Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK.

BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. METHODS: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). FINDINGS: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. INTERPRETATION: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services. FUNDING: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association.

Climate change increases threat to plant diversity in tropical forests of Central America and southern Mexico.

Global biodiversity is negatively affected by anthropogenic climate change. As species distributions shift due to increasing temperatures and precipitation fluctuations, many species face the risk of extinction. In this study, we explore the expected trend for plant species distributions in Central America and southern Mexico under two alternative Representative Concentration Pathways (RCPs) portraying moderate (RCP4.5) and severe (RCP8.5) increases in greenhouse gas emissions, combined with two species dispersal assumptions (limited and unlimited), for the 2061-2080 climate forecast. Using an ensemble approach employing three techniques to generate species distribution models, we classified 1924 plant species from the region's (sub)tropical forests according to IUCN Red List categories. To infer the spatial and taxonomic distribution of species' vulnerability under each scenario, we calculated the proportion of species in a threat category (Vulnerable, Endangered, Critically Endangered) at a pixel resolution of 30 arc seconds and by family. Our results show a high proportion (58-67%) of threatened species among the four experimental scenarios, with the highest proportion under RCP8.5 and limited dispersal. Threatened species were concentrated in montane areas and avoided lowland areas where conditions are likely to be increasingly inhospitable. Annual precipitation and diurnal temperature range were the main drivers of species' relative vulnerability. Our approach identifies strategic montane areas and taxa of conservation concern that merit urgent inclusion in management plans to improve climatic resilience in the Mesoamerican biodiversity hotspot. Such information is necessary to develop policies that prioritize vulnerable elements and mitigate threats to biodiversity under climate change.

Parent factors associated with BMI, diet, and physical activity of adolescents with intellectual and developmental disabilities.

BACKGROUND: Adolescents with intellectual and developmental disabilities (IDD) experience overweight and obesity (OW/OB) up to 1.8 times the rate of their typically developing peers. Parents may influence adolescent weight management behaviors in this population, but the association between parent factors and adolescent weight management behaviors is unclear. OBJECTIVE: To examine the associations between parent BMI and sociodemographic characteristics with adolescents' BMI, diet quality, daily energy intake, moderate to vigorous physical activity (MVPA), and sedentary behavior. METHODS: This study analyzed baseline data from an 18-month randomized controlled weight loss trial for adolescents with IDD. We assessed parent BMI (kg/m2) and sociodemographic factors, and adolescent BMI z-score, MVPA, sedentary time, daily energy intake, and diet quality. Associations between parent and adolescent factors were assessed with Pearson, Spearman or Kendall Tau-b correlations; mean differences for categorical outcomes were assessed with independent samples t-tests/Mann-Whitney U tests or ANOVA/Kruskall-Wallis tests. RESULTS: Ninety-five adolescent and parent dyads were included. Parent BMI was positively correlated with adolescent BMI z-score (n = 94: rs = 0.37, p < 0.01). Household income was inversely correlated with adolescent BMI z-score (n = 95: Tb = -0.18, p = 0.02). Parents with less than a bachelor's degree had adolescents with higher BMI z-scores than those with bachelor's or higher (2.1 ± 0.5 vs. 1.8 ± 0.5, p = 0.02) as well as higher sedentary behavior (n = 28, 515.2 ± 102.6 min/day vs. n = 40, 463.9 ± 148.1 min/day, p = 0.02). CONCLUSION: We found parent BMI, income, and education associated with adolescent BMI z-score. These findings contribute to the sparse literature on parental factors associated with OW/OB in this population. CLINICAL TRIALS NUMBER: NCT02561754.

Peak Oxygen Consumption (V̇O 2peak ) Recovery Delay in a Pediatric Fontan Population.

