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INTRODUCTION/AIMS Glucocorticoid-induced osteoporosis with vertebral fractures is frequent in patients with Duchenne muscular dystrophy (DMD). In this study, we evaluated the effects of oral bisphosphonate (BP) therapy on the prevalence and severity of vertebral fractures by vertebral morphometry assessment. METHODS We reviewed the records and radiographs of patients with DMD who had been treated with oral BP (weekly alendronate) and had undergone routine spine radiographic monitoring for glucocorticoid-induced osteoporosis at Cincinnati Children's Hospital Medical Center between 2010 and 2017. Study outcomes were thoracic and lumbar vertebral fracture prevalence and severity, assessed by Genant semiquantitative grading of vertebral morphometry, for up to 5 years of treatment. RESULTS Fifty-two patients (median age, 11.8 years; 88% prepubertal; 31% nonambulatory) had been treated with long-term glucocorticoids (median duration, 4.7 years at BP start). Most patients (75%) had mild vertebral height loss or fractures (Genant grade = 0 or 1) at baseline. The prevalence of vertebral fractures at each year of treatment was not statistically different from that at baseline (P = .08-1.00). Serial radiographs showed no longitudinal change in severity by Genant grade in most vertebrae (64%-80%). Improvement in vertebral fracture grade was observed in some patients. DISCUSSION We observed stable prevalence of vertebral fractures and no change in severity by Genant grade in most vertebrae for up to 5 years of treatment. Oral BP may mitigate development or progression of vertebral fractures and be beneficial for secondary prevention of glucocorticoid-induced osteoporosis in this population.

Objectives Physical examinations to characterize pubertal maturation may be unacceptable for children enrolled in research studies. Studies confirm the utility of pubertal self staging for research, but there has been limited comparison of self examination with hormone biomarkers. Our objective was to assess concordance of pubertal self staging with hormone biomarkers of puberty. Methods Participants were enrolled in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort study. At age 12 years, 139 females and 112 males completed pubertal self staging including breast and pubic hair development in females and pubic hair development in males. No clinical physical examination was performed. Hormone concentrations were measured in 102 females and 96 males including serum dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in all; estradiol in females; and testosterone in males. Results Estradiol was significantly associated with female breast stage, even when adjusted for BMI, with geometric least squares means (95%CI) of 13.2 (8.7, 20.2), 38.3 (29.9, 49.1), 59.4 (39.8, 88.6), and 81.2 (45.6, 144) pg/mL for breast stage 1–2, 3, 4, and 5, respectively. Testosterone was significantly associated with male pubic hair stage, with adjusted geometric least squares means (95%CI) of 37.6 (19.9, 71.1), 43.4 (27.7, 68.3), 126 (78.4, 203), 275 (146, 521), and 559 (237, 1319) ng/dL for pubic hair stage 1, 2, 3, 4, and 5, respectively. Conclusions Self assessed pubertal development was positively associated with hormonal biomarkers of puberty.

Purpose: The ‘5-2-1-0’ guidelines recommend that children: eat ≥5 servings of fruits/vegetables (‘5’), have ≤2 hours of screen-time (‘2’), have ≥1 hour of activity (‘1’), and drink 0 sugar-sweetened beverages (‘0’) daily. The pediatric emergency department (PED) treats children at risk for obesity and tobacco smoke exposure (TSE). We examined body mass index (BMI), overweight, obesity, TSE, and ‘5-2-1-0’ rates in children with TSE in the PED. Design: Cross-sectional study of PED children. Setting: The PED of a children’s hospital. Sample: Children with TSE >6 months-5 years old (N = 401). Measures: Sociodemographics, ‘5-2-1-0’ behaviors, BMI, and cotinine-confirmed TSE. Analysis: Associations between ‘5-2-1-0’ and sociodemographics were examined with logistic regression. Results: Mean (SD) age = 2.4 (1.6) years; 53.1% were Black; 65.8% had low-income; and 93.4% had TSE. Of 2-5-year-olds, mean (SD) BMI percentile was 66.2 (30.1), 16.1% were overweight and 20.6% were obese. In total, 10.5% attained ‘5’, 72.6% attained ‘2’, 57.8% of 2-5-year-olds attained ‘1’, and 9.8% attained ‘0’. Compared to White children, “other” race children were more likely to meet ‘5’ (aOR(95% CI):4.67(1.41, 5.45)); 2-5-years-olds (aOR(95%CI):0.60(0.38, 0.95)) and Black children (aOR(95%CI):0.36(0.21, 0.60)) were at decreased odds to meet ‘2’ compared to younger or White children, respectively. Compared to younger children, 2-5-year-olds were at decreased odds to meet ‘0’ (aOR(95%CI):0.08(0.02, 0.26)). Conclusion: Racially diverse, low-income children with TSE had low ‘5-2-1-0’ attainment. Interventions are needed to improve lifestyle habits in this population.

