A comprehensive review of the impact of tacrolimus intrapatient variability on clinical outcomes in kidney transplantation.

Tacrolimus (Tac) is widely used to prevent rejection and graft loss in solid organ transplantation. A limiting characteristic of Tac is the high intra and interpatient variability associated with its use. Routine therapeutic drug monitoring (TDM) is necessary to facilitate Tac management and to avoid undesirable clinical outcomes. However, whole blood trough concentrations commonly utilized in TDM are not strong predictors of the detrimental clinical outcomes of interest. Recently, researchers have focused on Tac intrapatient variability (Tac IPV) as a novel marker to better assess patient risk. Higher Tac IPV has been associated with a number of mechanisms leading to shortened graft survival. Medication nonadherence (MNA) is considered to be the primary determinant of high Tac IPV and perhaps the most modifiable risk factor. An understanding of the methodology behind Tac IPV is imperative to its recognition as an important prognostic measure and integration into clinical practice. Therapeutic interventions targeting MNA and reducing Tac IPV are crucial to improving long-term graft survival.

Exploratory Analysis of the Impact of an mHealth Medication Adherence Intervention on Tacrolimus Trough Concentration Variability: Post Hoc Results of a Randomized Controlled Trial.

BACKGROUND: Medication nonadherence is a leading cause of late allograft loss in kidney transplantation (KT). Tacrolimus trough coefficient of variation (CV), measured using the coefficient of variation, is strongly correlated with acute rejection, graft function, and graft loss. OBJECTIVE: The objective of this study was to determine if this mobile health (mHealth) intervention aimed at improving medication adherence in a nonadherent KT population would affect high intrapatient tacrolimus variability. METHODS: A 6-month, prospective, parallel-arm, randomized controlled clinical trial was conducted to determine the effects of an mHealth intervention on tacrolimus CV. Intervention arm participants utilized an electronic medication tray and an mHealth app to monitor home-based adherence. Tailored motivational reinforcement messages were delivered to promote competence for adherence. Tacrolimus CV was measured using a 12-month rolling average, assessed at monthly intervals (6-month intervention period and 6 months after completion of the study); 80 were included, 40 in each arm. RESULTS: At baseline, tacrolimus CV was similar between arms (37% ± 15% intervention, 37% ± 13% control, P = 0.894). Patients randomized to the intervention had a significant reduction in mean 12-month tacrolimus CVs (P = 0.046) and a significant improvement in the proportion achieving low tacrolimus CV (tacrolimus CV < 40%; P = 0.001), as compared with the control arm. CONCLUSION AND RELEVANCE: High tacrolimus CV is a risk factor for acute rejection and graft loss; these results offer the potential promise of improved medication adherence and clinical outcomes through the use of innovative technology.

Converting between estimates of moderate-to-vigorous physical activity derived from raw accelerations measured at the wrist and from ActiGraph counts measured at the hip: the Rosetta Stone.

The ability to compare published group-level estimates of objectively measured moderate-to-vigorous physical activity (MVPA) across studies continues to increase in difficulty. The objective of this study was to develop conversion equations and demonstrate their utility to compare estimates of MVPA derived from the wrist and hip. Three studies of youth (N = 232, 9-12yrs, 50% boys) concurrently wore a hip-worn ActiGraph and a wrist-worn GENEActiv for 7-days. ActiGraph hip count data were reduced using four established cutpoints. Wrist accelerations were reduced using the Hildebrand MVPA 200 mg threshold. Conversion equations were developed on a randomly selected subsample of 132 youth. Equations were cross-validated and absolute error, absolute percent error, and modified Bland-Altman plots were evaluated for conversion accuracy. Across equations R2adj was 0.51-0.56 with individual-level absolute error in minutes ranging from 7 (wrist-to-hip Puyau) to 14.5 minutes (wrist-to-hip Freedson 3MET) and absolute percent differences ranging from 13.9%-24.5%. Group-level cross-validation to convert hip-to-wrist MVPA resulted in average absolute percent errors ranging from 3.1%-4.9%. Conversion of wrist-to-hip MVPA resulted in average absolute percent errors ranging from 3.0%-10.0%. We recommend the use of these equations to compare published estimates of MVPA between the wear-site cut-point combinations presented.

Understanding differences between summer vs. school obesogenic behaviors of children: the structured days hypothesis.

