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Our goal was to describe changes in bladder health, defined as "a complete state of physical, mental, and social well-being related to bladder function that permits daily activities, adapts to short-term stressors, and allows optimal well-being," in women over time.We used data on 15 lower urinary tract symptoms (LUTS) and interference from urinary experiences assessed at the baseline and 5-year followup interviews of the BACH (Boston Area Community Health) Survey to estimate changes in bladder health over time in women. Associations between baseline and followup bladder health (defined as the maximum frequency of LUTS or interference at each time point) were calculated by ordinal logistic regression and generalized linear models.A total of 2,526 women provided complete information on bladder health at baseline and followup. Over the 5-year followup, 6.5% of women maintained optimal bladder health (no LUTS or interference), 33.6% developed worse bladder health (including 10.4% who transitioned from optimal to less than optimal health), 31.4% maintained their less than optimal bladder health status and 28.7% improved. Despite these changes, women with poorer bladder health at baseline were still more likely to have poorer bladder health 5 years later (eg multivariable-adjusted relative risk=3.27, 95% confidence interval: 2.49-4.29 for severe LUTS/interference at followup among those with severe LUTS/interference at baseline).Findings from our large secondary analysis of BACH Survey data suggest considerable variability in bladder health over time, and underscore the importance of bladder health promotion to prevent the initial onset and progression of poor bladder health in women.

Perinatal brain injury is a primary cause of cerebral palsy, a condition resulting in life-long motor impairment. Infancy is an important period of motor system development, including development of the corticospinal tract (CST), the primary pathway for cortical movement control. The interaction between perinatal stroke recovery, CST organization, and resultant motor outcome in infants is not well understood. Here, we present a protocol for multimodal longitudinal assessment of brain development and motor function following perinatal brain injury using transcranial magnetic stimulation and magnetic resonance imaging to non-invasively measure CST functional and structural integrity across multiple timepoints in infants 3 to 24 months of age. We will further assess the association between cortical excitability, integrity, and motor function. This protocol will identify bioindicators of motor outcome and neuroplasticity, and subsequently inform early detection, diagnosis, and intervention strategies for infants with perinatal stroke, brain bleeds and related diagnoses.

To describe the methods for the in-person musculoskeletal (MSK) assessment of the RISE FOR HEALTH (RISE) study, a population-based multicenter prospective cohort study designed to identify factors associated with bladder health (BH) conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS).A subset of RISE participants who express interest in the in-person assessment are screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete a standardized MSK assessment to evaluate core stability (four component core stability test, lumbar spine pain (seated slump test), pelvic girdle pain, (sacroiliac joint, anterior superior iliac spine, pubic symphysis tenderness, and pelvic girdle pain provocation test), hip pain (flexion, abduction, internal rotation and flexion, adduction and external rotation) and pelvic girdle function (active straight leg raise). Participants are also asked to complete the Short Physical Performance Battery to measure balance, gait speed, lower extremity strength, and functional capacity.Detailed online and in-person MSK training sessions led by physical therapy were used to certify research staff at each clinical center before the start of RISE in-person assessments. All evaluators exceeded the pre-specified pass rates.The RISE in-person MSK assessment will provide further insight into the role of general body MSK health and dysfunction and the spectrum of BH.

The spectrum of bladder health and the factors that promote bladder health and prevent lower urinary tract symptoms (LUTS) among women are not well understood. This manuscript describes the rationale, aims, study design, sampling strategy, and data collection for the RISE FOR HEALTH (RISE) study, a novel study of bladder health in women conducted by the Prevention of Lower Urinary Tract Symptom (PLUS) Research Consortium.RISE is a population-based, multicenter, prospective longitudinal cohort study of community-dwelling, English- and Spanish-speaking adult women based in the United States. Its goal is to inform the distribution of bladder health and the individual factors (biologic, behavioral, and psychosocial) and multilevel factors (interpersonal, institutional, community, and societal) that promote bladder health and/or prevent LUTS in women across the life course. Key study development activities included the: (1) development of a conceptual framework and philosophy to guide subsequent activities, (2) creation of a study design and sampling strategy, prioritizing diversity, equity, and inclusion, and (3) selection and development of data collection components. Community members and cross-cultural experts shaped and ensured the appropriateness of all study procedures and materials. RISE participants will be selected by simple random sampling of individuals identified by a marketing database who reside in the 50 counties surrounding nine PLUS clinical research centers. Participants will complete self-administered surveys at baseline (mailed paper or electronic) to capture bladder health and LUTS, knowledge about bladder health, and factors hypothesized to promote bladder health and prevent LUTS. A subset of participants will complete an in-person assessment to augment data with objective measures including urogenital microbiome specimens. Initial longitudinal follow-up is planned at 1 year.Findings from RISE will begin to build the necessary evidence base to support much-needed, new bladder health promotion and LUTS prevention interventions in women.

To describe the methods for the in-person assessment of the RISE FOR HEALTH (RISE) study, a population-based multicenter prospective cohort study designed to identify factors that promote bladder health and/or prevent lower urinary tract symptoms in adult women, conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS).A subset of RISE participants who express interest in the in-person assessment will be screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete 15 physical assessments in addition to height and weight, to assess pelvic floor muscle function, musculoskeletal (MSK) status, and pain, and to provide urogenital microbiome samples. Pelvic floor muscle assessments include presence of prolapse, strength, levator attachment integrity (tear) and myofascial pain. MSK tests evaluate core stability, lumbar spine, pelvic girdle and hip pain and function. Participants are asked to complete the Short Physical Performance Battery to measure balance, lower extremity strength, and functional capacity. All participants are asked to provide a voided urine sample and a vaginal swab for microbiome analyses; a subset of 100 are asked to contribute additional samples for feasibility and validation of a home collection of urinary, vaginal, and fecal biospecimens.Online and in-person training sessions were used to certify research staff at each clinical center before the start of RISE in-person assessments. Standardized protocols and data collection methods are employed uniformly across sites.The RISE in-person assessment is an integral portion of the overall population-based RISE study and represents an innovative approach to assessing factors hypothesized to promote bladder health and/or prevent lower urinary tract symptoms. Data collected from this assessment will be used to prioritize future research questions and prevention strategies and interventions. This description of the assessment methods is intended to provide methodologic transparency and inform other researchers who join efforts to understand and improve bladder health.