INTRODUCTION: We sought to determine the feasibility and validity of estimating post-stroke outcomes using information available in the electronic medical record (EMR) through comparison with outcomes obtained from telephone interviews. METHODS: The Greater Cincinnati Northern Kentucky Stroke Study is a retrospective population-based epidemiology study that ascertains hospitalized strokes in the study region. As a sub-study, we identified all ischemic stroke patients who presented to a system of 4 hospitals during the study period 1/1/2015–12/31/2015 and were discharged alive. Enrolled subjects (or proxies for cognitively-disabled patients) were contacted by telephone at 3 and 6 months post-stroke to determine current place of residence and two functional outcomes—the modified Rankin Score (mRS) and the EuroQol (EQ-5D). Concurrently, the lead study coordinator, blinded to the telephone assessment outcomes, reviewed all available EMRs to estimate outcome status. Agreement between outcomes estimated from the EMR with “gold-standard” data obtained from telephone interviews was analyzed using the kappa statistic or interclass correlation (ICC), as appropriate. For each outcome, EMR-determined results were evaluated for added value beyond the information readily available from the stroke hospital stay. RESULTS: Of 381 ischemic strokes identified, 294 (median [IQR] age 70 [60–79] years, 4% black, 52% female) were interviewed post-stroke. Agreement between EMR and telephone for 3-month residence was very good (kappa=0.84, 95% CI 0.74–0.94), good for mRS (weighted kappa=0.75, 95% CI 0.70–0.80), and good for EQ-5D (ICC=0.74, 95% CI 0.68–0.79). Similar results were observed at 6 months post stroke. At both 3 and 6 months post stroke, EMR-determined outcomes added value in predicting the gold standard telephone results beyond the information available from the stroke hospitalization; the added fraction of new information ranged from 0.25 to 0.59. CONCLUSIONS: Determining place of residence, mRS, and EQ-5D outcomes derived from information recorded in the EMR post-stroke, without patient contact, is feasible and has good agreement with data obtained from direct contact. However, we note that the level of agreement for mRS and EQ-5D was higher for proxy interviews and that the EMR often reflects health care providers’ judgments that tend to overestimate disability and underestimate quality of life.

There is an ongoing need to determine best practices for effective transition from pediatric to adult care for adolescents and emerging adults (EAs) with type 1 diabetes given the potential for poor health outcomes post-transfer. This study evaluated self-reported confidence ratings as measured by the Readiness of Emerging Adults with Diabetes Diagnosed in Youth (READDY) tool among adolescents and EAs with type 1 diabetes and the association of the confidence ratings with clinical and demographic characteristics, as well as provider documentation of relevant anticipatory guidance topics. The READDY is a diabetes-specific tool used to collect patient-reported confidence in transition preparation topics to target educational interventions. These interventions are divided into four domains: Diabetes Knowledge, Health System Navigation, Insulin Self-Management, and Health Behaviors. A retrospective chart review was conducted of patients 15–24 years of age with type 1 diabetes who completed the READDY survey between January 2017 and January 2018 at a single center. Overall patient-reported confidence levels were high. However, adolescents and EAs endorsed their lowest levels of confidence on items assessing knowledge of alcohol, tobacco, sexual health, and the impact of diabetes on pregnancy (females only), with the percentages of low scores of 20.7, 25.9, 35.9, and 42.9%, respectively. Documentation of provider counseling about screening and prevention of diabetes comorbidities, alcohol use, and tobacco use was associated with scores in the higher range for the corresponding item in the READDY survey. These findings highlight an opportunity to create interventions related to developmentally important topics for adolescents and EAs with type 1 diabetes to enhance successful transition preparation.