BACKGROUND: Although the scientific community has acknowledged modest improvements can be made to weight status and obesogenic behaviors (i.e., physical activity, sedentary/screen time, diet, and sleep) during the school year, studies suggests improvements are erased as elementary-age children are released to summer vacation. Emerging evidence shows children return to school after summer vacation displaying accelerated weight gain compared to the weight gained occurring during the school year. Understanding how summer days differ from when children are in school is, therefore, essential. DISCUSSION: There is limited evidence on the etiology of accelerated weight gain during summer, with few studies comparing obesogenic behaviors on the same children during school and summer. For many children, summer days may be analogous to weekend days throughout the school year. Weekend days are often limited in consistent and formal structure, and thus differ from school days where segmented, pre-planned, restrictive, and compulsory components exist that shape obesogenic behaviors. The authors hypothesize that obesogenic behaviors are beneficially regulated when children are exposed to a structured day (i.e., school weekday) compared to what commonly occurs during summer. This is referred to as the 'Structured Days Hypothesis' (SDH). To illustrate how the SDH operates, this study examines empirical data that compares weekend day (less-structured) versus weekday (structured) obesogenic behaviors in U.S. elementary school-aged children. From 190 studies, 155 (~80%) demonstrate elementary-aged children's obesogenic behaviors are more unfavorable during weekend days compared to weekdays. CONCLUSION: In light of the SDH, consistent evidence demonstrates the structured environment of weekdays may help to protect children by regulating obesogenic behaviors, most likely through compulsory physical activity opportunities, restricting caloric intake, reducing screen time occasions, and regulating sleep schedules. Summer is emerging as the critical period where childhood obesity prevention efforts need to be focused. The SDH can help researchers understand the drivers of obesogenic behaviors during summer and lead to innovative intervention development.

The Association Between Physical Performance and Executive Function in a Sample of Rural Older Adults from South Carolina, USA.

BACKGROUND: Mobility and executive functions (EFs) decline with age, although associations between mobility and EFs are less clear. This study examined relationships between different mobility measures and EFs among rural older adults. METHODS: This cross-sectional study recruited 56 older adults (60+ years) in rural South Carolina. Mobility was assessed via gait speed, timed up-and-go, chair stand, and as a composite physical performance score (PPS). EFs was assessed via Trail Making Test, semantic fluency, and phonemic fluency. Bivariate analyses were performed and regressions were calculated controlling for appropriate covariates, with PPS as the independent variable and each EF test as the dependent variable. RESULTS: Mean age was 74.22 years (SD = 8.02), 80.40% were female and 64.71% were white. Bivariate analysis revealed associations between gait speed and Trail Making Test (r = -.33; p = .03), between timed up-and-go and Trail Making Test (r = .34; p = .01), and between PPS and Trail Making Test (r = -.33; p = .03). The regression models indicated higher PPS was associated with better performance on Trail Making Test (ß = -1.12; p < 0.01), phonemic fluency (ß = 0.68; p = .01), and semantic fluency (ß = 0.81; p = .02). CONCLUSIONS: In a rural setting, mobility is associated with multiple EF processes. Higher mobility and physical ability are desired for maintaining EFs capability.

Maximizing children's physical activity using the LET US Play principles.

BACKGROUND: Staff in settings that care for children struggle to implement standards designed to promote moderate-to-vigorous physical activity (MVPA), suggesting a need for effective strategies to maximize the amount of time children spend in MVPA during scheduled PA opportunities. The purpose of this study was to compare the MVPA children accumulate during commonly played games delivered in their traditional format versus games modified according to the LET US Play principles. METHODS: Children (K-5th) participated in 1-hour PA sessions delivered on non-consecutive days (summer 2014). Using a randomized, counterbalanced design, one of the six games was played for 20min using either traditional rules or LET US Play followed by the other strategy with a 10min break in between. Physical activity was measured via accelerometry. Repeated-measures, mixed-effects regression models were used to estimate differences in percent of time spent sedentary and in MVPA. RESULTS: A total of 267 children (age 7.5years, 43% female, 29% African American) participated in 50, 1-hour activity sessions. Games incorporating LET US Play elicited more MVPA from both boys and girls compared to the same games with traditional rules. For boys and girls, the largest MVPA difference occurred during tag games (+20.3%). The largest reduction in the percent of time sedentary occurred during tag games (boys -27.7%, girls -32.4%). Overall, the percentage of children meeting 50% time in MVPA increased in four games (+18.7% to +53.1%). CONCLUSION: LET US Play led to greater accumulation of MVPA for boys and girls, and can increase the percent of children attaining the 50% of time in MVPA standard.