(s): Existing bladder-specific measures lack ability to assess a range of bladder health from poor to optimal health. We report evidence for validity of the self-administered, multidimensional Bladder Health Scales and Function Indices for research in adult women.A cross-sectional population-based validation study with random assignment to paper or electronic administration was conducted using national address-based probability sampling supplemented by purposive sampling of women with lower urinary tract symptoms surrounding 7 clinical research centers. Construct validity of the Bladder Health Scales and Function Indices was guided by Multitrait-Multimethod approach using health and condition-specific questionnaires, bladder diaries, expert ratings of bladder health, and noninvasive bladder function testing. Internal dimensional validity was evaluated using factor analysis; internal reliability was assessed using paired t-tests and 2-way mixed effects Intraclass Correlation Coefficient models. Mode comparisons used chi-square, Fisher Exact or t-tests. Convergent validity was evaluated using Pearson correlations with the external construct measures and known-group validity was established with comparison of women known and unknown to be symptomatic with urinary conditions.The sample included 1,072 participants. Factor analysis identified ten scales with Cronbach's alpha ranging 0.74-0.94. Intraclass correlation coefficients of scales ranged from 0.55-0.94. Convergent validity of ten scales and six indices ranged from 0.52- 0.83. Known-group validity was confirmed for all scales and indices. Item distribution was similar by mode of administration.The paper and electronic forms of the Bladder Health Scales and Function Indices are reliable and valid measures of bladder health for use in women's health research.

Measurements of liver volume from MR images can be valuable for both clinical and research applications. Automated methods using convolutional neural networks have been used successfully for this using a variety of different MR image types as input. In this work, we sought to determine which types of magnetic resonance images give the best performance when used to train convolutional neural networks for liver segmentation and volumetry. Abdominal MRI scans were performed at 3 Tesla on 42 adolescents with obesity. Scans included Dixon imaging (giving water, fat, and T2* images) and low-resolution T2-weighted scout images. Multiple convolutional neural network models using a 3D U-Net architecture were trained with different input images. Whole-liver manual segmentations were used for reference. Segmentation performance was measured using the Dice similarity coefficient (DSC) and 95% Hausdorff distance. Liver volume accuracy was evaluated using bias, precision, intraclass correlation coefficient, normalized root mean square error (NRMSE), and Bland-Altman analyses. The models trained using both water and fat images performed best, giving DSC = 0.94 and NRMSE = 4.2%. Models trained without the water image as input all performed worse, including in participants with elevated liver fat. Models using the T2-weighted scout images underperformed the Dixon-based models, but provided acceptable performance (DSC ≥ 0.92, NMRSE ≤ 6.6%) for use in longitudinal pediatric obesity interventions. The model using Dixon water and fat images as input gave the best performance, with results comparable to inter-reader variability and state-of-the-art methods.

Background: Toileting behaviors are increasingly recognized as factors potentially contributing to development of lower urinary tract symptoms (LUTS). Objectives: To examine adult women's toileting behaviors and LUTS across age and race/ethnicity groups and relationships between toileting behaviors and LUTS. Design: Planned secondary analysis of questionnaire data collected in a focus group study on bladder health. Settings: Questionnaires were completed at the conclusion of focus groups conducted in community settings affiliated with seven research centers across the United States. Participants: Community-living women regardless of LUTS status. Methods: Forty-four focus groups were conducted with 360 adolescent and adult cisgender women. After each focus group, participants completed questionnaires to assess toileting behaviors (Toileting Behaviors-Women's Elimination Behaviors Scale (TB-WEB)) and their experience of LUTS (Lower Urinary Tract Symptom Tool), This analysis includes quantitative data from the subgroup of 316 participants who completed the questionnaires. Results: Participants ranged in age from 18 to 93 years (Mean= 50.2 years). A significant effect for age was found for delayed voiding behavior, reported by 76.5% of women ages 18–25 years and 21.9% of those 75+ years (p

Goals The goal of this study was to evaluate whether proton pump inhibitor (PPI) use is cross-sectionally associated with hypomagnesemia and whether hypomagnesemia mediates the prospective association between PPIs and cardiovascular disease (CVD) risk. Background Use of PPIs has been associated with hypomagnesemia, primarily in case reports or within insurance databases. Both PPI use and low serum magnesium (Mg) have been associated with modestly higher CVD risk. Yet, the interrelation between PPI use and Mg in relation to CVD risk is unclear. Study The 4436 Atherosclerosis Risk in Communities participants without prevalent CVD at visit 5 (baseline, 2011-2013) were included. Multivariable relative risk regression was used for cross-sectional analyses between PPI and hypomagnesemia prevalence (≤0.75 mmol/L). Incident CVD (defined by atrial fibrillation, coronary heart disease, CVD mortality, heart failure, stroke) was identified through 2017. Multivariable Cox regression was used to examine the PPI-CVD association. Results Participants were mean±SD aged 75±5 years; 63% were women, 23% Black, and 24% were PPI users. PPI users had 1.24-fold (95% confidence interval: 1.08-1.44) higher prevalence of hypomagnesemia than nonusers. Over a median 5 years of follow-up, 684 incident CVD events occurred. PPI users had higher CVD risk [hazard ratio (95% confidence interval) 1.31 (1.10-1.57)] than nonusers. The effect estimate was largely unchanged when hypomagnesemia was added to the model as a potential mediator. Conclusions In this elderly community-based study, PPI users had a higher prevalence of hypomagnesemia than in nonusers. PPI users also had higher CVD risk than nonusers; however, it appears unlikely that hypomagnesemia explains associations of PPIs with CVD risk.

Background: Little research to date has investigated the spectrum of bladder health in women, including both bladder function and well-being. Therefore, we expanded our previous baseline analysis of bladder health in the Boston Area Community Health (BACH) Survey to incorporate several additional measures of bladder-related well-being collected at the 5-year follow-up interview, including one developed specifically for women. Methods: At follow-up, participants reported their frequency of 15 lower urinary tract symptoms (LUTS), degree of life impact from and thought related to urinary symptoms or pelvic/bladder pain/discomfort, and perception of their bladder condition. Prevalence ratios were calculated by generalized linear models with robust variance estimation, adjusting for LUTS risk factors and individual LUTS. The BACH Survey was approved by the New England Research Institutes Institutional Review Board and all participants provided written informed consent. Results: Generally similar findings were observed in the 5-year cross-sectional analysis as at baseline, irrespective of how we categorized LUTS or measured bladder-related well-being. Approximately one in five women (16.2%–18.0% of 2527 eligible women) reported no LUTS and no diminished bladder-related well-being, the majority (55.8%–65.7%) reported some LUTS and/or diminished well-being, and a further one in five (16.9%–26.6%) reported the maximum frequency, number, or degree of LUTS and/or diminished well-being. Measures of storage function (urinating again after

When conducting a meta-analysis involving prevalence data for an outcome with several subtypes, each of them is typically analyzed separately using a univariate meta-analysis model. Recently, multivariate meta-analysis models have been shown to correspond to a decrease in bias and variance for multiple correlated outcomes compared to univariate meta-analysis, when some studies only report a subset of the outcomes. In this article, we propose a novel Bayesian multivariate random effects model to account for the natural constraint that the prevalence of any given subtype cannot be larger than that of the overall prevalence. Extensive simulation studies show that this new model can reduce bias and variance when estimating subtype prevalences in the presence of missing data, compared to standard univariate and multivariate random effects models. The data from a rapid review on occupation and lower urinary tract symptoms by the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium are analyzed as a case study to estimate the prevalence of urinary incontinence and several incontinence subtypes among women in suspected high risk work environments.

