Our group has recently demonstrated that chimeric antigen receptor T-cell therapy targeting the CD30 antigen (CD30.CAR-T) is highly effective in patients with relapsed and refractory (r/r) classical Hodgkin lymphoma (cHL). Despite high rates of clinical response, relapses and progression were observed in a subset of patients. The objective of this study was to characterize clinical and correlative factors associated with progression-free survival (PFS) after CD30.CAR-T cell therapy. We evaluated correlatives in 27 patients with r/r cHL treated with lymphodepletion and CD30.CAR-T cells. With a median follow-up of 9.5 months, 17 patients (63%) progressed, with a median PFS of 352 days (95% confidence interval: 116-not reached), and 2 patients died (7%) with a median overall survival of not reached. High metabolic tumor volume (MTV, >60 mL) immediately before lymphodepletion and CD30.CAR-T cell infusion was associated with inferior PFS (log rank, P = .02), which persisted after adjusting for lymphodepletion and CAR-T dose (log rank, P = .01 and P = .006, respectively). In contrast, receiving bridging therapy, response to bridging therapy, CD30.CAR-T expansion/persistence, and percentage of CD3+PD-1+ lymphocytes over the first 6 weeks of therapy were not associated with differences in PFS. In summary, this study reports an association between high baseline MTV immediately before lymphodepletion and CD30.CAR-T cell infusion and worse PFS in patients with r/r cHL. This trial was registered at www.clinicaltrials.gov as #NCT02690545.

We aimed to examine the retention of Hispanics/Latinos participating in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a prospective cohort study of 16,415 adults in 4 US cities who were enrolled between 2008 and 2011. We summarized retention strategies and examined contact, response, and participation rates over 5 years of annual follow-up interviews. We then evaluated motivations for participation and satisfaction with retention efforts among participants who completed a second in-person interview approximately 6 years after their baseline interview. Finally, we conducted logistic regression analyses estimating associations of demographic, health, and interview characteristics at study visit 1 (baseline) with participation, high motivation, and high satisfaction at visit 2. Across 5 years, the HCHS/SOL maintained contact, response, and participation rates over 80%. The most difficult Hispanic/Latino populations to retain included young, single, US-born males with less than a high school education. At visit 2, we found high rates of motivation and satisfaction. HCHS/SOL participants primarily sought to help their community and learn more about their health. High rates of retention of Hispanics/Latinos can be facilitated through the employment of bilingual/bicultural staff and the development of culturally tailored retention materials.

Due to the many benefits of understanding treatment effect heterogeneity in a clinical trial, an exploratory post hoc subgroup analysis is often performed to find subpopulations of patients with conditional average treatment effect that suggests better treatment efficacy than in the overall population. A naive re-substitution approach uses all available data to identify a subgroup and then proceeds with estimation and inference using the same data set. This approach generally leads to an overly optimistic estimate of conditional average treatment effect. In this article, in a post hoc analysis, we estimate the target optimal subgroup through maximizing a utility function, from candidates systematically identified with a penalized regression. We then compare two resampling-based bias-correction methods, cross-validation and debiasing bootstrap, for obtaining approximately unbiased estimates and valid inference of conditional average treatment effect in the identified subgroup, with either an empirical or an augmented estimator. Our results show that both the cross-validation and the debiasing bootstrap methods reduce the re-substitution bias effectively. The cross-validation method appears to have less biased point estimates, smaller standard error estimates, but poorer coverages than the debiasing bootstrap method when using the empirical estimator and the sample size is moderate. Using the augmented estimator in the debiasing bootstrap method leads to less biased point estimates but poorer coverages. We conclude that bias correction should be a part of every exploratory post hoc subgroup analysis to eliminate re-substitution bias and to obtain a proper confidence interval for the estimated conditional average treatment effect in the selected subgroup.

BackgroundAnemia, particularly iron deficiency anemia, is still common among children from resource poor settings. Besides inadequate intake of iron rich foods, lead toxicity may be an important underlying cause for anemia and iron deficiency. However, there are lack of data on lead toxicity and its relation with anemia and iron deficiency.MethodsBlood samples were collected from 225 healthy children at 15 months of age who were participating in a cohort study on malnutrition and interaction with enteric infection (MAL‐ED). Blood was analyzed for leads hemoglobin, plasma ferritin, and transferrin receptor concentrations.ResultsThe prevalence of anemia (Hb <11 g/dl) was 51% and 54% of children were iron deficient as indicated by low ferritin and/or high transferrin receptor concentrations. The mean (SD) blood lead concentration was 12.8 μg/dl (7.6) and 60% of children were having high lead concentrations (>10 μg/dl). Sixty‐three percent of the anemic children had high blood lead concentrations compared with 56% among the non‐anemic children (p=0.2). Similarly, high lead concentration was found among 61% children with iron deficiency and in 54% of the non‐deficient (p=0.2).ConclusionAnemia, iron deficiency and high blood lead concentration was common among healthy infants in Bhaktapur. However, higher lead concentration was not associated with anemia and iron deficiency.Support or Funding InformationThe Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL‐ED) is carried out as a collaborative project supported by the Bill and Melinda Gates Foundation, The Foundations for the NIH and the National Institute of Health/ Fogarty International Center. The authors thank the staff and participants of the MAL‐ED Network Project for their important contributions.

Purpose Existing sedentary behavior interventions have largely achieved mixed results. Conventionally, interventions have attempted to reduce sedentary behavior using a full-day approach. An alternative strategy may be to target specific periods during the day and/or week. This study examined the day-of-the-week (Monday to Sunday) and time-of-the-day patterns (3-hr and 6-hr periods) of sedentary behavior among U.S. Hispanics/Latinos adults. Methods Participants (n = 12,241) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multi-site community-based prospective cohort study of Hispanic/Latino adults, were studied. Sedentary behavior was assessed for one week using a hip-mounted accelerometer through total sedentary time, sedentary time in bouts ≥60 minutes, and total number of sedentary breaks. The temporal patterns of sedentary behavior metrics were evaluated using linear mixed effect models accounting for HCHS/SOL complex survey design. Results There were statistically significant variations in temporal patterns across day-of-the-week and time-of-the-day periods for all three metrics (p < .001). Adults were more sedentary on weekends than on weekdays, and most sedentary on Sundays. The time-of-the-day patterns had a U-curve pattern wherein adults were most sedentary late at night, became less sedentary throughout the day, reached peak activeness around noon, then gradually became more sedentary into the evening. These patterns were largely robust across seasonality and most sociodemographic characteristics including age, employment status, work shift schedule, acculturation, and field center. Conclusions Our findings suggest that early mornings, evenings, and weekends were the more sedentary periods in this cohort of Hispanic/Latino adults, characterized by higher volumes of sedentary time, higher volumes of time in prolonged sedentary bouts, and fewer number of sedentary breaks than other time periods, highlighting important windows of opportunity to reduce sedentary behavior.