Osteoporosis is a major concern in patients with Duchenne muscular dystrophy. In this novel study of teriparatide treatment in 6 patients with severe osteoporosis, bone health (fractures, vertebral morphometry, and DXA) remained stable, with no adverse events. These findings will help inform future osteoporosis research in this challenging population. Despite standard therapy with vitamin D and bisphosphonates (BP), many patients with Duchenne muscular dystrophy (DMD) continue to sustain fragility fractures due to long-term glucocorticoid treatment and limited mobility. We aimed to evaluate the safety and efficacy of teriparatide for the treatment of severe osteoporosis in adolescent and young adult patients with DMD. We prospectively treated 6 patients with DMD who had severe osteoporosis with teriparatide 20 mcg subcutaneously daily for 1–2 years. Inclusion criteria were long-term glucocorticoid therapy, and severe osteoporosis despite treatment with BP, or intolerance to BP. We examined long bone and vertebral fracture outcomes, including vertebral morphometry measures, bone mineral density and content, bone formation markers, safety indices, and adverse events. The mean age at teriparatide start was 17.9 years (range 13.9–22.1 years). All 6 patients were on daily glucocorticoids (mean ± SD; duration 10.9 ± 2.5 years) and 5 were non-ambulatory. Five patients had been treated with BP for 7.9 ± 4.2 years. All had vertebral and a history of long bone fragility fractures at baseline. Vertebral heights and Genant fracture grading remained stable. Long bone fracture rate appeared to decrease (from 0.84/year to 0.09/year); one patient sustained a long bone fracture at 6 months of treatment. Trajectories for change in bone mineral density and content were not different post- vs. pre-teriparatide. Procollagen type 1 amino-terminal propeptide (P1NP) increased, while laboratory safety indices remained stable and non-concerning. No adverse events were observed. In six patients with DMD treated with teriparatide for severe osteoporosis, we observed stable bone health and modest increases in P1NP, without safety concerns. Further studies are needed to better understand teriparatide efficacy for treatment of osteoporosis in patients with DMD.

BACKGROUND: Adolescent obesity is associated with significant comorbidities including decreased quality of life (QOL). QOL improves after metabolic and bariatric surgery (MBS), but recent studies have demonstrated that certain gastrointestinal symptoms (GIS) worsen after surgery, including reflux symptoms, nausea, bloating and diarrhea. OBJECTIVE: The aim of this study was to evaluate QOL and the effect of these symptoms on QOL after bariatric surgery. SETTING: Five academic centers performing adolescent MBS in the United States. METHODS: We prospectively studied 228 adolescents undergoing MBS using the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. Gastrointestinal symptoms and QOL scores were assessed before surgery, at 6-months and yearly to 5 years after surgery. Analysis involved linear models examining QOL and the association between GIS and QOL adjusting for a priori determined covariates. RESULTS: Adjusting for body mass index (BMI) change over time, the physical component score (PCS) of the Short Form-36 (SF-36) increased after surgery from 44.2 at baseline to 54.4 at 5 years (p

The rising trend of obesity in the United States has been a growing concern within the healthcare system for decades. Since the early 1960s, the prevalence of obesity has more than doubled among U.S. adults, and one out of every three Americans is now considered obese according to the National Health and Nutrition Examination Survey [1,2]. Significant medical comorbidities have been associated with obesity and increased Body Mass Index (BMI); these include hypertension, dyslipidemia, coronary artery disease, stroke, sleep apnea, type II diabetes mellitus and certain types of cancer.

