Telaprevir- and boceprevir-based tritherapies in real practice for F3-F4 pretreated hepatitis C virus patients

AIM:To assess,in a routine practice setting,the sus-tained virologic response(SVR) to telaprevir(TPV) or boceprevir(BOC) in hepatitis C virus(HCV) nullresponders or relapsers with severe liver fibrosis.METHODS:One hundred twenty-five patients were treated prospectively for 48 wk with TPV or BOC + pegylated-interferon(peg-INF) α2a + ribavirin(PR) according to standard treatment schedules without randomization.These patients were treated in routine practice settings in 10 public or private health care centers,and the data were prospectively collected.Only patients with severe liver fibrosis(Metavir scores of F3 or F4 upon liver biopsy or liver stiffness assessed by elastography),genotype 1 HCV and who were null-responders or relapsers to prior PR combination therapy were included in this study.RESULTS:The Metavir fibrosis scores were F3 in 35(28%) and F4 in 90(72%) of the patients.In total,62.9% of the patients were null-responders and 37.1% relapsers to the previous PR therapy.The overall SVR rate at 24 wk post-treatment withdrawal was 59.8%.The SVR was 65.9% in the TPV group and 44.1% in the BOC group.Independent predictive factors of an SVR included a response to previous treatment,relapsers vs null-responders [OR = 3.9;(1.4,10.6),P = 0.0084],a rapid virological response(RVR) [OR 6.9(2.6,18.2),P = 0.001] and liver stiffness lower than 21.3 kPa [OR = 8.2(2.3,29.5),P = 0.001].During treatment,63 patients(50.8%) had at least one severe adverse event(SAE) of grade 3 or 4.A multivariate analysis identified two factors associated with SAEs:female gender [OR = 2.4(1.1,5.6),P = 0.037] and a platelet count below 150 × 103/ mm3 [OR = 5.3(2.3,12.4),P ≤ 0.001].CONCLUSION:More than half of these difficult-to-treat patients achieved an SVR and had SAEs in an actual practice setting.The SVR rate was influenced by the response to previous PR treatment,the RVR and liver stiffness.     

Mouse model systems to study sex chromosome genes and behavior: Relevance to humans

Sex chromosome genes directly influence sex differences in behavior. The discovery of the Sry gene on the Y chromosome ( and ) substantiated the sex chromosome mechanistic link to sex differences. Moreover, the pronounced connection between X chromosome gene mutations and mental illness produces a strong sex bias in these diseases. Yet, the dominant explanation for sex differences continues to be the gonadal hormones. Here we review progress made on behavioral differences in mouse models that uncouple sex chromosome complement from gonadal sex. We conclude that many social and cognitive behaviors are modified by sex chromosome complement, and discuss the implications for human research. Future directions need to include identification of the genes involved and interactions with these genes and gonadal hormones.     

Usefulness of circulating biomarkers for the prediction of left ventricular remodeling after myocardial infarction

Left ventricular (LV) remodeling after myocardial infarction (MI) indicates a high risk of heart failure and death, but LV remodeling remains difficult to predict. Biomarkers may help to refine risk stratification for a more personalized medical approach. They may also shed light on the pathophysiologic processes involved. We performed a systematic review of the published evidence about the association of circulating biomarkers with LV remodeling after MI. We selected 59 publications. Overall, these studies examined 112 relations between 52 different biomarkers and LV remodeling. The biomarkers most consistently associated with LV remodeling were involved in extracellular matrix turnover or neurohormonal activation: matrix metalloproteinase-9, collagen peptides, and B-type natriuretic peptide. This review underscores the vitality of the research on LV remodeling but concludes that the ideal biomarker has not yet been identified. To reach this goal, future studies will have to be larger, have standardized imaging end points, and include replication populations to define optimal cutoffs for LV remodeling prediction. Cardiovascular magnetic resonance appears to be the best technique for LV remodeling assessment but its current availability may be a concern for recruitment for multicenter studies. Recent technologic advances will probably yield new candidate biomarkers of LV remodeling. Tests are necessary to determine whether a multimarker approach would significantly improve risk prediction.     

Validation of a short food frequency questionnaire to evaluate nutritional lifestyles in hypercholesterolemic patients

ObjectivesThe purpose of our study was to develop and validate a short food frequency questionnaire which could assess the nutritional lifestyles of hypercholesterolemic patients consulting in daily practice.Material and methodsThe questionnaire explores 11 nutrient categories. Hundred and thirty-one patients were recruited for the construct validity and 58 patients for the external validity in La Pitié Hospital, Paris. The reference method used was the diet history. To measure the internal consistency and to test the sensibility to change on a large scale, the questionnaire was used in an observational study conducted in Spain in 1048 moderate hypercholesterolemic patients. Psychometric analyses included construct validity, internal consistency, test-retest reliability, external validity and sensibility to change.ResultsValidation of the questionnaire indicated a good internal consistency (Cronbach Coefficient Alpha at 0.69) and test-retest reliability (intraclass correlation coefficient = 0.89). The correlation between the scores of the FFQ and those of the diet history was significant with a Pearson correlation coefficient at 0.3 (P = 0.029). The comparison between the ranking of the patients showed an agreement of 72% with a kappa of 0.48 [0.10; 0.69]. The sensibility to change was good with a score evolution improving one and four months after nutrition advices: 28.2% of patients ranked in group 1 at inclusion versus 61.3% (P < 0.0001) at one month and 75.2% (P < 0.0001) at four months.ConclusionIn conclusion, we developed and validated a food questionnaire for hypercholesterolemic patients, which can be used as a therapeutic education tool in daily practice or in clinical research.