Early-stage studies to larger-scale trials: investigators' perspectives on scaling-up childhood obesity interventions.

BACKGROUND: Pilot/feasibility studies play an important role in the development and refinement of behavioral interventions by providing information about feasibility, acceptability, and potential efficacy. Despite their importance and wide-spread use, the approaches taken by behavioral scientists to scale-up early-stage studies to larger-scale trials has received little attention. The aim of our study was to understand the role that pilot studies play in the development and execution of larger-scale trials. METHODS: We conducted interviews with childhood obesity researchers who had published pilot behavioral interventions and larger-scale trials of the same or similar interventions. Questions were asked about the role of pilot studies in developing larger-scale trials and the challenges encountered when scaling-up an intervention based upon pilot findings. Data were coded and analyzed using an inductive analytic approach to identify themes. RESULTS: Twenty-four interventionists (54% women, 37-70 years old, mean 20 years since terminal degree) completed a total of 148 pilot studies across their careers (mean 6.4, range 1-20), of which 59% were scaled-up. Scaling was described as resource intensive and pilot work was considered essential to successfully competing for funding by 63% of the sample (n = 15). When asked to define a high-quality pilot study, interventionists described studies that allowed them to evaluate two independent factors: components of their intervention (e.g., acceptability, feasibility) and study parameters (e.g., sample size, measures). Interventionists expressed that more process implementation measures, different study designs, and additional iterations could improve decisions to scale-up. Most agreed that pilot studies were likely to produce inflated estimates of potential efficacy though only nine interventionists provided potential solutions for decreasing inflated measures of efficacy. Suggested major causes of inflated effects included high levels of oversight in pilot studies (e.g., researcher support), reliance on subjective measures, and utilizing convenience or highly motivated samples. Potential solutions included designing pilots for real-world implementation, only conducting randomized controlled pilot studies, and pre-registering pilot studies. CONCLUSIONS: Pilot studies purposes are multifaceted and deemed essential to obtaining funding for larger-scale trials. Clarifying the form and function of preliminary, early-stage research may enhance the productive utilization of early-stage studies and reduced drops in efficacy when transitioning to larger scale studies.

The impact of summer vacation on children's obesogenic behaviors and body mass index: a natural experiment.

BACKGROUND: Children's BMI gain accelerates during summer. The Structured Days Hypothesis posits that the lack of the school day during summer vacation negatively impacts children's obesogenic behaviors (i.e., physical activity, screen time, diet, sleep). This natural experiment examined the impact of summer vacation on children's obesogenic behaviors and body mass index (BMI). METHODS: Elementary-aged children (n = 285, 5-12 years, 48.7% male, 57.4% African American) attending a year-round (n = 97) and two match-paired traditional schools (n = 188) in the United States participated in this study. Rather than taking a long break from school during the summer like traditional schools, year-round schools take shorter and more frequent breaks from school. This difference in school calendars allowed for obesogenic behaviors to be collected during three conditions: Condition 1) all children attend school, Condition 2) year-round children attend school while traditional children were on summer vacation, and Condition 3) summer vacation for all children. Changes in BMI z-score were collected for the corresponding school years and summers. Multi-level mixed effects regressions estimated obesogenic behaviors and monthly zBMI changes. It was hypothesized that children would experience unhealthy changes in obesogenic behaviors when entering summer vacation because the absence of the school day (i.e., Condition 1 vs. 2 for traditional school children and 2 vs. 3 for year-round school children). RESULTS: From Condition 1 to 2 traditional school children experienced greater unhealthy changes in daily minutes sedentary (∆ = 24.2, 95CI = 10.2, 38.2), screen time minutes (∆ = 33.7, 95CI = 17.2, 50.3), sleep midpoint time (∆ = 73:43, 95CI = 65:33, 81:53), and sleep efficiency percentage (-∆ = 0.7, 95CI = -1.1, - 0.3) when compared to year-round school children. Alternatively, from Condition 2 to 3 year-round school children experienced greater unhealthy changes in daily minutes sedentary (∆ = 54.5, 95CI = 38.0, 70.9), light physical activity minutes (∆ = - 42.2, 95CI = -56.2, - 28.3) MVPA minutes (∆ = - 11.4, 95CI = -3.7, - 19.1), screen time minutes (∆ = 46.5, 95CI = 30.0, 63.0), and sleep midpoint time (∆ = 95:54, 95CI = 85:26, 106:22) when compared to traditional school children. Monthly zBMI gain accelerated during summer for traditional (∆ = 0.033 95CI = 0.019, 0.047) but not year-round school children (∆ = 0.004, 95CI = -0.014, 0.023). CONCLUSIONS: This study suggests that the lack of the school day during summer vacation negatively impacts sedentary behaviors, sleep timing, and screen time. Changes in sedentary behaviors, screen time, and sleep midpoint may contribute to accelerated summer BMI gain. Providing structured programming during summer vacation may positively impact these behaviors, and in turn, mitigate accelerated summer BMI gain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03397940 . Registered January 12th 2018.