The application of mHealth to monitor implementation of best practices to support healthy eating and physical activity in afterschool programs.

BACKGROUND: Childhood obesity continues to be a global epidemic and many child-based settings (e.g. school, afterschool programs) have great potential to make a positive impact on children's health behaviors. Innovative and time-sensitive methods of gathering health behavior information for the purpose of evaluation and strategically deploying support are needed in these settings. PURPOSE: The aim is to (1) demonstrate the feasibility of mobile health (mHealth) for monitoring implementation of healthy eating and physical activity (HEPA) standards and, (2) illustrate the utility of mHealth for identifying areas where support is needed, within the afterschool setting. METHODS: Site leaders (N = 175) of afterschool programs (ASPs) were invited to complete an online observation checklist via a mobile web app (Healthy Eating and Physical Activity Mobile, HEPAm) once per week during ASP operating hours. Auto-generated weekly text reminders were sent to site leaders' mobile devices during spring and fall 2015 and 2016 and spring 2017 school semesters. Data from HEPAm was separated into HEPA variables, and expressed as a percent of checklists where an item was present. A higher percentage for a given item would indicate an afterschool has higher compliance with current HEPA standards. RESULTS: A total of 141 site leaders of ASPs completed 13,960 HEPAm checklists. The average number of checklists completed per ASP was 43 (range 1-220) for healthy eating and 50 (range 1-230) for physical activity. For healthy eating, the most common challenge for ASPs was 'Staff educating children about healthy eating', and for physical activity checklists, 'Girls only physical activity is provided at ASP'. CONCLUSION: HEPAm was widely used and provided valuable information that can be used to strategically deploy HEPA support to ASPs. This study gives confidence to the adoption of mHealth strategies as a means for public health practitioners to monitor compliance of an initiative or intervention.

Structure of Physical Activity Opportunities Contribution to Children's Physical Activity Levels in After-School Programs.

BACKGROUND: The primary purpose of this study was to determine which physical activity (PA) opportunity elicits the most moderate to vigorous PA (MVPA) in after-school programs. This study used a 3-group cross-over design in which participants were exposed to 3 variations of activity structures: free play, organized, or a mixture. METHODS: PA was measured using ActiGraph GT3X+ accelerometers. All data were transformed into percentage of time spent sedentary or in MVPA. Repeated-measures mixed-effects models were used to examine differences in MVPA and sedentary among the 3 activity sessions. Participants included 197 unique children, aged 5-12 years, and were 53% male and 55% white. RESULTS: Statistically significant differences were observed in the percentage of time boys spent in MVPA during free play and mixed compared with organized only sessions (35.8% and 34.8% vs 29.4%). No significant difference was observed in the percentage of time girls spent in MVPA during free play compared with organized or mixed (27.2% and 26.1% vs 26.1%). Both boys and girls experienced ∼10% less time sedentary during free play compared with the others. CONCLUSION: Offering free play during PA opportunities can help children attain as much if not more MVPA compared with only offering organized, adult-led games.

Children's Moderate to Vigorous Physical Activity Attending Summer Day Camps.

INTRODUCTION: National physical activity standards call for all children to accumulate 60 minutes/day of moderate to vigorous physical activity (MVPA). The contribution of summer day camps toward meeting this benchmark is largely unknown. The purpose of this study was to provide estimates of children's MVPA during summer day camps. METHODS: Children (n=1,061, 78% enrollment; mean age, 7.8 years; 46% female; 65% African American; 48% normal weight) from 20 summer day camps wore ActiGraph GT3x+ accelerometers on the wrist during camp hours for up to 4 non-consecutive days over the summer of 2015 (July). Accumulated MVPA at the 25th, 50th, and 75th percentile of the distribution was estimated using random-effects quantile regression. All models were estimated separately for boys and girls and controlled for wear time. Minutes of MVPA were dichotomized to ≥60 minutes/day of MVPA or <60 minutes/day to estimate percentage of boys and girls meeting the 60 minutes/day guideline. All data were analyzed in spring 2016. RESULTS: Across the 20 summer day camps, boys (n=569) and girls (n=492) accumulated a median of 96 and 82 minutes/day of MVPA, respectively. The percentage of children meeting 60 minutes/day of MVPA was 80% (range, 41%-94%) for boys and 73% (range, 30%-97%) for girls. CONCLUSIONS: Summer day camps are a setting where a large portion of boys and girls meet daily physical activity guidelines. Public health practitioners should focus efforts on making summer day camps accessible for children in the U.S.

