Vorapaxar in the secondary prevention of atherothrombotic events.

BACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.).

Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival.

The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tumors. We found that Fn14, when expressed in tumors, causes cachexia and that antibodies against Fn14 dramatically extended lifespan by inhibiting tumor-induced weight loss although having only moderate inhibitory effects on tumor growth. Anti-Fn14 antibodies prevented tumor-induced inflammation and loss of fat and muscle mass. Fn14 signaling in the tumor, rather than host, is responsible for inducing this cachexia because tumors in Fn14- and TWEAK-deficient hosts developed cachexia that was comparable to that of wild-type mice. These results extend the role of Fn14 in wound repair and muscle development to involvement in the etiology of cachexia and indicate that Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients.

Transcriptional regulator PRDM12 is essential for human pain perception.

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics.

The Feminization of Occupations and Change in Wages : a Panel Analysis of Britain, Germany, and Switzerland

In the past four decades, women have made major inroads into occupations previously dominated by men. This paper examines whether occupational feminization is accompanied by a decline in wages: Do workers suffer a wage penalty if they remain in, or move into, feminizing occupations? We analyze this question over the 1990s and 2000s in Britain, Germany, and Switzerland, using longitudinal panel data to estimate individual fixed effects for men and women. Moving from an entirely male to an entirely female occupation entails a loss in individual earnings of 13 percent in Britain, 7 percent in Switzerland, and 3 percent in Germany. The impact of occupational feminization on wages is not linear, but sets apart occupations holding more than 60 percent of women. Moving into such female occupations incurs a wage penalty. Contrary to the prevailing idea in economics, differences in productivity-human capital, job-specific skills, and time investment-do not fully explain the wage gap between male and female occupations. The wage penalty associated with working in a female occupation is also much larger where employer discretion is greater-in the private sector-than where wagesetting is guided by formal rules-the public sector. These findings suggest that wage disparities across male and female occupations are due to gender devaluation.

Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial.

BACKGROUND: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. METHODS: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. RESULTS: Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. CONCLUSIONS: Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

Reliability and validity of nonverbal thin slices in social interactions

Four studies investigated the reliability and validity of thin slices of nonverbal behavior from social interactions including (1) how well individual slices of a given behavior predict other slices in the same interaction; (2) how well a slice of a given behavior represents the entirety of that behavior within an interaction; (3) how long a slice is necessary to sufficiently represent the entirety of a behavior within an interaction; (4) which slices best capture the entirety of behavior, across different behaviors; and (5) which behaviors (of six measured behaviors) are best captured by slices. Notable findings included strong reliability and validity for thin slices of gaze and nods, and that a 1.5 min slice from the start of an interaction may adequately represent some behaviors. Results provide useful information to researchers making decisions about slice measurement of behavior.

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The paper engages the question of how traditional religion persist in an increasingly problematic and complex swiss context. In particular, the chapter looks at the phenomenon of charismatic worship as a vehicle for resignifying the meaning of chronic suffering, over and against the traditional evangelical expectation that worldly hardship is but a temporary trial, to be endured and overcome by true believers. The experience of ongoing physical and psychological suffering is mediated by ritualized narratives, which resituate the afflicted "stakeholders" as important models of Christian life. In so doing, these narratives richly dramatize the resolution of theodicy by showing that, far from being absent in the lives of sufferers, God is especially present.

A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study.

BACKGROUND: Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. METHODS: The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. RESULTS: There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. CONCLUSION: Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

Le bien-être spirituel des personnes nouvellement diagnostiquees d'un cancer en début de traitement : étude descriptive correlationnelle

Problématique. Le cancer touche beaucoup de personnes en Suisse et un grand nombre en décèdent encore. Recevoir une telle annonce plonge le malade dans une crise spirituelle qui bouleverse complètement sa vie. L'incertitude de son avenir, la sensibilisation à sa finitude sont exacerbées par la proximité de la mort et par les symptômes du cancer: combien de temps les malades vont-ils encore vivre ? Qu'adviendra-t-il de leur corps désormais confronté aux symptômes du cancer et à ses traitements? Les professionnels de la santé s'attacheraient davantage au bien-être spirituel des personnes en phase palliative et peu d'études se sont intéressées au bien-être spirituel des personnes en début de traitement au moment d'une telle nouvelle. But. Décrire le bien-être spirituel des personnes nouvellement diagnostiquées d'un cancer en début de traitement, explorer sa relation avec les symptômes du cancer et l'interdépendance des différentes variables. Méthode. Cette recherche descriptive corrélationnelle a été conduite auprès de 30 patients recrutés selon un échantillonnage de convenance dans un centre d'oncologie ambulatoire situé dans un hôpital universitaire suisse. Les données ont été recueillies au moyen d'un formulaire de données sociodémographiques et de santé ainsi que de deux instruments de mesure: ESAS (Edmonton Symptom Assessment System) (Bruera, Kuehn, Miller, Selmser, & Macmillan, 1991) et FACIT-Sp-12 (Functional Assessment of Chronic Ilness Therapy-Spiritual Well- Being) (Canada, Murphy, Fitchett, Peterman, & Schover, 2008). Le premier a permis de mesurer les symptômes du cancer et le second, le bien-être spirituel. Les données ont été traitées par des analyses descriptives et corrélationnelles avec le logiciel STATA Version 11. Résultats. Les répondants étaient représentés en majorité par des femmes (73%) atteintes d'un cancer du sein (60%). La plupart des participants étaient croyants (97%) de confession catholique (50%), protestante (47%) ou musulmane (3%). Sur un rang de 0 à 48, la plupart des participants ont présenté un niveau de bien-être spirituel élevé (M=36,5 ; ĒT=6,6). Les dimensions de ce dernier atteignaient également de très bon scores : sur un rang de 0 à 16, la dimension sens affichait la moyenne la plus élevée (M=14,2 ; ĒT=1,9), suivie de celle de paix (M=12,1 ; ĒT=2,7) et finalement de celle de foi (M=10,2 ; ĒT=3,2). Le bien-être spirituel était lié significativement à l'âge (p= 0,04), à la dépression (p= 0,01) et au mal-être (p= 0,02) : être jeune, présenter des symptomatologies dépressives et de mal-être influencent négativement le bien-être spirituel des malades. Conclusions. Dépister précocement la dépression et le mal-être des personnes qui surgissent souvent à la révélation du cancer est important. Il faut se soucier particulièrement du bien-être spirituel des personnes âgées et les accompagner dans leur quête de sens singulière par la prière, l'abnégation, le récit de vie, les relations avec l'entourage, l'introspection, pour adoucir l'incertitude de l'avenir et la mouvance identitaire qui composent désormais leur quotidien.