Author(s): Schmitz, Kathryn H; Bavendam, Tamara; Brady, Sonya S; Brubaker, Linda; Burgio, Kathryn; Harlow, Bernard L; James, Aimee; Lukacz, Emily S; Miller, Janis M; Newman, Diane K; Palmer, Mary H; Rudser, Kyle; Sutcliffe, Siobhan; Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium | Abstract: AimsPrior research on lower urinary tract symptoms (LUTS) has focused on the treatment and management of these conditions with scant attention to prevention. The Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium was formed to address the complexities of preventing LUTS and promoting bladder health.MethodsHerein, we describe challenges faced and strategies used to develop the PLUS Research Consortium into an engaged and productive transdisciplinary scientific team. We apply four previously defined team science phases (development, conceptualization, implementation, and translation) to frame our progress.ResultsStrategies to progress through the development phase included the generation of a shared mission, and valuing of other disciplinary perspectives. The conceptualization phase included generating a shared language and developing a team transdisciplinary orientation. During the implementation phase, the group developed roles and procedures and focused on conflict management. The translation phase includes continued refinement of the mission and goals, implementation of research protocols, and robust dissemination of the scientific work products related to bladder health.ConclusionA diverse group has matured into a productive transdisciplinary team science consortium. Achieving this outcome required dedicated effort for each member to engage in activities that often required more time than single discipline research activities. Provision of the necessary time and tools has fostered a transdisciplinary team science culture and rich research agenda that reflects the complexity of the health issue to be addressed. Our experience may be useful for others embarking on team science projects.

BACKGROUND: A physical symptom score (PSS) for the mucopolysaccharidosis (MPS) disorders has been developed to quantitate the somatic burden of disease across multiple organ systems. Studies have demonstrated the sensitivity and its relationship to age, IQ and adaptive functioning of the PSS in older children. With the onset of newborn screening, there is an increased need to characterize the somatic symptoms in the earliest stages of life, especially for young children under 36 months of age. Consequently, a new scale, Infant Physical Symptom Score (IPSS), was developed to score physical symptoms in infants and toddlers. OBJECTIVE: PART I. To create a measure to quantify somatic burden in patients with MPS disorders under 36 months of age. The IPSS assess outcomes and changes in somatic disease in individuals with MPS disorders diagnosed very early in life. PART II. To determine the relationship between IPSS and other measures to evaluate its validity and utility, a) we evaluated the relationship between the IPSS and PSS in the same patients with MPS I over time to determine if the two scales are measuring the same concepts, and b) we evaluated the association between IPSS and a functional adaptive measure over time with a focus on the age at first treatment (under 36 months) to determine if the IPSS has predictive value. METHODS: PART I. The Infant Physical Symptom Score (IPSS) for the infant population in MPS disorders was established using data from 39 patients enrolled in the Lysosomal Disease Network longitudinal MPS I study (U54NS065768). All of these patients had Hurler syndrome (MPS IH) and underwent hematopoietic stem cell transplant (HSCT) at the University of Minnesota. Items for the IPSS were selected by reviewing CRFs prepared for the MPS I longitudinal study and examining medical records of these patients prior to HSCT based on the knowledge gained from the development of the PSS. PART II. Of those 39 patients, a subset of 19 were all seen 9 to 12 years post HSCT. Having retrospectively calculated their IPSS prior to HSCT, we categorized them by age at HSCT, and examined their most recent PSS along with Composite and Daily Living Skills scores on the Vineland Adaptive Behavior Scales – Second Edition (VABS-II). RESULTS AND CONCLUSION: The total score on the IPSS collected prior to transplant differed by patient’s age at transplant, as expected in this progressive condition. Those transplanted at ≤12 months of age had a mean score of 7.4, which was significantly lower, suggesting less somatic disease burden, compared to those transplanted at >12 to ≤24 months (mean 11.8) and >24 to ≤36 months (mean 13.6). Higher IPSS reflects more evidence of somatic disease burden and lower IPSS reflects less evidence of disease burden. Nine to 12 years later, the severity level as measured by the PSS was comparable to severity on the IPSS suggesting that the two scales are measuring similar concepts. Retrospectively calculated pre-transplant IPSS were negatively associated with higher VABS-II Composite scores 9–12 years later (p value-0.015) and to a lesser extent Daily Living Skills scores (p value-0.081). We conclude that the IPSS appears to be a useful approach to quantifying the somatic disease burden of MPS IH patients under 36 months of age.

Background: Healthcare disparities associated with race/ethnicity and low English proficiency are well established in the US. We sought to determine if there are race/ethnic differences in anti-obesity medication prescription rates among youth with severe obesity (body mass index (BMI) ≥1.2 times the 95th percentile and/or BMI ≥35 kg/m2) treated in a pediatric weight management clinic (PWMC). We secondarily sought to determine if, among youth from families in whom English was not the primary language, there are differences in prescription rates between those using an interpreter during visits and those not. Methods: We reviewed electronic health records of youth 2–18 years old with severe obesity seen at a PWMC from 2012–2020. Race/ethnicity was self-reported and categorized as Non-Hispanic White (NHW), Hispanic/Latino, Non-Hispanic Black (NHB), Asian, American Indian/Alaska Native and Mixed. Anti-obesity medicines included stimulants (i.e. phentermine, lisdexamfetamine), topiramate, naltrexone (± bupropion), and glucagon-like peptide-1 agonists. We used Poisson regression models with robust standard errors to compare incidence rates of medicine prescription (incidence rate ratio (IRR), accounting for visit frequency) within the first 1 and 3 years of being followed in a PWMC. We controlled for age, baseline degree of obesity (percent of the 95th BMI percentile (%BMIp95)), number of obesity-related comorbidities (i.e. insulin resistance, hypertension, fatty liver), area-level socioeconomic status (median household income based on ZIP code), and interpreter use. We repeated similar analyses among families in whom English was not the primary language, comparing those using an interpreter with those not. Results: From 2012–2020, 1258 youth (mean age 11.8 years; %BMIp95 143%) were seen in our PWMC (57% NHW, 19% Hispanic/Latino, 16% NHB) of which 26% were prescribed anti-obesity medication. 86% primarily spoke English and 5.2% used an interpreter. There were no statistically significant differences in the IRR of prescriptions by race/ethnicity at 1 and 3 years; however, although not statistically significant point estimates suggest Hispanic/Latino youth being prescribed medication less often at 1 (IRR 0.71; p=0.08) and 3 (IRR 0.75; p=0.13) years compared to NHW. Among non-primary English speakers, rates of prescriptions were higher at 1 (IRR 5.7; p Conclusions: We found no significant race/ethnic differences in anti-obesity medication prescriptions; however, Hispanic/Latino youth received fewer prescriptions, albeit not statistically significant. Among non-primary English speakers, use of an interpreter was associated with increased prescriptions. Our results suggest that addressing healthcare disparities and language barriers may improve care delivery for youth with obesity.