PURPOSE: The purpose of this study is to identify predictors and correlates of VO2RD in youth with Fontan. METHODS: Cardiopulmonary exercise test data was used from a single center, cross-sectional study of children and adolescents (age, 8-21 yr) with Fontan physiology. The VO2RD was determined using time (s) to <90% of V̇O 2peak and categorized as "low" (≤10 s) or "high" (≥10 s). t Tests and χ 2 analysis were used to compare continuous and categorical variables, respectively. RESULTS: The analysis sample included 30 adolescents with Fontan physiology (age, 14.2 ± 2.4 yr; 67% male) with either right ventricular (RV) dominant (40%) or co/left ventricular (Co/LV) dominant (60%) systemic ventricular morphology. There were no differences in V̇O 2peak between the high and low VO2RD groups (high = 1.3 ± 0.4 L·min -1 ; low = 1.3 ± 0.3 L·min -1 ; P = 0.97). VO2RD in participants with RV dominance was significantly greater than in patients with Co/LV dominance (RV = 23.8 ± 15.8 s; Co/LV = 11.8 ± 16.1 s; P = 0.03). CONCLUSIONS: V̇O 2peak was not correlated with VO2RD when analyzed as high/low VO2RD groups. However, morphology of the systemic single ventricle (RV vs Co/LV) may be related to rate of recovery in V̇O 2 after a peak cardiopulmonary exercise test.

ehealth technology in cardiac exercise therapeutics for pediatric patients with congenital and acquired heart conditions: a summary of evidence and future directions.

Many children and adolescents with congenital and acquired heart disease (CHD) are physically inactive and participate in an insufficient amount of moderate-to-vigorous intensity exercise. Although physical activity (PA) and exercise interventions are effective at improving short- and long-term physiological and psychosocial outcomes in youth with CHD, several barriers including resource limitations, financial costs, and knowledge inhibit widespread implementation and dissemination of these beneficial programs. New and developing eHealth, mHealth, and remote monitoring technologies offer a potentially transformative and cost-effective solution to increase access to PA and exercise programs for youth with CHD, yet little has been written on this topic. In this review, a cardiac exercise therapeutics (CET) model is presented as a systematic approach to PA and exercise, with assessment and testing guiding three sequential PA and exercise intervention approaches of progressive intensity and resource requirements: (1) PA and exercise promotion within a clinical setting; (2) unsupervised exercise prescription; and (3) medically supervised fitness training intervention (i.e., cardiac rehabilitation). Using the CET model, the goal of this review is to summarize the current evidence describing the application of novel technologies within CET in populations of children and adolescents with CHD and introduce potential future applications of these technologies with an emphasis on improving equity and access to patients in low-resource settings and underserved communities.

Moderators of peak respiratory exchange ratio during exercise testing in children and adolescents with Fontan physiology.

OBJECTIVES: Many patients with Fontan physiology are unable to achieve the minimum criteria for peak effort during cardiopulmonary exercise testing. The purpose of this study is to determine the influence of physical activity and other clinical predictors related to achieving peak exercise criteria, signified by respiratory exchange ratio ≥ 1.1 in youth with Fontan physiology. METHODS: Secondary analysis of a cross-sectional study of 8-18-year-olds with single ventricle post-Fontan palliation who underwent cardiopulmonary exercise testing (James cycle protocol) and completed a past-year physical activity survey. Bivariate associations were assessed by Wilcoxon rank-sum test and simple regression. Conditional inference forest algorithm was used to classify participants achieving respiratory exchange ratio > 1.1 and to predict peak respiratory exchange ratio. RESULTS: Of the n = 43 participants, 65% were male, mean age was 14.0 ± 2.4 years, and 67.4% (n = 29) achieved respiratory exchange ratio ≥ 1.1. Despite some cardiopulmonary exercise stress test variables achieving statistical significance in bivariate associations with participants achieving respiratory exchange ratio > 1.1, the classification accuracy had area under the precision recall curve of 0.55. All variables together explained 21.4% of the variance in respiratory exchange ratio, with peak oxygen pulse being the most informative. CONCLUSION: Demographic, physical activity, and cardiopulmonary exercise test measures could not classify meeting peak exercise criteria (respiratory exchange ratio ≥ 1.1) at a satisfactory accuracy. Correlations between respiratory exchange ratio and oxygen pulse suggest the augmentation of stroke volume with exercise may affect the Fontan patient's ability to sustain high-intensity exercise.

Single ventricular strain measures correlate with peak oxygen consumption in children and adolescents with Fontan circulation.