Metabolic syndrome (MetS) affects ∼10% of adolescents and is associated with cardiometabolic disease risk. The most prevalent MetS component is abdominal obesity. Healthy diet and physical activity (PA) are inversely associated with abdominal obesity and may reduce MetS risk in youth. Our aim was to examine associations of diet, activity, and abdominal obesity with MetS z-score (MetS-z).An analysis of National Health and Nutrition Examination Survey (NHANES) 2011-2016 data in adolescents was performed. Healthy Eating Index (HEI)- 2015 scores were calculated for diet quality, PA habits were used to determine alignment with national guidelines, and abdominal obesity was assessed by sagittal abdominal diameter (SAD). MetS-z represented severity or potential risk for MetS. Multivariable regression evaluated the relationships of HEI, SAD and PA with MetS-z. Among 1214 black and white adolescents, SAD was significantly associated with MetS-z [β (95% CI) = 0.17 (0.16, 0.19); P0.0001] while HEI-2015 components showed associations with MetS-z overall (HEI total, dairy, and sodium scores), and by sex (total, refined grains, dairy for males; added sugar, protein, whole grains for females). Mean HEI-2015 score was 47.4/100 (51.6 using the population-ratio method), and the proportion of adolescents meeting national PA guidelines was 37.6%, yet PA was not a significant predictor of MetS-z.US adolescents have poor diet quality and fewer than half meet PA guidelines. Strategies for preventing MetS and related conditions in adolescence should focus on weight management - specifically, abdominal fat reduction - with individualized diet counseling.

Background Stroke results in neurologic impairments and aerobic deconditioning that contribute to limited walking capacity which is a major barrier post-stroke. Current exercise recommendations and stroke rehabilitation guidelines recommend moderate-intensity aerobic training post-stroke. Locomotor high-intensity interval training is a promising new strategy that has shown significantly greater improvements in aerobic fitness and motor performance than moderate-intensity aerobic training in other populations. However, the relative benefits and risks of high-intensity interval training and moderate-intensity aerobic training remain poorly understood following stroke. In this study, we hypothesize that locomotor high-intensity interval training will result in greater improvements in walking capacity than moderate-intensity aerobic training. Methods Using a single-blind, 3-site randomized controlled trial, 50 chronic (> 6 months) stroke survivors are randomly assigned to complete 36 locomotor training sessions of either high-intensity interval training or moderate-intensity aerobic training. Main eligibility criteria are age 40–80 years, single stroke for which the participant received treatment (experienced 6 months to 5 years prior to consent), walking speed ≤ 1.0 m/s, able to walk at least 3 min on the treadmill at ≥ 0.13 m/s (0.3 mph), stable cardiovascular condition (American Heart Association class B), and the ability to walk 10 m overground without continuous physical assistance. The primary outcome (walking capacity) and secondary outcomes (self-selected and fast gait speed, aerobic fitness, and fatigue) are assessed prior to initiating training and after 4 weeks, 8 weeks, and 12 weeks of training. Discussion This study will provide fundamental new knowledge to inform the selection of intensity and duration dosing parameters for gait recovery and optimization of aerobic training interventions in chronic stroke. Data needed to justify and design a subsequent definitive trial will also be obtained. Thus, the results of this study will inform future stroke rehabilitation guidelines on how to optimally improve walking capacity following stroke. Trial registration ClinicalTrials.govNCT03760016. Registered on November 30, 2018.

Objectives Population-level estimates of the median intracerebral hemorrhage (ICH) volume would allow for the evaluation of clinical trial external validity and determination of temporal trends. We previously reported the median ICH volume in 1988. However, differences in risk factor management, neuroimaging, and demographics may have affected ICH volumes. The goal of this study is to determine the median volume of ICH within a population-based cross-sectional study, including whether it has changed over time. Methods The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was a population-based study of ICH among residents of the Greater Cincinnati/Northern Kentucky region from 2008 through 2012. This study utilizes those data and compares with ICH cases from the same region in 1988. Initial computed tomography images of the head were reviewed, and ICH volumes were calculated using consistent methodology. Results From 2008 through 2012, we identified 1117 cases of ICH. The median volume of ICH was 14.0 mL and was lower in black (11.6) than in white (15.5) patients. Median volumes of lobar and deep ICH were 28.8 mL and 9.8 mL, respectively. Median ICH volume changed significantly from 1988 to 2008–2012, with age-and-race-adjusted volume decreasing from 18.3 mL to 13.76 mL (p = 0.025). Conclusions Median volume of ICH was 13.76 mL, and this should be considered in clinical trial design. Median ICH volume has apparently decreased from 1988 to 2008–2012.