Authorship and dissemination policies vary across NIH research consortia. Our purpose was to describe elements of real-life policies in use by eligible U01 clinical research consortia. Principal investigators of eligible, active U01 clinical research projects identified in the NIH Research Portfolio Online Reporting Tools database were asked to share relevant policies. The characteristics of key policy elements, determined a priori, were reviewed and quantified, when appropriate. Eighty-one research projects met search criteria and 21 groups provided policies which were examined for key elements (e.g., in quotations): “manuscript proposals reviewed and approved by committee” (90%); “guidelines for acknowledgements” (86%); “formation of the writing team” (71%); “process for final manuscript review and approval” (71%), “responsibilities for lead author” (67%), “guidelines for other types of publications” (67%); “draft manuscript review and approval” (62%); “recommendation for number of members per consortium site” (57%); and “requirement to identify individual contributions in the manuscript” (19%). Authorship/dissemination policies for large team science research projects are highly variable. Creation of an NIH policies repository and accompanying toolkit with model language and recommended key elements could improve comprehensiveness, ethical integrity, and efficiency in team science work while reducing burden and cost on newly funded consortia and directing time and resources to scientific endeavors.

Measurements of liver volume from MR images can be valuable for both clinical and research applications. Automated methods using convolutional neural networks have been used successfully for this using a variety of different MR image types as input. In this work, we sought to determine which types of magnetic resonance images give the best performance when used to train convolutional neural networks for liver segmentation and volumetry.Abdominal MRI scans were performed at 3 Tesla on 42 adolescents with obesity. Scans included Dixon imaging (giving water, fat, and T2* images) and low-resolution T2-weighted anatomical scans. Multiple convolutional neural network models using a 3D U-Net architecture were trained with different input images. Whole-liver manual segmentations were used for reference. Segmentation performance was measured using the Dice similarity coefficient (DSC) and 95% Hausdorff distance. Liver volume accuracy was evaluated using bias, precision, and normalized root mean square error (NRMSE).The models trained using both water and fat images performed best, giving DSC = 0.94 and NRMSE = 4.2%. Models trained without the water image as input all performed worse, including in participants with elevated liver fat. Models using the T2-weighted anatomical images underperformed the Dixon-based models, but provided acceptable performance (DSC ≥ 0.92, NMRSE ≤ 6.6%) for use in longitudinal pediatric obesity interventions. The model using Dixon water and fat images as input gave the best performance, with results comparable to inter-reader variability and state-of-the-art methods.

BACKGROUND: There are limited data comparing the relative associations of various BMI metrics with adiposity and cardiometabolic risk factors in youth. OBJECTIVE: Examine correlations of 7 different BMI metrics with adiposity, cardiometabolic risk factors, and biomarkers (i.e. blood pressure, waist circumference, cholesterol, leptin, insulin, high molecular weight adiponectin, high-sensitivity c-reactive protein (hsCRP)). METHODS: This was a cross-sectional analysis of youth in all BMI categories. BMI metrics: BMI z-score (BMIz), extended BMIz (ext. BMIz), BMI percentile (BMIp), percent of the BMI 95th percentile (%BMI(p95)), percent of the BMI median (%BMI(p50)), triponderal mass index (TMI), and BMI (BMI). Correlations between these BMI metrics and adiposity, visceral adiposity, cardiometabolic risk factors and biomarkers were summarized using Pearson’s correlations. RESULTS: Data from 371 children and adolescents ages 8–21 years old were included in our analysis: 52% were female; 20.2% with Class I obesity, 20.5% with Class II, and 14.3% with Class III obesity. BMIp consistently demonstrated lower correlations with adiposity, risk factors, and biomarkers (r = 0.190–0.768) than other BMI metrics. The %BMI(p95) and %BMI(p50) were marginally more strongly correlated with measures of adiposity as compared to other BMI metrics. The ext.BMIz did not meaningfully outperform BMIz. CONCLUSION: Out of all the BMI metrics evaluated, %BMI(p95) and %BMI(p50) were the most strongly correlated with measures of adiposity. %BMI(p95) has the benefit of being used currently to define obesity and severe obesity in both clinical and research settings. BMIp consistently had the lowest correlations. Future research should evaluate the longitudinal stability of various BMI metrics and their relative associations with medium to long-term changes in adiposity and cardiometabolic outcomes in the context of intervention trials.

Aim: We assessed reproducibility of endothelial microparticles (EMPs) enumeration among youth. Methods & results: Four microparticle (MP) indices – total MP per microliter platelet free plasma (PFP), total EMPs per microliter PFP, percent activated EMPs and percent lactadherin positive (LACT[+]) of total EMPs – were measured at two visits (baseline and 7 ± 3 days follow-up) to determine reproducibility overall and by obesity status. We examined CD31+ or CD144+ with CD41-EMP events of size 0.3–1.0 μm. No statistically significant differences were observed between visits for any of the four MP indices. The within-participant and between-participant coefficient of variation was acceptable (range: 1.13–2.37) with good intraclass-correlation coefficient for all indices except total MP per microliter (range: 0.10–1.00). Conclusion: Total EMPs per microliter PFP, percent-activated EMPs and percent LACT(+) of total EMPs are reproducible among youth.

Purpose: Many adult survivors of childhood cancer are at high-risk of developing cardiovascular disease. Cancer therapy may cause damage to the vascular endothelium, thereby initiating atherosclero...