INTRODUCTION: Children with a single ventricle post-Fontan palliation are at increased risk of poor outcomes with peak oxygen consumption acting as a surrogate outcome marker. The purpose of this study is to evaluate the relationship between peak oxygen consumption and echocardiographic measures of ventricular function and deformation, including ventricular global longitudinal strain and dyssynchrony, in children and adolescents following Fontan palliation. METHODS: Patients (age 8-21 years) with single ventricle post-Fontan palliation were prospectively recruited and participated in an echocardiogram, including views optimised for two-dimensional speckle tracking, and a cardiopulmonary exercise test on a cycle ergometer to maximal volitional fatigue. RESULTS: Thirty-eight patients (mean age 13.7 ± 2.3 years) post-Fontan palliation had either a single left ventricular (n = 20), single right ventricular (n = 14), or biventricular (n = 4) morphology. Peak oxygen consumption (24.9 ± 5.6 ml/kg/minute) was correlated with global longitudinal strain (r = -0.435, p = 0.007), a strain discoordination time to peak index (r = -0.48, p = 0.003), and the presence of an electro-mechanical dyssynchrony strain pattern (p = 0.008). On multivariate regression modelling, these three variables were associated with peak oxygen consumption independently of age and sex. The single right ventricular group had evidence of possible diastolic dysfunction by E/e' compared to the single left ventricular and biventricular groups (p = 0.001). CONCLUSIONS: Strain analysis measures are correlated with peak oxygen consumption in this cohort of children, adolescents, and young adults following Fontan palliation, suggesting that ventricular mechanics may influence the efficiency of the Fontan circulation.

The influence of somatic maturity on the relationship between the triglyceride/high-density lipoprotein ratio and vascular health in children and adolescents with dyslipidemia.

INTRODUCTION: Both the triglyceride to HDL cholesterol (TG/HDL) ratio and timing of pubertal maturation have been identified as independent contributors to the development of atherosclerosis. OBJECTIVE: The purpose of our study was to determine the relationship between the TG/HDL ratio and measures of vascular health in children and adolescents with dyslipidemia stratified by somatic maturity. We hypothesized that somatic maturity would have a significant interaction with TG/HDL ratio and vascular health. METHODS: This was a longitudinal analysis of 120 children and adolescents (age 8-14 years) with dyslipidemia recruited from a pediatric preventive cardiology clinic. At baseline and each follow-up visit, a non-fasting serum lipid panel was collected and vascular health (carotid artery intima--media thickness, pulse wave velocity, augmentation index) was assessed. Peak height velocity (PHV) was calculated at each visit, and participants were stratified into groups by maturity offset (pre-PHV, mid-PHV, post-PHV). A mixed model design permitted baseline and follow-up visits to be classified as discrete data points. RESULTS: Of the n = 235 data points (pre-PHV = 23%, mid-PHV = 19%, and post-PHV = 58%), we identified no significant interaction between TG/HDL ratio, maturity offset, and measures of vascular structure or function. There was also no significant relationship found between TG/HDL and maturity group. Within the mid-pubertal group, there was weak relationship found between TG/HDL and augmentation index. CONCLUSION: Despite the well-described relationship between early pubertal maturation and development of cardiovascular risk factors in adulthood, we found that vascular damage resulting from an elevated TG/HDL ratio is not independently associated with somatic maturity.

Development and Initial Validation of a Frailty Score for Pediatric Patients with Congenital and Acquired Heart Disease.

Frailty is a multi-dimensional clinical syndrome that is associated with increased morbidity and mortality and decreased quality of life. Children/adolescents with heart disease (HD) perform significantly worse for each frailty domain compared to non-HD peers. Our study aimed to create a composite frailty score (CFS) that can be applied to children/adolescents with HD and evaluate associations between the CFS and outcomes. Children and adolescents (n = 30) with HD (73% single ventricle, 20% heart failure, 7% pulmonary hypertension) were recruited from 2016 to 2017 (baseline). Five frailty domains were assessed at baseline using measures validated for pediatrics: (1) Slowness: 6-min walk test; (2) Weakness: handgrip strength; (3) Fatigue: PedsQL Multi-dimensional Fatigue Scale; (4) Body composition: triceps skinfold thickness; and (5) Physical activity questionnaire. Frailty points per domain (range = 0-5) were assigned based on z-scores or raw questionnaire scores and summed to produce a CFS (0 = least frail; 25 = most frail). Nonparametric bootstrapping was used to identify correlations between CFS and cross-sectional change in outcomes over 2.2 ± 0.2 years. The mean CFS was 12.5 ± 3.5. In cross-sectional analyses of baseline data, correlations (|r|≥ 0.30) were observed between CFS and NYHA class, the number of ancillary specialists, total prescribed medications, heart failure medications/day, exercise test derived chronotropic index and percent predicted VO2peak, and between child and parent proxy PEDsQL. At follow-up, CFS was correlated with an increase in the number of heart failure medications (r = 0.31). CFS was associated with cross-sectional outcomes in youth with heart disease. Longitudinal analyses were limited by small sample sizes due to loss to follow-up.