Background Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are effective for weight loss in adolescents with severe obesity. However, little is known about adverse gastrointestinal symptoms (GIS) following these operations in adolescents. The objective was to examine GIS over 5 years after surgery and differences by surgery type. Methods We prospectively studied 228 adolescents (161 RYGB, 67 VSG) undergoing bariatric surgery. Gastrointestinal symptoms were assessed before surgery, at 6-months, and yearly to 5 years after surgery. Symptom severity was dichotomized for analysis. Analysis of post-surgery symptoms involved linear models adjusting for baseline symptoms, BMI, early post-operative complication, sex, and race. Results Participants at surgery were 17 ± 1.6 years with preoperative BMI 53 ± 9.4 kg/m2. From 6 months to 5 years, gastroesophageal reflux symptoms (GERS), nausea, bloating, and diarrhea increased. Crude prevalence rates of GERS increased from 4% (1% RYGB, 11% VSG) at 6-months post-surgery to 14% (10% RYGB, 26% VSG) at 5-years. In adjusted analyses, the VSG group experienced 4-fold (4.85 95% CI 2.63, 8.91, p Conclusions Adolescents who underwent VSG experienced greater risk of GERS compared to those undergoing RYGB. Adolescents undergoing VSG should be counseled preoperatively about GERS and objectively monitored postoperatively for gastroesophageal reflux when indicated. Clinical trial registration ClinicalTrials.gov , Identifier: NCT00474318 , https://clinicaltrials.gov/ct2/show/NCT00474318?term=Teen-LABS&rank=1 . Type of Study Treatment Study. Level of Evidence Level II.

Aerobic exercise may acutely prime the brain to be more responsive to rehabilitation, thus facilitating neurologic recovery from conditions like stroke. This aerobic priming effect could occur through multiple mechanisms, including upregulation of circulating brain-derived neurotrophic factor (BDNF), increased corticospinal excitability, and decreased intracortical inhibition. However, optimal exercise parameters for targeting these mechanisms are poorly understood. This study tested the effects of exercise intensity on acute BDNF and neurophysiological responses. Sixteen ambulatory persons >6 mo poststroke performed three different 20-min exercise protocols in random order, approximately 1 wk apart, including the following: 1) treadmill high-intensity interval training (HIT-treadmill); 2) seated-stepper HIT (HIT-stepper); and 3) treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum BDNF and transcranial magnetic stimulation measures of paretic lower limb excitability and inhibition were assessed at multiple time points during each session. Compared with MCT-treadmill, HIT-treadmill elicited significantly greater acute increases in circulating BDNF and corticospinal excitability. HIT-stepper initially showed BDNF responses similar to HIT-treadmill but was no longer significantly different from MCT-treadmill after decreasing the intensity in reaction to two hypotensive events. Additional regression analyses showed that an intensity sufficient to accumulate blood lactate appeared to be important for eliciting BDNF responses, that the interval training approach may have facilitated the corticospinal excitability increases, and that the circulating BDNF response was (negatively) related to intracortical inhibition. These findings further elucidate neurologic mechanisms of aerobic exercise and inform selection of optimal exercise-dosing parameters for enhancing acute neurologic effects. NEW & NOTEWORTHY Acute exercise-related increases in circulating BDNF and corticospinal excitability are thought to prime the brain for learning. Our data suggest that these responses can be obtained among persons with stroke using short-interval treadmill high-intensity interval training, that a vigorous aerobic intensity sufficient to generate lactate accumulation is needed to increase BDNF, that interval training facilitates increases in paretic quadriceps corticospinal excitability, and that greater BDNF response is associated with lesser intracortical inhibition response.