ObjectivePrevious research suggests attention and white matter (WM) abnormalities in individuals with mucopolysaccharidosis type I (MPS I); this cross-sectional comparison is one of the first to examine the relationship of WM structural abnormalities as measured by corpus callosum (CC) volumes with attention scores to evaluate this relationship in a larger sample of patients with MPS I.MethodsVolumetric MRI data and performance on a computerized measure of sustained attention were compared for 18 participants with the severe form of MPS I (MPS IH), 18 participants with the attenuated form of MPS I (MPS IATT), and 60 typically developing age-matched controls.ResultsThe MPS I groups showed below-average mean attention scores (p < 0.001) and smaller CC volumes (p < 0.001) than controls. No significant associations were found between attention performance and CC volume for controls. Attention was associated with posterior CC volumes in the participants with MPS IH (p = 0.053) and total (p = 0.007) and anterior (p < 0.001) CC volumes in participants with MPS IATT.ConclusionsWe found that attention and CC volumes were reduced in participants with MPS I compared to typically developing controls. Smaller CC volumes in participants with MPS I were associated with decreased attention; such an association was not seen in controls. While hematopoietic cell transplantation used to treat MPS IH may compound these effects, attention difficulties were also seen in the MPS IATT group, suggesting that disease effects contribute substantially to the clinical attentional difficulties seen in this population.

Background: Alpha-1-antitrypsin (A1AT) deficiency (A1ATD) is characterized by accelerated degradation of lung function. We examined our experience with lung transplantation for chronic obstructive pulmonary disease (COPD) with and without A1ATD to compare survival and rates of postoperative surgical complications. Methods: Patients with A1ATD and non-A1ATD COPD undergoing lung transplantation from 1988−2015 at our institution were analyzed. Complications were categorized into non-gastroenteritis gastrointestinal (GI), wound, airway, and reoperation for bleeding. Overall and complication-free survival were evaluated using Kaplan-Meier curves and Cox proportional hazards models. Results: Three hundred and eighty-five patients underwent lung transplant for COPD (98 A1ATD). For A1ATD, 56.1% underwent single lung transplantation (80.6% for COPD). Early overall and complication-free survival was worse for A1ATD, but this trend reversed at longer follow up. Unadjusted estimated survival showed advantage for COPD at 90 days and 1 year, which attenuated by 5 years and reversed at 10 years (P

Purpose Recruitment for pediatric non-invasive brain stimulation (NIBS) studies is often challenged by low enrollment. Understanding parental perceptions regarding NIBS is crucial to develop new communication strategies to increase enrollment. Design/methodology/approach Integrating a crossed-disciplinary approach, the authors conducted a survey at the 2018 Minnesota State Fair querying the perception of risk and preferences of current and future parents associated with pediatric NIBS research. The survey consisted of 28 closed-text questions including demographics, photographs portraying NIBS, terminologies and factors related to NIBS studies. Findings Complete surveys were analyzed from 622 parent participants. A significant number of participants (42.8%) perceived the photographs of NIBS as “risky.” Additionally, 65.43% perceived the term “Non-invasive brain therapy” as not risky, a word combination not currently being used when recruiting potential participants. Over 90% (561/622) of participants chose the photograph of child-friendly MRI suite. Research limitations/implications Although this survey identified aspects crucial in recruitment for pediatric NIBS research, there were limitations. For example, the authors did not record the sex or demographic distribution (e.g. rural versus urban setting) of the participants. These factors may also influence recruitment messaging. Originality/value For important medical research to impact and improve the lives of the potential remedies, participation by the public in clinical trials is necessary. Often the general public perceives the trials as risky as a result of poor marketing communication recruitment material. This study sought to be understood if how the message is encoded has an impact on the decoding by the receiver.

Background: Studies examining the association between hedonic hunger, that is, having frequent thoughts about food in the absence of an energy deficit, and obesity in youth show mixed results. This may be due to the confounding effect of binge eating, which has been associated with both hedonic hunger and obesity. The purpose of this study was to determine the extent to which hedonic hunger is associated with obesity independent of binge eating in youth. Methods: Data for this cross-sectional study were collected from youth enrolled in a larger study of cardiovascular disease and obesity. Linear regression models were used to assess the association between hedonic hunger measured by Power of Food Scale (PFS) and binge eating measured by Eating Disorder Examination-Questionnaire, on percent of the 95th BMI percentile (BMIp95). Results: Among 269 participants (mean age 12.8 years), 16.4% endorsed binge eating. PFS was positively associated with BMIp95 with a difference in percent of BMIp95 of 5.9% [95% confidence interval (1.5–10.3), p = 0.009]. However, when binge eating was added to the model, the relationship between PFS and BMIp95 was no longer significant. Conclusion: Hedonic hunger, above and beyond binge eating, may not be associated with BMI. Future research should examine whether screening for and targeting binge eating rather than hedonic hunger in weight management care may have more impact on obesity outcomes. Clinical Trial Registration number: NCT01508598.

Introduction: Endothelial activation represents one of the earliest signs of the atherosclerotic process. Microparticles (MPs) in plasma, particularly endothelial MPs (EMPs) are reproducible biomarkers of endothelial dysfunction with a simple blood draw. The goal of this study was to examine the association of obesity with MPs, EMPs (CD31+/CD41– and/or CD 144+/CD31–), and activated EMPs (CD106+). Hypothesis: We hypothesized that higher body mass index (BMI), body fat percent (BF%), and visceral adipose tissue (VAT) would be associated with higher levels of MPs, EMPs, and activated EMPs. Methods: This was a cross-sectional study of 280 children and adolescents ages 8-18 years old. Whole venous blood was collected and processed for platelet free-plasma (PFP) collection less than 3 hours after being drawn. PFP samples were prepared using serial centrifugations and then frozen as 100 μl aliquots at -80 ° C. MPs were measured using flow cytometry with size ranging from 0.3 to 1.0 μm. EMPs were defined as MP with CD31+/CD41– and/or CD 144+/CD31–. Active EMP was identified as EMP with CD 106+. BF% and VAT were measured using dual X-ray absorptiometry. Linear (total MPs and EMPs) and logistic (activated EMPs) regression models were used to examine the associations with adiposity group, BF%, and VAT, adjusting for Tanner stage, sex, and race. Results: The mean age of the cohort was 12.7 years, consisting of 147 females and BMI distribution: 112 normal-weight, 77 overweight/obesity, 91 severe obesity. Youth with overweight/obesity and severe obesity had higher numbers of total MPs (28,690 per μL PFP/g [-2,315, 59,695], p=0.07 and 52,744 per μL PFP/g [22,163, 83,324], p85 th percentile compared to youth with a BMI th percentile. In the entire cohort, BF% (odds ratio, 1.02 [1.00, 1.04], p=0.108) and VAT (odds ratio, 1.00 [1.00, 1.00], p=0.472) were not significantly associated with active EMPs. Conclusions: Higher levels of endothelial cell damage and activation were associated with obesity and excess adiposity in youth. The potential role of MPs and EMPs as useful biomarkers of cardiovascular disease risk merits further study.

