyed patients treated with vitamin K antagonists (VKAs; acenocoumarol or warfarin) or nonvitamin K antagonist oral anticoagulants (NOACs; apixaban, edoxaban, rivaroxaban, dabigatran etexilate). Descriptive, clinical, and ADRs data were reported and analyzed through a bivariate analysis (odds ratio [OR]) to compare the ADRs incidence rate and an adaptation of Bayesian methodology (false discovery rate [FDR] < 0.05) to detect new signals. A total of 334 patients were surveyed-average international normalized ratio (INR) of 2.6-and 45.4% taking new anticoagulants. Note that 835 ADRs were reported; 2.5 per patient (2.8 in the VKA cohort, 2.1 in the NOAC cohort). The authors obtained higher risk of epistaxis (OR, 2.18; 95% confidence interval [CI], 1.01-4.74) and hematoma (OR, 2.43; 95% CI, 1.39-4.25) with VKAs and lower risk of global bleeding symptoms with NOACs (OR, 0.45; 95% CI, 0.28-0.71). After standardizing the data, a significant risk of diarrhea with VKAs was observed (OR, 3.37; 95% CI, 1.09-10.41). They also detected an intense positive signal regarding the use of VKAs and osteoporosis (FDR < 0.001), specifically acenocoumarol (FDR < 0.002). NOACs presented lower risk of bleeding, especially dabigatran (FDR < 0.031), and of dermatological pathologies with apixaban being the safest (FDR = 0.050). The lower risk of global bleeding and a potential protective effect against osteoporosis in patients treated with NOACs postulate them as safer than VKAs.

Transcriptional dissection of pancreatic tumors engrafted in mice.

BACKGROUND: Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient-derived xenograft (PDX) models is a promising platform for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine tumor environment on the gene expression of the engrafted human tumoral cells. METHODS: We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data of 18 PDX models, 53 primary tumors and 41 cell lines from PDAC. The results obtained in the PDAC system were further compared with public available microarray data from 42 PDX models, 108 primary tumors and 32 cell lines from hepatocellular carcinoma (HCC). We developed a robust analysis protocol to explore the gene expression space. In addition, we completed the analysis with a functional characterization of PDX models, including if changes were caused by murine environment or by serial passing. RESULTS: Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable from each other based on their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models can be separated into two different groups that share some partial similarity with their corresponding original primary tumors. Our results point to the lack of human stromal involvement in PDXs as a major factor contributing to their differences from the original primary tumors. The main functional differences between pancreatic PDX models and human PDAC are the lower expression of genes involved in pathways related to extracellular matrix and hemostasis and the up- regulation of cell cycle genes. Importantly, most of these differences are detected in the first passages after the tumor engraftment. CONCLUSIONS: Our results suggest that PDX models of PDAC and HCC retain, to some extent, a gene expression memory of the original primary tumors, while this pattern is not detected in conventional cancer cell lines. Expression changes in PDXs are mainly related to pathways reflecting the lack of human infiltrating cells and the adaptation to a new environment. We also provide evidence of the stability of gene expression patterns over subsequent passages, indicating early phases of the adaptation process.

Physical activity, quality of life and symptoms of depression in community-dwelling and institutionalized older adults.

This study was aimed to investigate in a sample of Spanish elderly whether measures of physical activity are related to health-related quality of life (HRQoL) and symptoms of depression in community dwelling and institutionalized elderly. The sample was a cohort of 436 elderly (234 women and 202 men, aged 60-98 years) from the North of Spain. 58% were community-dwellers and 42% were institutionalized in senior residences. Participants completed measures of physical activity (Yale Physical Activity Survey, YPAS), HRQoL (Medical Outcomes Study 36-item Short Form Health Survey, SF-36) and symptoms of depression (Geriatric Depression Scale, GDS). All SF-36 domains, except role-emotional, were significantly correlated with the YPAS activity dimension summary index. Physical function, role-physical, general health and vitality correlated with total time activity, and correlations were observed between weekly energy expenditure and physical function, role physical, vitality and mental health. Depressive symptom scores correlated significantly with the YPAS activity dimension summary index and the weekly energy expenditure. Scores for various domains of the SF-36 and for depressive symptoms significantly differed among less and more active individuals of the same sex and institutionalization category. Differences generally reached a higher extent in institutionalized subjects in comparison to community dwellers. In conclusion, physical activity was related to different domains of both the physical and mental components of HRQoL and to decreased depressive symptoms. Results emphasize the positive effects of physical activity in both community-dwelling and institutionalized older adults.

Feelings of well being in elderly people: relationship to physical activity and physical function.

The aim of the research was to investigate in a sample of Spanish elderly whether measures of physical activity and physical function are related to feelings of well being, and whether level of dependence is a moderator in the relation of well being, physical activity and physical function. The sample was a cohort of 151 elderly people (89 women and 62 men, aged 60-98 years) from the North of Spain. Participants completed surveys including demographic characteristics, and measures of physical activity (Yale Physical Activity Survey, YPAS), instrumental activities of daily living (Barthel Index, BI) and well being (Psychological Well Being Scale, from Spanish: Escala de Bienestar Psicológico=EBP). Components of the physical function were measured by the Senior Fitness Test (SFT). Upper and lower body strength, dynamic balance, aerobic endurance, self-reported weekly energy expenditure and physical activity total time were significantly correlated with both Material and Subjective well being. All components of physical function were significantly impaired in dependent subjects when compared to independent individuals of the same sex and physical activity category. Significant differences were also observed in Subjective well being among less active dependent or independent individuals. In conclusion, physical function and physical activity are related to feelings of well being, and results emphasize the positive functional and psychological effects of physical activity in dependent subjects.