Objectives The aim of this study was to assess associations between loss of control (LOC) eating and health outcomes among adolescents undergoing metabolic and bariatric surgery. Methods A total of 234 adolescents were studied before and up to 6 years after surgery in a prospective, observational cohort design. Adolescents provided self-reports of LOC eating, pain severity, sleep quality, polycystic ovary syndrome, gastroesophageal reflux disease, and medication usage and objective measures of fasting glucose, serum insulin, glycohemoglobin A1c , cholesterol, triglycerides, and blood pressure. χ2 tests, Wilcoxon rank sums, and generalized linear mixed models were used to assess concurrent and prospective associations between LOC eating and health indicators. Results LOC eating presented in 32.5% of adolescents before surgery and was positively associated with sleep disturbances and psychiatric medication usage. After surgery, LOC eating presented in 7.9% to 14.6% of participants and was correlated with improved low- and high-density lipoprotein cholesterol levels and greater back pain. LOC eating was inversely associated with low-density lipoprotein cholesterol at the next consecutive time point. Conclusions LOC eating was unexpectedly associated with improved low- and high-density lipoprotein cholesterol in adolescents undergoing metabolic and bariatric surgery. Deleterious effects of LOC eating on obesity-related health conditions, aside from back pain, were not detected. Metabolic and other weight-independent health benefits of surgery may persist postoperatively despite LOC eating and associated weight regain.

Exposure to maternal diabetes in utero increases the risk in the offspring for a range of metabolic disturbances. However, the timing and variability of in utero hyperglycemic exposure necessary to cause impairment have not been elucidated. The TEAM Study was initiated to evaluate young adult offspring of mothers with pregestational diabetes mellitus. This paper outlines the unique enrollment challenges of the TEAM Study and preliminary analysis of the association between exposure to diabetes in pregnancy and adverse metabolic outcomes. The TEAM Study enrolls offspring of women who participated in a Diabetes in Pregnancy (DiP) Program Project Grant between 1978 and 1995. The DiP Study collected medical and obstetric data across pregnancy. The first 96 eligible offspring of women with pregestational diabetes were age-, sex-, and race-matched to adults from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 with an OGTT. Descriptive and regression analyses were employed to compare TEAM participants to NHANES participants. Among a subset of TEAM participants, we compared the metabolic outcomes across maternal glucose profiles using a longitudinal data clustering technique that characterizes level and variability, in maternal glucose across pregnancy. By comparing categories of BMI, TEAM Study participants had over 2.0 times the odds of being obese compared to matched NHANES participants (for class III obesity, OR = 2.81 ; 95% confidence interval (CI): 1.15, 6.87). Increasing levels of two-hour glucose were also associated with in utero exposure to pregestational diabetes in matched analyses. Exposure to pregestational diabetes in utero may be associated with an increased risk of metabolic impairment in the offspring with clinical implications.

Introduction: To identify phenotypes of type 1 diabetes based on glucose curves from continuous glucose-monitoring (CGM) using functional data (FD) analysis to account for longitudinal glucose patterns. We present a reliable prediction model that can accurately predict glycemic levels based on past data collected from the CGM sensor and real-time risk of hypo-/hyperglycemic for individuals with type 1 diabetes. Methods: A longitudinal cohort study of 443 type 1 diabetes patients with CGM data from a completed trial. The FD analysis approach, sparse functional principal components (FPCs) analysis was used to identify phenotypes of type 1 diabetes glycemic variation. We employed a nonstationary stochastic linear mixed-effects model (LME) that accommodates between-patient and within-patient heterogeneity to predict glycemic levels and real-time risk of hypo-/hyperglycemic by creating specific target functions for these excursions. Results: The majority of the variation (73%) in glucose trajectories was explained by the first two FPCs. Higher order variation in the CGM profiles occurred during weeknights, although variation was higher on weekends. The model has low prediction errors and yields accurate predictions for both glucose levels and real-time risk of glycemic excursions. Conclusions: By identifying these distinct longitudinal patterns as phenotypes, interventions can be targeted to optimize type 1 diabetes management for subgroups at the highest risk for compromised long-term outcomes such as cardiac disease or stroke. Further, the estimated change/variability in an individual’s glucose trajectory can be used to establish clinically meaningful and patient-specific thresholds that, when coupled with probabilistic predictive inference, provide a useful medical-monitoring tool.