Practices and Procedures in Clinical Pediatric Exercise Laboratories in North America.

Interinstitutional differences in clinical pediatric exercise laboratory (CPEL) practices may affect patient care and efficacy of multicenter research. PURPOSE: To describe current practices/procedures in CPELs and explore differences in CPELs employing exercise physiologists to those that do not. METHODS: A 40-item survey was distributed to CPELs in North America focusing on (1) staffing; (2) exercise stress testing (EST) volumes, reporting, and interpretation; and (3) EST procedures/protocols. RESULTS: Of the 55 responses, 89% were in the United States, 85% were children's hospitals with university affiliation, and 58% were cardiology specific. Exercise physiologists were employed in 56% of CPELs, and 78% had master's degrees or higher. Certifications were required in most CPELs (92% emergency life-support, 27% professional, and 21% clinical). Median volume was 201 to 400 ESTs per year, 80% used treadmill, and 10% used cycle ergometer as primary modalities. Ninety-three percent of CPELs offered metabolic ESTs, 87% offered pulmonary function testing, 20% used institution-specific EST protocols, and 72% offered additional services such as cardiac/pulmonary rehabilitation. CPELS staffing exercise physiologists performed higher volumes of ESTs (P = .004), were more likely to perform metabolic ESTs (P = .028), participated in more research (P < .001), and provided services in addition to ESTs (P = .001). CONCLUSIONS: Heterogeneity in CPELs staffing and operation indicates need for standardization.

Heart Rate Recovery Following Exercise Testing in Pediatric Patients with Acyanotic Repaired Congenital Heart Disease.

Attenuated heart rate recovery (HRR) following peak exercise has been shown to be a predictor of mortality in populations of adults with Fontan palliation, coronary artery disease, heart failure, and heart transplantation. However, few have studied HRR in children and adolescents with congenital heart disease (CHD). This case-control study compared HRR patterns from exercise stress testing in children and adolescents with and without repaired acyanotic CHD (raCHD). Retrospective analysis included patients aged 10-18 years who had exercise testing between 2007 and 2017. The raCHD cohort included patients with Tetralogy of Fallot, transposition of the great arteries, coarctation, truncus arteriosus, atrioventricular septal defect, pulmonary outflow obstruction, aortic stenosis and/or insufficiency, or septal defects. Those in the control cohort were matched for age, sex, BMI, peak METs achieved, and peak heart rate (HR). HR at 1-min intervals throughout the 10-min recovery period and HRR patterns were analyzed. The study included n = 584 individuals (raCHD: n = 146), median age 14 years old, 67.1% male. The cohorts had similar resting and peak HRs. Linear mixed-effects models (LMM) suggested statistically significant cohort-by-time interaction for HR in exercise recovery, with the largest mean difference at minute-6 (2.9 bpm, p = 0.008). When comparing lesion types, LMM found no cohort or cohort-by-time interaction. While minute-6 of exercise recovery was statistically significant, the difference was 2.9 bpm and may not have clinical significance. These results suggest that HRR in pediatric raCHD patients should not vary from their healthy peers, and an attenuated HRR may not be directly attributed to underlying raCHD.

Weekly Frequency of Meeting the Physical Activity Guidelines and Cardiometabolic Health in Children and Adolescents.