Summary Background Weight loss in children and adolescents with type 2 diabetes (T2D) is associated with improved glycaemic control. Objectives To assess the effects of liraglutide vs placebo on body mass index (BMI) and weight parameters in children and adolescents with T2D using data from the ellipse trial (NCT01541215). Methods The ellipse trial randomized participants (10‐85th percentile, T2D, glycated haemoglobin [HbA1c] 7.0%‐11.0% [if diet‐ and exercise‐treated] or 6.5% to 11.0% [if treated with metformin, basal insulin or both]) to liraglutide or placebo. This post‐hoc analysis evaluated changes from baseline to weeks 26 and 52 in absolute BMI, percent change in BMI and other weight‐related parameters. Changes were assessed by liraglutide overall (all doses) and liraglutide by dose (0.6, 1.2 and 1.8 mg/day) vs placebo using a pattern mixture model of observed data, with missing observations imputed from each treatment group. Results In total, 134 participants were included. There were statistically significant differences between groups in certain parameters, including absolute BMI (estimated treatment difference [ETD] –0.89 kg/m2; 95% confidence interval [CI] –1.71,–0.06) and percent change in BMI (ETD –2.73%; 95% CI –5.15,–0.30) at week 52, but none at week 26. Dose‐dependent effects were not observed for liraglutide vs placebo for all BMI/weight parameters. Conclusions Compared with placebo, liraglutide was associated with statistically significant reductions in BMI/weight parameters at week 52, but not week 26, in children and adolescents with T2D.

Background Bladder health is an understudied state and difficult to measure due to lack of valid and reliable instruments. While condition specific questionnaires assess presence, severity and degree of bother from lower urinary tract symptoms, the absence of symptoms is insufficient to assume bladder health. This study describes the methodology used to validate a novel bladder health instrument to measure the spectrum of bladder health from very healthy to very unhealthy in population based and clinical research. Methods Three samples of women are being recruited: a sample from a nationally representative general population and two locally recruited clinical center samples—women with a targeted range of symptom severity and type, and a postpartum group. The general population sample includes 694 women, 18 years or older, randomly selected from a US Postal delivery sequence file. Participants are randomly assigned to electronic or paper versions of the bladder health instrument along with a battery of criterion questionnaires and a demographic survey; followed by a retest or a two-day voiding symptom diary. A total of 354 women around 7 clinical centers are being recruited across a spectrum of self-reported symptoms and randomized to mode of completion. They complete the two-day voiding symptom diary as well as a one-day frequency volume diary prior to an in-person evaluation with a standardized cough stress test, non-invasive urine flowmetry, chemical urine analysis and post void residual measurement. Independent judge ratings of bladder health are obtained by interview with a qualified health care provider. A total of 154 postpartum women recruited around 6 of the centers are completing similar assessments within 6–12 weeks postpartum. Dimensional validity will be evaluated using factor analysis and principal components analysis with varimax rotation, and internal consistency with Cronbach’s alpha. Criterion validity will be assessed using multitrait-multimethod matrix including correlations across multiple data sources and multiple types of measures. Discussion We aim to validate a bladder health instrument to measure the degree of bladder health within the general population and among women (including postpartum) recruited from local clinical centers. Trial registration NCT04016298 Posted July 11, 2019 (https://www.clinicaltrials.gov/ct2/show/NCT04016298?cond=bladder+health&draw=2&rank=1).

Background Circulating endothelial cells (CECs) reflect early changes in endothelial health; however, the degree to which CEC number and activation is related to adiposity and cardiovascular risk factors in youth is not well described. Methods and Results Youth in this study (N=271; aged 8–20 years) were classified into normal weight (body mass index [BMI] percentage P >0.05). Youth with severe obesity had a higher degree of CEC activation compared with normal weight youth (8.3%; 95% CI, 1.1–15.6 [ P =0.024]). Higher CEC number was associated with greater body fat percentage (0.02 per percentage; 95% CI, 0.00–0.03 [ P =0.020]) and systolic blood pressure percentile (0.01 per percentage; 95% CI, 0.00–0.01 [ P =0.035]). Higher degree of CEC activation was associated with greater visceral adipose tissue (5.7% per kg; 95% CI, 0.4–10.9 [ P =0.034]) and non–high‐density lipoprotein cholesterol (0.11% per mg/dL; 95% CI, 0.01–0.21 [ P =0.039]). Conclusions Methods of CEC quantification are associated with adiposity and cardiometabolic risk factors and may potentially reflect accelerated atherosclerosis as early as childhood.

PurposeWe describe the item development and cognitive evaluation process used in creating the Prevention of Lower Urinary Tract Symptoms Bladder Health Instrument (PLUS-BHI).Materials and methodsQuestions assessing bladder health were developed using reviews of published items, expert opinion, and focus groups' transcript review. Candidate items were tested through cognitive interviews with community-dwelling women and an online panel survey. Items were assessed for comprehension, language, and response categories and modified iteratively to create the PLUS-BHI.ResultsExisting measures of bladder function (storage, emptying, sensation components) and bladder health impact required modification of time frame and response categories to capture a full range of bladder health. Of the women 167 (18-80 years old) completed individual interviews and 791 women (18-88 years) completed the online panel survey. The term "bladder health" was unfamiliar for most and was conceptualized primarily as absence of severe urinary symptoms, infection, or cancer. Coping mechanisms and self-management strategies were central to bladder health perceptions. The inclusion of prompts and response categories that captured infrequent symptoms increased endorsement of symptoms across bladder function components.ConclusionsBladder health measurement is challenged by a lack of awareness of normal function, use of self-management strategies to mitigate impact on activities, and a common tendency to overlook infrequent lower urinary tract symptoms. The PLUS-BHI is designed to characterize the full spectrum of bladder health in women and will be validated for research use.