First year physical activity findings from turn up the HEAT (Healthy Eating and Activity Time) in summer day camps.

BACKGROUND: Summer day camps (SDCs) serve 14 million children yearly in the U.S. and aim to provide participating children with 60 minutes of moderate-to-vigorous physical activity (MVPA). This study evaluated an intervention designed to increase the percent of children meeting this MVPA guideline. DESIGN: Two-group, pre-post quasi-experimental. SETTING/PARTICIPANTS: Twenty SDCs serving 1,830 children aged 5-12 years were assigned to MVPA intervention (n = 10) or healthy eating attention control (n = 10). INTERVENTION: The STEPs (Strategies to Enhance Practice) intervention is a capacity-building approach grounded in the Theory of Expanded, Extended and Enhanced Opportunities. Camp leaders and staff receive training to expand (e.g., introduction of activity breaks/active field trips), extend (e.g., schedule minimum of 3 hours/day for PA opportunities), and enhance (e.g., maximize MVPA children accumulate during schedule activity) activity opportunities. Camps in the comparison condition received support for improving the types of foods/beverages served. MAIN OUTCOME MEASURES: Percent of children accumulating the 60min/d MVPA guideline at baseline (summer 2015) and post-test (summer 2016) measured via wrist-accelerometry. RESULTS: Multilevel logistic regression conducted fall 2016 indicated boys and girls attending intervention SDCs were 2.04 (95CI = 1.10,3.78) and 3.84 (95CI = 2.02,7.33) times more likely to meet the 60min/d guideline compared to boys and girls attending control SDCs, respectively. This corresponded to increases of +10.6% (78-89%) and +12.6% (69-82%) in the percentage of boys and girls meeting the guideline in intervention SDCs, respectively. Boys in comparison SDCs increased by +1.6% (81-83%) and girls decreased by -5.5% (76-71%). Process data indicated intervention SDCs successfully extended and enhanced PA opportunities, but were unable to expand PA opportunities, compared to control SDCs. CONCLUSIONS: Although substantial proportions of children met the MVPA guideline at baseline, no SDCs ensured all children met the guideline. This intervention demonstrated that, with support, SDCs can help all children in attendance to accumulate their daily recommended 60min MVPA. TRIAL REGISTRATION: ClinicalTrials.gov NCT02161809.

Equating accelerometer estimates among youth: The Rosetta Stone 2.

OBJECTIVES: Different accelerometer cutpoints used by different researchers often yields vastly different estimates of moderate-to-vigorous intensity physical activity (MVPA). This is recognized as cutpoint non-equivalence (CNE), which reduces the ability to accurately compare youth MVPA across studies. The objective of this research is to develop a cutpoint conversion system that standardizes minutes of MVPA for six different sets of published cutpoints. DESIGN: Secondary data analysis. METHODS: Data from the International Children's Accelerometer Database (ICAD; Spring 2014) consisting of 43,112 Actigraph accelerometer data files from 21 worldwide studies (children 3-18 years, 61.5% female) were used to develop prediction equations for six sets of published cutpoints. Linear and non-linear modeling, using a leave one out cross-validation technique, was employed to develop equations to convert MVPA from one set of cutpoints into another. Bland Altman plots illustrate the agreement between actual MVPA and predicted MVPA values. RESULTS: Across the total sample, mean MVPA ranged from 29.7MVPAmind(-1) (Puyau) to 126.1MVPAmind(-1) (Freedson 3 METs). Across conversion equations, median absolute percent error was 12.6% (range: 1.3 to 30.1) and the proportion of variance explained ranged from 66.7% to 99.8%. Mean difference for the best performing prediction equation (VC from EV) was -0.110mind(-1) (limits of agreement (LOA), -2.623 to 2.402). The mean difference for the worst performing prediction equation (FR3 from PY) was 34.76mind(-1) (LOA, -60.392 to 129.910). CONCLUSIONS: For six different sets of published cutpoints, the use of this equating system can assist individuals attempting to synthesize the growing body of literature on Actigraph, accelerometry-derived MVPA.