PURPOSE: This study aimed to examine the association of the frequency component of the weekly PA guidelines on CmH in youth. METHODS: Cross-sectional accelerometer data from the 2003-2006 National Health and Nutrition Examination Survey included youth age 6-18 yr with ≥4 d, ≥10 h of wear time, and averaging ≥60 min·d-1 of MVPA (n = 656). Participants were categorized into quartiles based on the proportion of days where they met the guidelines (≥60 min of MVPA). CmH variables were categorized as weight status/body anthropometrics, blood pressure, cholesterol, and fasting serum laboratory results. Propensity score weighting was applied to quartiles, and general linear modeling was used to compare associations of quartiles with CmH variables. RESULTS: Results are displayed as percent of days meeting guidelines (DMG; 95% confidence interval): MVPA in minutes per week: Q1 (n = 156; DMG = 45.8% (43.4%-48.1%); MVPA 467.5, min·wk-1), Q2 (n = 165; DMG = 62.6% (61.6%-63.7%); MVPA, 474.4 min·wk-1), Q3 (n = 148; DMG = 75% (74.1%-75.8%); MVPA, 446.5 min·wk-1), Q4 (n = 187; DMG = 92.2% (87.7%-96.6%); MVPA, 453.2 min·wk-1). After adjusting for confounders and multiple comparisons, there were no clinically significant differences in weight status/body anthropometrics, blood pressure, cholesterol, or fasting serum laboratory results between DMG quartiles. CONCLUSIONS: We found no association between the proportion of DMG and CmH in children and adolescents. Our study suggests that achieving an overall weekly average of 60 min·d-1 of MVPA seems to be sufficient for CmH regardless of the 7 d·wk-1 frequency requirement of the PA guideline.

VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes.

Chronic non-healing wounds, frequently caused by diabetes, lead to lower quality of life, infection, and amputation. These wounds have limited treatment options. We have previously engineered growth factors to bind to exposed extracellular matrix (ECM) in the wound environment using the heparin-binding domain of placental growth factor-2 (PlGF-2123-144), which binds promiscuously to ECM proteins. Here, in the type 1 diabetic (T1D) NOD mouse model, engineered growth factors (eGFs) improved both re-epithelialization and granulation tissue formation. eGFs were even more potent in combination, and the "triple therapy" of vascular endothelial growth factor-A (VEGF-PlGF-2123-144), platelet-derived growth factor-BB (PDGF-BB-PlGF-2123-144), and heparin-binding epidermal growth factor (HB-EGF-PlGF-2123-144) both improved wound healing and remained at the site of administration for significantly longer than wild-type growth factors. In addition, we also found that changes in the cellular milieu of a wound, including changing amounts of M1 macrophages, M2 macrophages and effector T cells, are most predictive of wound-healing success in the NOD mouse model. These results suggest that the triple therapy of VEGF-PlGF-2123-144, PDGF-BB-PlGF-2123-144, and HB-EGF-PlGF-2123-144 may be an effective therapy for chronic non-healing wounds in that occur as a complication of diabetes.

Physical Activity Patterns in Children and Adolescents With Heart Disease.

PURPOSE: To quantify the differences in daily physical activity (PA) patterns, intensity-specific volumes, and PA bouts in youth with and without heart disease (HD). METHODS: Seven-day PA was measured on children/adolescents with HD (n = 34; median age 12.4 y; 61.8% male; 70.6% single ventricle, 17.7% heart failure, and 11.8% pulmonary hypertension) and controls without HD (n = 22; median age 12.3 y; 59.1% male). Mean counts per minute were classified as sedentary, light, and moderate to vigorous PA (MVPA), and bouts of MVPA were calculated. PA was calculated separately for each hour of wear time from 8:00 to 22:00. Multilevel linear mixed modeling compared the outcomes, stratifying by group, time of day, and day part (presented as median percentage of valid wear time [interquartile range]). RESULTS: Compared with the controls, the HD group had more light PA (33.9% [15%] vs 29.6% [9.5%]), less MVPA (1.7% [2.5%] vs 3.2% [3.3%]), and more sporadic bouts (97.4% [5.7%] vs 89.9% [9.2%]), but fewer short (2.0% [3.9%] vs 7.1% [5.7%]) and medium-to-long bouts (0.0% [1.9%] vs 1.6% [4.6%]) of MVPA. The HD group was less active in the late afternoon, between 15:00 and 17:00 (P < .03). There were no differences between groups in sedentary time. CONCLUSION: Children/adolescents with HD exhibit differences in intensity-specific volumes, PA bouts, and daily PA patterns compared with controls.