Summary Background Lower urinary tract symptoms (LUTS) are common in children and adolescents. Non-invasive tests evaluating bladder function are generally preferred over invasive tests, yet few studies have explored the range of normative values for these tests in healthy, asymptomatic children. Objective To define normative reference ranges for non-invasive tests of bladder function in healthy, asymptomatic girls and adolescents. Study design A comprehensive search strategy was performed in seven electronic databases through October 2019. English-language studies reporting data on voiding frequency, voided and postvoid residual volumes (PVR) and uroflowmetry results in healthy, asymptomatic girls (mean age ≥ 5 years) were included. Two independent reviewers performed study review, data extraction, and quality assessment. Overall mean estimates and 95% confidence intervals for each bladder function parameter were calculated using random effects models, and 95% normative reference values were estimated. Results Ten studies met eligibility criteria for the meta-analysis (n = 2143 girls, age range: 3–18). Mean estimates of maximum voided volume and PVR were 233.4 ml (95% CI 204.3–262.6; n = 1 study) and 8.6 ml (95% CI 4.8–12.4; n = 2 studies) respectively. Pooled mean estimates for uroflowmetry parameters were: 21.5 ml/s (95% CI 20.5–2.5) for maximum flow rate (n = 6 studies), 12.5 ml/s (95% CI 11.2–13.8) for mean flow rate (n = 6 studies), 6.8 s (95% CI 4.4–9.3) for time to maximum flow (n = 3 studies), 15.7 s (95% CI 13.0–18.5) for flow time (n = 3 studies), and 198.7 ml (95% CI 154.2–234.2) for voided volume (n = 9 studies). No studies reported estimates of voiding frequency. Between-study heterogeneity was high (89.0–99.6%). Conclusions Although we were able to calculate pooled mean estimates for several parameters, the small number of included studies and the wide age ranges of participants preclude generalization of reference values to all healthy girls. Further research is needed to determine normative reference values within specific age groups.

INTRODUCTION: Low serum magnesium (Mg) is associated with an increased incidence of atrial and ventricular arrhythmias. A richer phenotyping of arrhythmia indices, such as burden or frequency, may provide etiologic insights. OBJECTIVES: To evaluate cross-sectional associations of serum Mg with burden of atrial arrhythmias [atrial fibrillation (AF), premature atrial contractions (PAC), supraventricular tachycardia (SVT)], and ventricular arrhythmias [premature ventricular contractions (PVC), non-sustained ventricular tachycardia (NSVT)] over 2-weeks of ECG monitoring. METHODS: We included 2,513 ARIC Study visit 6 (2016-2017) participants who wore the Zio XT Patch—a leadless, ambulatory ECG-monitor—for up to 2-weeks. Serum Mg was modeled categorically and continuously. AF burden was categorized as intermittent or continuous based on the percent of analyzable time spent in AF. Other arrhythmia burdens were defined by the average number of abnormal beats per day. Linear regression was used for continuous outcomes; logistic and multinomial regression were used for categorical outcomes. RESULTS: Participants were mean±SD age 79±5 years, 58% were women and 25% black. Mean serum Mg was 0.82±0.08 mmol/F and 19% had hypomagnesemia (

(1) Background: Magnesium supplementation may be effective for the prevention of cardiometabolic diseases, but the mechanisms are unclear. Proteomic approaches can assist in identifying the underlying mechanisms. (2) Methods: We collected repeated blood samples from 52 individuals enrolled in a double-blind trial which randomized participants 1:1 to oral magnesium supplementation (400 mg magnesium/day in the form of magnesium oxide) or a matching placebo for 10 weeks. Plasma levels of 91 proteins were measured at baseline with follow-up samples using the Olink Cardiovascular Disease III proximity extension assay panel and were modeled as arbitrary units in a log2 scale. We evaluated the effect of oral magnesium supplementation for changes in protein levels and the baseline association between serum magnesium and protein levels. The Holm procedure was used to adjust for multiple comparisons. (3) Results: Participants were 73% women, 94% white, and had a mean age of 62. Changes in proteins did not significantly differ between the two intervention groups after correction for multiple comparisons. The most statistically significant effects were on myoglobin [difference &minus, 0.319 log2 units, 95% confidence interval (CI) (&minus, 0.550, &minus, 0.088), p = 0.008], tartrate-resistant acid phosphatase type 5 (&minus, 0.187, (&minus, 0.328, &minus, 0.045), p = 0.011), tumor necrosis factor ligand superfamily member 13B (&minus, 0.181, (&minus, 0.332, &minus, 0.031), p = 0.019), ST2 protein (&minus, 0.198, (&minus, 0.363, &minus, 0.032), p = 0.020), and interleukin-1 receptor type 1 (&minus, 0.144, (&minus, 0.273, &minus, 0.015), p = 0.029). Similarly, none of the associations of baseline serum magnesium with protein levels were significant after correction for multiple comparisons. (4) Conclusions: Although we did not identify statistically significant effects of oral magnesium supplementation in this relatively small study, this study demonstrates the value of proteomic approaches for the investigation of mechanisms underlying the beneficial effects of magnesium supplementation. Clinical Trials Registration: ClinicalTrials.gov NCT02837328.

Background The normal rate of subclinical vascular aging from adolescence to young adulthood has not been well‐characterized. We conducted a 5‐year longitudinal study among adolescents with normal‐weight, obesity, and/or type 2 diabetes mellitus to examine trajectories of early vascular aging. Methods and Results Adolescents (mean [SD] age 17.6 [3.5]; 35.3% male) had either normal weight (n=141), obesity (n=156), or type 2 diabetes mellitus (n=151) at baseline. Primary metrics used for early vascular aging included measures of vascular structure (carotid intima‐media thickness [cIMT]; common, internal, and bulb) and arterial stiffness (carotid‐femoral pulse wave velocity, and augmentation index). Longitudinal (5‐year) outcomes were examined using generalized estimating equations adjusting for baseline value, sex, race, and age. Compared with participants with normal weight, those with obesity had greater positive change in common cIMT (0.05 mm [0.03, 0.06]; P P =0.033), internal cIMT (0.03 mm [0.01, 0.05]; P P =0.001), and those with type 2 diabetes mellitus had greater positive change in common cIMT (0.05 mm [0.04, 0.07]; P P P P P P P =0.01), internal cIMT (0.008 mm [0.003, 0.013]; P =0.001), and pulse wave velocity carotid‐femoral (0.066 m/sec [0.002, 0.130]; P =0.042). Conclusions These longitudinal data support the hypothesis that the presence of obesity, type 2 diabetes mellitus, and elevated baseline systolic blood pressure in early life accelerates the progression of risk factors key in the development of early vascular aging.