More than 5700 children with diabetes attend American Diabetes Association (ADA) camps each year. Training volunteer medical staff has become more challenging given the rapid advances in diabetes technology. Through a prospective, multi-site pilot study at 4 ADA camps, we assessed the efficacy of an educational bundle of online interactive cases with in-situ simulation in preparing medical volunteers for management of type 1 diabetes (T1D). We hypothesized that our curriculum would reduce the workload necessary to manage children with T1D as measured by the NASA-Task load index (TLX), a validated workload assessment tool comprised of 6 self-rated scales; mental, physical, and temporal demand, performance, effort, and frustration. No statistical difference in change in workload was observed between the intervention and control groups (Table 1). However, both groups were small and had different experiences prior to camp. The reduction in temporal demand reported by the intervention group by the end of camp may signal an impact among medical providers. Future interventions, with larger, more balanced groups, could evaluate timing of TLX change and the effect on medical staff’s camp experience and patient care. Disclosure E.S. Atwood: Research Support; Self; American Diabetes Association. N.M. Sheanon: Research Support; Self; American Diabetes Association. S. Amanat: None. J.C. Khoury: None. M. Klein: None.

Introduction Although the administration of free Nicotine Replacement Therapy (NRT) is effective in helping smokers quit, the feasibility, acceptability and safety of this practice have not been examined in the emergency setting of the pediatric emergency department (PED) or urgent care (UC). We examined the characteristics of parental smokers who were interested and eligible for free NRT during their child's emergency visit and the uptake, usage, and associated side effects of NRT use. Methods We analyzed data from 377 parental smokers who were randomized to receive cessation counseling and free NRT as part of an emergency visit-based randomized controlled trial. Parents interested in NRT were screened for medical contraindications; eligible parents were given a 6-week supply of NRT patches or lozenges during their child's emergency visit and offered another supply 6 weeks later. We conducted Wilcoxon rank-sum tests and chi-squared tests to address our main study objective. Results The majority of parents were female (87.5%), non-Hispanic Black (52.5%), and mean (SD) age was 33.1 (8.2) years. A total of 252 (66.8%) parents were interested in receiving NRT. Compared to uninterested parents, interested parents were more likely to: be older [33.6 (8.2) vs 31.9 (8.2), years]; be non-Hispanic Black (54.0% vs 49.6%); have older children [5.5 (5.0) vs 4.2 (4.6)]; have a higher readiness to quit [7.0 (2.4) vs 5.2 (2.6)]; and have a child being evaluated in UC compared to the PED (72.4% vs 56.5%). A total of 53 (21%) interested parents had >1 NRT contraindications. At 6 weeks, 94 (79.0%) parents reported some ≥NRT usage and 50 (53.2%) requested an additional 6-week supply. There were no serious adverse events and 5 (5.3%) reported minor side effects. Conclusions Parental smokers in the emergency setting are interested in receiving free NRT, the majority use it, and use is not associated with adverse side effects. The emergency visit may be an optimal time to offer NRT to parental smokers.

Introduction: The standard workup of thyroid nodules concerning for malignancy includes fine-needle aspiration (FNA). In 2015, the American Thyroid Association (ATA) guidelines for the management of pediatric thyroid nodules recommended that all nodules with a Bethesda III cytology undergo surgical resection. Objectives: To correlate a Bethesda III cytology with histologic and clinical outcomes to determine the relevance of the ATA recommendations, and to evaluate whether Thyroid Imaging Reporting and Data System (TI-RADS) scoring could identify Bethesda III nodules at a lower risk of malignancy. Methods: A retrospective chart review of patients who had undergone thyroid nodule FNA from 2008 to 2018 was performed. Malignancy rates were determined for each Bethesda category. The reference standard was histopathology or 2-year follow-up of imaging outcomes for nonoperative cases. Ultrasound exams of Bethesda III nodules were reviewed and TI-RADS scores assigned. Results: A total of 143 FNA samples from 128 patients were identified. The mean age was 14.9 years (range 7–22). Twenty-two (15%) of the FNA samples were Bethesda III; the malignancy rate was 38%. A TI-RADS score was assigned in 20 of the 22 Bethesda III nodules. ROC analysis found an optimal cut-off for malignancy prediction of ≥7 points (risk category TR5). The negative predictive value was 85.7% (95% CI 35.9–99.6) and the positive predictive value was 83.3% (95% CI 57.2–98.2). Conclusion: Although, at baseline, thyroid nodules with a Bethesda III classification carry a moderate risk of malignancy in the pediatric population, TI-RADS scoring can identify nodules with a lower risk within this group. If validated by larger studies, this can inform decision making and reduce unneeded surgery.