Treatment effects may remain the same even when trial participants differed from the target population.

OBJECTIVES: Randomized controlled trials (RCTs) have been criticized for lacking external validity. We assessed whether a trial in people with type I diabetes mellitus mirrored the wider population and applied sample-weighting methods to assess the impact of differences on our trial's findings. STUDY DESIGN AND SETTING: The Relative Effectiveness of Pumps over MDI and Structured Education trial was nested within a large UK cohort capturing demographic, clinical, and quality of life data for people with type I diabetes mellitus undergoing structured diabetes-specific education. We first assessed whether our RCT participants were comparable with this cohort using propensity score modeling. After this, we reweighted the trial population to better match the wider cohort and re-estimated the treatment effect. RESULTS: Trial participants differed from the cohort in regard to sex, weight, HbA1c, and also quality of life and satisfaction with current treatment. Nevertheless, the treatment effects derived from alternative model weightings were similar to that of the original RCT. CONCLUSION: Our RCT participants differed in composition to the wider population, but the original findings were unaffected by sampling adjustments. We encourage investigators take steps to address criticisms of generalizability but doing so is problematic; external data, even if available, may contain limited information and analyses can be susceptible to model misspecification.

Translation of the Frailty Paradigm from Older Adults to Children with Cardiac Disease.

Children and adolescents with cardiac disease (CCD) have significant morbidity and lower quality of life. However, there are no broadly applicable tools similar to the frailty score as described in the elderly, to define functional phenotype in terms of physical capability and psychosocial wellbeing in CCD. The purpose of this study is to investigate the domains of the frailty in CCD. We prospectively recruited CCD (8-17.5 years old, 70% single ventricle, 27% heart failure, 12% pulmonary hypertension; NYHA classes I, II and III) and age and gender matched healthy controls (total n = 56; CCD n = 34, controls n = 22; age 12.6 ± 2.6 years; 39.3% female). We measured the five domains of frailty: slowness, weakness, exhaustion, body composition and physical activity using developmentally appropriate methods. Age and gender-based population norms were used to obtain Z scores and percentiles for each measurement. Two-tailed t-tests were used to compare the two groups. The CCD group performed significantly worse in all five domains of frailty compared to healthy controls. Slowness: 6-min walk test with Z score -3.9 ± 1.3 vs -1.4 ± 1.3, p < 0.001; weakness: handgrip strength percentile 18.9 ± 20.9 vs 57.9 ± 26.0, p < 0.001; exhaustion: multidimensional fatigue scale percentile 63.7 ± 13.5 vs 83.3 ± 14.4, p < 0.001; body composition: height percentile 43.4 ± 29.5 vs 71.4 ± 25.2, p < 0.001, weight percentile 46.0 ± 36.0 vs 70.9 ± 24.3, p = 0.006, BMI percentile 48.4 ± 35.5 vs 66.9 ± 24.2, p = 0.04, triceps skinfold thickness 41.0 ± 24.0 vs 54.4 ± 22.1, p = 0.04; physical activity: pediatric activity questionnaire score 2 ± 0.6 vs 2.7 ± 0.6, p < 0.001. The domains of frailty can be quantified in children using developmentally appropriate methods. CCD differ significantly from controls in all five domains, supporting the concept of quantifying the domains of frailty. Larger longitudinal studies are needed to study frailty in CCD and examine if it predicts adverse health outcomes.Clinical Trial Registration: The ClinicalTrials.gov identification number is NCT02999438. https://clinicaltrials.gov/ct2/show/NCT02999438.

Proportion of Adults Meeting the 2018 Physical Activity Guidelines for Americans According to Accelerometers.

The new 2018 Physical Activity Guidelines for Americans provides updated recommendations for physical activity behavior. These guidelines remove the requirement for physical activity to be obtained in bouts of at least 10 min. The purpose of the present study was to provide an updated estimate of the proportion of adults meeting the physical activity guidelines, based on nationally representative data using accelerometers. Data from 6,525 adults were included in this study. The proportion of adults meeting the physical activity guidelines according to the Department of Health and Human Services and according to the American College of Sports Medicine were estimated using (a) lifestyle activities and (b) ambulatory activities only. Estimates of the proportion of adults meeting the physical activity guidelines ranged from 3.4 to 95.6%, even when based on the same data. The large range of these estimates suggest that challenges exist when using accelerometer data to estimate the levels of physical activity behavior in the population. Further, the large range indicates that, perhaps, physical activity guidelines should not be used as a reference point for behavior change. Instead, we suggest that efforts should be made to promote physical activity in reference to current behavior.