Introduction: Apolipoproteins are key regulators of cholesterol transport and clearance with each apolipoprotein having a specific protective or atherogenic role. The relationship between subclinical cardiovascular risk and each of the apolipoproteins in the pediatric population is insufficiently described within the literature. Therefore, the purpose of this study was to examine the association of apolipoproteins with measures of vascular structure and function in pediatric population. Hypothesis: We hypothesized apolipoprotein AI, AII, and CII would demonstrate a positive association, and apolipoprotein B, B/AI ratio, CIII, CIII/CII ratio, and E a negative association with carotid intima-media thickness (cIMT) and carotid-radial pulse wave velocity (PWV). Methods: A cross-sectional study of 338 children and adolescents (160 males, 178 females) aged 8-21 years (mean age 13.0±2.8 years) with a range of adiposities from normal body weight to severe obesity (mean BMI 26.8±8.9 kg/m 2 ). Apolipoproteins (AI, AII, B, CII, CIII, and E) were measured via human apolipoprotein magnetic bead panel (Millipore, MA, USA). Ultrasound imaging of the carotid artery was used to measure cIMT. PWV, a measure of arterial stiffness, was assessed via applanation tonometry (SphygmoCor TM ). Total body fat percent (BF%) was measured using dual X-ray absorptiometry. Linear regression models were adjusted for Tanner stage, sex, and race with further adjustments for BF%. Data are presented as mean [95% CI] with Holms-adjusted p-values to account for multiple testing. All apolipoprotein ratios were scaled to 0.1 μg/mL. Methods: There were significant positive associations between PWV and apolipoproteins: AII (0.036 m/sec per 10 μg/mL [0.017, 0.056], p = 0.010), E (0.158 m/sec per 10 μg/mL [0.08, 0.235], p = 0.002), and CIII/CII ratio (0.033 [0.014, 0.052], p = 0.019). After adding BF% to the models, PWV remained positively associated with higher levels of apolipoproteins: AII (0.036 m/sec per 10 μg/mL [0.016, 0.055], p = 0.012), E (0.161 m/sec per 10 μg/mL [0.082, 0.239], p = 0.002), and CIII/CII ratio (0.033 [0.014, 0.052], p = 0.02). Before accounting for multiple testing, apolipoprotein CIII/CII ratio was positively associated with cIMT (0.001 [0, 0.003], p = 0.033), but failed to maintain significance after p-value correction. Otherwise, there were no significant associations between any apolipoprotein and cIMT in the presence or absence of BF%. Conclusions: These findings suggest higher levels of apolipoprotein AII, E, and CIII/CII ratio are associated with higher arterial stiffness (PWV) in pediatrics, both in the presence and absence of excess body fat. Apolipoproteins, specifically AII, E, and CIII/CII ratio, may exert their effects on vascular function (PWV) before altering vascular structure (cIMT), which is congruent with the chronological pathophysiology of atherosclerosis.

Background Cardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities. Methods Prospective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals and P-values. Results Morquio A patients demonstrated significantly higher (P P P = 0.003) than control subjects and other MPS patients. Aortic root dilatation was noted in 56% of the Morquio A cohort, which also had highly prevalent mitral (73%) and aortic (82%) valve thickening, though hemodynamically significant valve dysfunction was less frequent (9%). Conclusions Increased carotid elasticity in Morquio A patients is an unexpected contrast to the reduced elasticity observed in other MPS. These Morquio A cIMT findings corroborate MPS IVA arterial post-mortem reports and are consistent with cIMT of other MPS. Aortic root dilatation in Morquio A indicates arterial elastin dysfunction, but their carotid hyperelasticity indicates other vascular intima/media components, such as proteoglycans, may also influence artery function. Studying MPS I and IVA model systems may uniquely illuminate the function of glycosaminoglycan-bearing proteoglycans in arterial health.

Background:This is a cross-sectional study aiming to understand the early characteristics and background of bone health impairment in clinically well children with Fontan circulation.Methods:We enrolled 10 clinically well children with Fontan palliation (operated >5 years before study entrance, Tanner stage ≤3, age 12.1 ± 1.77 years, 7 males) and 11 healthy controls (age 12.0 ± 1.45 years, 9 males) at two children’s hospitals. All patients underwent peripheral quantitative CT. For the Fontan group, we obtained clinical characteristics, NYHA class, cardiac index by MRI, dual x-ray absorptiometry, and biochemical studies. Linear regression was used to compare radius and tibia peripheral quantitative CT measures between Fontan patients and controls.Results:All Fontan patients were clinically well (NYHA class 1 or 2, cardiac index 4.85 ± 1.51 L/min/m2) and without significant comorbidities. Adjusted trabecular bone mineral density, cortical thickness, and bone strength index at the radius were significantly decreased in Fontan patients compared to controls with mean differences −30.13 mg/cm3 (p = 0.041), −0.31 mm (p = 0.043), and −6.65 mg2/mm4 (p = 0.036), respectively. No differences were found for tibial measures. In Fontan patients, the mean height-adjusted lumbar bone mineral density and total body less head z scores were −0.46 ± 1.1 and −0.63 ± 1.1, respectively, which are below the average, but within normal range for age and sex.Conclusions:In a clinically well Fontan cohort, we found significant bone deficits by peripheral quantitative CT in the radius but not the tibia, suggesting non-weight-bearing bones may be more vulnerable to the unique haemodynamics of the Fontan circulation.

We investigated the safety, feasibility, and efficacy of transcranial direct current stimulation (tDCS) combined with constraint-induced movement therapy (CIMT) in children and young adults with unilateral cerebral palsy. Twenty participants were randomized to receive active or sham tDCS. The intervention consisted of 10 consecutive weekday sessions of tDCS applied to the non-lesioned hemisphere (20 min) concurrently with CIMT (120 min). Participants, caregivers, and interventionists were blinded to group assignment. The primary safety outcome investigated adverse events. The primary behavioral outcome was the Assisting Hand Assessment. All 20 participants (mean age = 12.7 yrs, range = 7.4–21.6 years) were evaluated for the primary outcomes. No serious adverse events occurred, and the most commonly reported minor adverse events were headache and itchiness. Both groups demonstrated a significant improvement in hand function after the intervention, although no significant effect of tDCS was observed (between-group difference = −2.18, 95% CI = [−6.48, 2.12], p = 0.30). Although hand function improved overall, no significant differences between intervention groups were found. Children with preserved corticospinal tract circuitry from the lesioned hemisphere, compared to those without, showed greater improvement in hand function (mean difference = 3.04, 95% CI = [−0.64, 6.72], p = 0.099). Our study demonstrates the safety and feasibility of serial sessions of tDCS, and presents preliminary evidence for the effect of CST circuitry on outcomes following tDCS/CIMT. Future work in children with unilateral cerebral palsy should focus on the optimal dosing and consider individual brain circuitry when describing response to combined interventions. Clinical Trials Registration Clinicaltrials.gov NCT 02250092 .