The impact of summer programming on the obesogenic behaviors of children: behavioral outcomes from a quasi-experimental pilot trial.

BACKGROUND: Children from low-income families experience accelerated BMI gain and learning loss during summer. Healthy Summer Learners (HSL) addresses accelerated BMI gain and academic learning loss during summer by providing academic- and health-focused programming. This manuscript reports the effects of HSL on underlying obesogenic behaviors (i.e., physical activity, screen time, sleep, diet) that lead to accelerated summer BMI gain, a necessary first step to informing a future randomized controlled trial of HSL. METHODS: In the summer of 2018 and 2019 using a quasi-experimental study design, 180 children (90 per summer, 7.9 years [SD = 1.0], 94% non-Hispanic Black, 40% male) at two schools (i.e., one per summer) who were struggling academically (25-75% on a standardized reading test) were provided a free, school-based 6-week health- and academic-focused summer program (i.e., HSL, n = 60), a 4- to 6-week academic-focused summer program (i.e., 21st Century Summer Learning program (21C), n = 60), or no summer program (n = 60). Children wore the Fitbit Charge 2™ over a 10-week period during the summers (June-Aug) of 2018-2019. Differences within (within child days attend vs. not attend) and between (differences between groups attend vs. not attend) were evaluated using mixed effects linear regression. RESULTS: Regression estimates indicated that, on days attending, HSL children experienced a greater reduction in sedentary minutes (- 58.6 [95% CI = - 92.7, - 24.4]) and a greater increase in moderate-to-vigorous physical activity (MVPA) (36.2 [95% CI = 25.1, 47.3]) and steps (2799.2 [95% CI = 2114.2, 3484.2]) compared to 21C children. However, both HSL and 21C children were more active (i.e., greater MVPA, total steps) and less sedentary (i.e., less sedentary minutes and total screen time) and displayed better sleeping patterns (i.e., earlier and less variability in sleep onset and offset) on days they attended than children in the control. CONCLUSIONS: HSL produced greater changes in physical activity than 21C. However, attendance at either HSL or 21C leads to more healthy obesogenic behaviors. Based on the behavioral data in this pilot study, a larger trial may be warranted. These results must be considered along with the pending primary outcomes (i.e., academics and BMI z-score) of the HSL pilot to determine if a full-scale trial is warranted. TRIAL REGISTRATION: NIH-NCT03321071. Registered 25 October 2017.

Raised cerebrospinal fluid norepinephrine in some patients with primary hypertension.

To test whether central neurogenic factors participate in blood pressure elevation in primary hypertension, we studied the concentrations of: norepinephrine, epinephrine and dopamine-beta-hydroxylase (DBH) in cerebrospinal fluid (CSF); and norepinephrine, epinephrine, DBH and plasma renin activity (PRA) in plasma of 22 subjects (seven with primary hypertension, 11 normotensive patients with non-systemic neurological disorders, and four with secondary hypertension). Plasma and CSF norepinephrine (NE) were increased in primary hypertensives compared to normotensives. Cerebrospinal fluid norepinephrine was related to diastolic blood pressure, and systolic blood pressure when normotensive and primary hypertensives were taken together. The CSF norepinephrine of primary hypertensive patients was correlated with natural log PRA. The CSF norepinephrine was correlated inversely with age in primary hypertensive patients but not in the normotensive subjects. The low CSF norepinephrine and epinephrine, despite markedly increased plasma NE and epinephrine, in two patients with pheochromocytoma, indicate a blood-brain barrier for these neurohormones. The observations support the view that the central sympathetic nervous system is involved in the pathogenesis of primary hypertension, particularly in younger patients.