Baseline RASs in NS5A have minimal effects on patient responses to ledipasvir/sofosbuvir therapy. When these RASs do have effects, they could be largely overcome by extending treatment duration or through treatment intensification.

Historically, clinical trials of regimens to treat chronic infection with hepatitis C virus (HCV) have used, as their primary efficacy endpoint, a sustained virological response (SVR)-defined as HCV RNA levels below a designated threshold of quantification-24 weeks after the end of treatment (SVR24). More recently, regulatory authorities have begun to accept SVR at 12 weeks post-treatment (SVR12) as a valid efficacy endpoint because of its high rate of concordance with SVR24. However, the concordance between SVR12 and SVR24 has not been systematically assessed with new regimens of recently approved directacting antiviral agents. The aim of this study was to assess the concordance between SVR at various post-treatment time points in phase III clinical trials of sofosbuvir (SOF)-containing regimens. We conducted a retrospective analysis of five trials enrolling 863 patients infected with HCV genotypes 1-6. The concordance between SVR at 4 weeks post-treatment (SVR4) and SVR12, and between SVR12 and SVR24, were determined, as well as positive predictive values (PPVs) and negative predictive values (NPVs). Overall, 779 of 796 patients (98.0%) with an SVR4 also achieved an SVR12, making the PPV of SVR4 for SVR12 98% and the NPV 100%. Of the 779 patients with an SVR12, 777 (99.7%) also achieved an SVR24, making the PPV of SVR12 for SVR24 >99% and the NPV 100%. Of patients who relapsed posttherapy, 77.6% did so within 4 weeks of completing therapy. Conclusion: Data from phase III studies demonstrate that with SOF-based regimens, with or without interferon, SVR12 and SVR24 correlate closely. Thus, SVR12 can be used effectively to determine "cure" rates in trials and in clinical practice. (HEPATOLOGY 2015;61:41-45)

Objectives Corporal punishment is still widely practiced around the globe, despite the large body of child development research that substantiates its short- and long-term consequences. Within this context, this paper examined the relationship between parental use of corporal punishment and youth externalizing behavior with a Chilean sample to add to the growing empirical evidence concerning the potential relationship between increased corporal punishment and undesirable youth outcomes across cultures. Methods Analysis was based on 919 adolescents in Santiago, Chile. Descriptive and multivariate analyses were conducted to examine the extent to which parents’ use of corporal punishment and positive family measures were associated with youth externalizing behavior. Furthermore, the associations between self-reported externalizing behavior and infrequent, as well as frequent, use of corporal punishment were investigated to contribute to understanding how varying levels of parental use of corporal punishment were differently related to youth outcomes. Results Both mother’s and father’s use of corporal punishment were associated with greater youth externalizing behavior. Additionally, increases in positive parenting practices, such as parental warmth and family involvement, were met with decreases in youth externalizing behavior when controlling for youth demographics, family socioeconomic status, and parents’ use of corporal punishment. Finally, both infrequent and frequent use of corporal punishment were positively associated with higher youth problem behaviors, though frequent corporal punishment had a stronger relationship with externalizing behavior than did infrequent corporal punishment. Conclusions Parental use of corporal punishment, even on an occasional basis, is associated with greater externalizing behavior for youth while a warm and involving family environment may protect youth from serious problem behaviors. Therefore, findings of this study add to the growing evidence concerning the negative consequences of corporal punishment for youth outcomes.

Neighborhood and parenting influences on early behavioral outcomes are strongly dependent upon a child's stage of development. However, little research has jointly considered the longitudinal associations of neighborhood and parenting processes with behavior problems in early childhood. To address this limitation, this study explores the associations of neighborhood collective efficacy and maternal corporal punishment with the longitudinal patterns of early externalizing and internalizing behavior problems. The study sample consisted of 3,705 families from a nationally representative cohort study of urban families. Longitudinal multilevel models examined the associations of collective efficacy and corporal punishment with behavior problems at age 3, as well as with patterns of behavior problems between the ages 3 to 5. Interactions between the main predictors and child age tested whether neighborhood and parent relationships with child behavior varied over time. Mediation analysis examined whether neighborhood influences on child behavior were mediated by parenting. The models controlled for a comprehensive set of possible confounders at the child, parent, and neighborhood levels. Results indicate that both maternal corporal punishment and low neighborhood collective efficacy were significantly associated with increased behavior problems. The significant interaction between collective efficacy and child age with internalizing problems suggests that neighborhood influences on internalizing behavior were stronger for younger children. The indirect effect of low collective efficacy on behavior problems through corporal punishment was not significant. These findings highlight the importance of multilevel interventions that promote both neighborhood collective efficacy and non-physical discipline in early childhood.

This study employed fixed effects regression that controls for selection bias, omitted variables bias, and all time-invariant aspects of parent and child characteristics to examine the simultaneous associations between neighborhood disorganization, maternal spanking, and aggressive behavior in early childhood using data from the Fragile Families and Child Wellbeing Study (FFCWS). Analysis was based on 2,472 children and their mothers who participated in Wave 3 (2001-2003; child age 3) and Wave 4 (2003-2006; child age 5) of the FFCWS. Results indicated that higher rates of neighborhood crime and violence predicted higher levels of child aggression. Maternal spanking in the past year, whether frequent or infrequent, was also associated with increases in aggressive behavior. This study contributes statistically rigorous evidence that exposure to violence in the neighborhood as well as the family context are predictors of child aggression. We conclude with a discussion for the need for multilevel prevention and intervention approaches that target both community and parenting factors.

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Level IV-retrospective study.