Handheld Indirect Calorimetry as a Clinical Tool for Measuring Resting Energy Expenditure in Children with and without Obesity.

Background: Resting energy expenditure (REE) is a valuable measure in clinical management of obesity and other chronic illnesses. Gold standard methods for measuring REE (e.g., Douglas bags and metabolic cart) are too expensive and cumbersome for an outpatient clinical setting. The purpose of this study was to determine the accuracy of a handheld indirect calorimeter (HHIC) and prediction equations (PEs) for measurement of REE in youth with and without obesity. Methods: Fifty-three children and adolescents (12.8 ± 4.3 years, 50.9% female) had REE measured first with a MedGem™ HHIC for 10 minutes, followed by a reference indirect calorimeter system (ParvoMedics TrueOne 2400™) with hood canopy and dilution pump for 30 minutes. REE was also estimated using nine PEs as follows: Henry-1, Henry-2, Schofield, World Health Organization, Molnar, Muller, Herrmann, Schmelzle, and Harris-Benedict. Concordance correlation coefficients and Bland-Altman analyses were used for comparisons among PEs, MedGem HHIC, and metabolic cart. Results: The observed correlation between the HHIC and the reference system was rc = 0.89 with a mean bias of 2.27 ± 3.41 kcal/(kg·d) (9.1% ± 14.7%). Regarding PE, Molnar had the highest agreement with the reference system [rc = 0.93, bias of 2.17 ± 2.04 kcal/(kg·d); 9.8% ± 8.1%], followed by Harris-Benedict (rc = 0.89; 13.8% ± 8.9%), Henry-2 (rc = 0.89; 15% ± 7.6%), and Henry-1 (rc = 0.86; 16.7% ± 7.3%). All PEs were less accurate for children with overweight/obesity. Conclusions: Compared to PE, the HHIC provided more accurate REE estimates for children across the age and BMI spectrum, although positive bias was present throughout. Difference in positive bias between the HHIC and the Molnar equation may be clinically significant for youth with overweight/obesity.

Modifiable Clinical Correlates of Vascular Health in Children and Adolescents with Dyslipidemia.

Atherosclerosis promoting cardiovascular disease risk factors (CVDrf) are highly prevalent among youth in the U.S. Determining which standard modifiable clinical measures (SMCMs) has the greatest impact on vascular structure and function is valuable for the health care provider to help identify children at highest risk. The aim of this study was to determine modifiable outpatient clinical predictors of vascular health in youth with CVDrf. Children and adolescents with CVDrf (n = 120, 13.1 ± 1.9 years, 49% female) were recruited from a pediatric preventive cardiology clinic. The SMCMs included BMI z-score, waist-to-height ratio (WTHR), lipid panel, hemoglobin A1c, blood pressure (BP), presence of tobacco smoke exposure, and presence of hypertriglyceridemic waist (HTW) phenotype (triglycerides ≥ 110 mg/dL and waist circumference ≥ 90 percentile). Vascular function and structure were measured with pulse wave velocity (PWV), central systolic BP (CSP), augmentation index (AIx), and carotid artery intima-media thickness (cIMT). Sex and height specific z-scores for PWV, CSP, and cIMT were used. Multiple linear regression with backwards selection identified SMCMs which strongly predicted vascular function and structure. Among SMCMs, WTHR and HTW were the most frequent predictors of vascular function (PWV: R2 = 0.32; CSP: R2 = 0.35; AIx R2 = 0.13). Other predictors of vascular function included hemoglobin A1C, BP, and BMI z-score. Systolic BP and LDL cholesterol were predictors of vascular structure (cIMT: R2 = 0.14). The strongest predictors of vascular health in youth with CVDrf were related to measures of central obesity. Targeting these SMCM in lieu of vascular testing in outpatient clinic setting may be practical to identify children and adolescents at greatest risk for CVD.