Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women.

BACKGROUND: The incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda. METHODS: In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion. RESULTS: A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P=0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P=0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified. CONCLUSIONS: Among women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo. (Funded by the International Partnership for Microbicides; ClinicalTrials.gov number, NCT01539226 .)

Prevalence and Correlates of Family Meals among Families of 3rd Graders

Introduction: Dietary intake has a significant role in promoting health and preventing disease. Family meals have been associated with higher nutrient intake, lower obesity rates, and other social benefits, yet little is known about what influences family meal frequency. Methods: We examined psychosocial and demographic factors potentially related to eating dinner together among families of third graders (N=1474) participating in “Hi5+,” a family- and schoolbased nutrition program. Families were recruited from 33 schools to participate in a randomized trial to evaluate the efficacy of a fruit and vegetable promotion program.Results: Hierarchical sequential multiple regression identified nine independent variables that contributed significantly to predicting the frequency of family dinners. Meal-planning capability was the strongest&nbsp; predictor, followed by an increased number of children in the household, lower income bracket, being White, and mothers who are not externally employed, want the family to eat together, monitor their child’s intake, strongly encourage fruit and vegetable intake, and are satisfied with their family’s current fruit and vegetable intake. Conclusions: Given the importance of diet in preventing obesity and many of the leading causes of death, the importance of the family in shaping future health behaviors among youth, and the influence of family practice physicians in encouraging and reinforcing caregiver behaviors, physician efforts to encourage meal planning and support family meals among their patients are warranted. These findings can have important implications for efforts to intervene before the shift to adolescence where both family meals and vegetable intake become less frequent.</p

Identifying predictors of HPV‐related head and neck squamous cell carcinoma progression and survival through patient‐derived models

Therapeutic innovation for human papilloma virus-related (HPV+) head and neck squamous cell carcinomas (HNSCCs) is impaired by inadequate preclinical models and the absence of accurate biomarkers. Our study establishes the first well-characterized panel of patient-derived xenografts (PDXs) and organoids from HPV+ HNSCCs while determining fidelity of the models to the distinguishing genetic features of this cancer type. Despite low engraftment rates, whole exome sequencing showed that PDXs retain multiple distinguishing features of HPV+ HNSCC lost in existing cell lines, including PIK3CA mutations, TRAF3 deletion and the absence of EGFR amplifications. Engrafted HPV+ tumors frequently contained NOTCH1 mutations, thus providing new models for a negatively prognostic alteration in this disease. Genotype-phenotype associations in the models were then tested for prediction of tumor progression and survival in published clinical cohorts. Observation of high tumor mutational burdens (TMBs) in the faster-growing models facilitated identification of a novel association between TMB and local progression in both HPV+ and HPV- patients that was prognostic in HPV- cases. In addition, reduced E7 and p16INK4A levels found in a PDX from an outlier case with lethal outcome led to detection of similar profiles among recurrent HPV+ HNSCCs. Transcriptional data from the Cancer Genome Atlas was used to demonstrate that the lower E2F target gene expression predicted by reduced E7 levels has potential as a biomarker of disease recurrence risk. Our findings bridge a critical gap in preclinical models for HPV+ HNSCCs and simultaneously reveal novel potential applications of quantifying mutational burden and viral oncogene functions for biomarker development

Resilience in Louisiana FEMA Parks: A Person-Centered, Fuzzy-Set Analysis

Despite living in difficult and socially disorganized conditions, some individuals displaced by disasters and living in FEMA parks can be remarkably resilient to depression. We conceptualize resilience as emerging from a combination of situational advantages that accrue for some residents but not for others. We assess whether situational advantages lead to resilience, either in isolation or in combination with one another, in two parts. First, we used a delimited person-centered analysis (PCA) to identify advantages present among the most resilient and absent among the least resilient FEMA park residents. Second, we used fuzzy-set analysis (FSA) to systematically uncover advantageous individual-level conditions that were consistent among resilient individuals using the full sample of FEMA park respondents. Implications for sociological theory and disaster mental health research are discussed. © 2014 Copyright Taylor and Francis Group, LLC