Background. Characterizing maternal glucose sampling over the course of the entire pregnancy is an important step toward improvement in prediction of adverse birth outcome, such as preterm birth, for women with type 1 diabetes mellitus (T1DM). Objectives. To characterize the relationship between the gestational glycemic profile and risk of preterm birth using a joint modeling approach. Methods. A joint model was developed to simultaneously characterize the relationship between a longitudinal outcome (daily blood glucose sampling) and an event process (preterm birth). A linear mixed effects model using natural cubic splines was fitted to predict the longitudinal submodel. Covariates included mother’s age at last menstrual period, age at diabetes onset, body mass index, hypertension, retinopathy, and nephropathy. Various association structures (value, value plus slope, and area under the curve) were examined before selecting the final joint model. We compared the joint modeling approach to the time-dependent Cox model (TDCM). Results. A total of 16,480 glucose readings over gestation (range: 50-260 days) with 32 women (28%) having preterm birth was included in the study. Mother’s age at last menstrual period and age at diabetes onset were statistically significant (beta = 1.29, 95% CI 1.10, 1.72; beta = 0.84, 95% CI 0.62, 0.98) for the longitudinal submodel, reflecting that older women tended to have higher mean blood glucose and those with later diabetes onset tended to have a lower mean blood glucose level. The presence of nephropathy was statistically significant in the event submodel (beta = 2.29, 95% CI 1.05, 4.48). Cumulative association parameterization provided the best joint model fit. The joint model provided better fit compared to the time-dependent Cox model (DIC JM=19,895; DIC TDCM=19,932). Conclusion. The joint model approach was able to simultaneously characterize the glycemic profile and assess the risk of preterm birth and provided additional insights and a better model fit compared to the time-dependent Cox model.

Background and Purpose— Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods— Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results— Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215–242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163–185) in 2015 ( P P Conclusions— Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.

Osteoporosis is a major problem in patients with Duchenne muscular dystrophy (DMD), due to glucocorticoid therapy and muscle weakness. Evidence on which to base optimal prevention and treatment strategies, including bisphosphonate use, in DMD are limited. Our objective was to describe bone health outcomes of oral alendronate treatment in patients with DMD and glucocorticoid-induced osteoporosis. We retrospectively studied 54 patients treated between 2005 and 2017, and assessed changes in dual-energy x-ray absorptiometry (DXA) whole body and lumbar spine bone mineral density and content, and lateral distal femur bone mineral density. We also examined vertebral fracture development in a subset with serial spine radiographs. Pre-alendronate DXA Z-score trajectories decreased progressively. Over three years post-alendronate initiation, Z-score trajectories improved (p0.01) at most sites compared with pre-alendronate trajectories. Height-adjusted Z-score trajectories for lumbar spine bone mineral density (p = 0.01) and whole body bone mineral content (p = 0.0004) also improved. The positive trajectories did not seem to be sustained long term in those treated up to 6 years. Radiographic vertebral findings in 43 patients appeared stable. In conclusion, oral bisphosphonate therapy using alendronate was associated with improvement of DXA bone health indices during the first three years of treatment, and may help mitigate progression of osteoporosis in glucocorticoid-treated patients with DMD.

Objective Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that cleaves IGFBP-3 and IGFBP-5. Human mutations in PAPPA2 result in short stature with a low percentage of free IGF-I. Little is known about PAPP-A2 levels and the regulation of free IGF-I throughout childhood. We examined PAPP-A2 and intact IGFBP-3 levels in childhood and explored associations between PAPP-A2, free and total IGF-I, and total and intact IGFBP-3 and their relationship to the percentage of free to total IGF-I and anthropometric factors. Design Cross-sectional study at a single center. Methods PAPP-A2, free IGF-I, and intact IGFBP-3 levels were measured in childhood (3–18 years old) and an evaluation of the relationship between these proteins and anthropometric factors. Results In 838 children, PAPP-A2 consistently decreased throughout childhood. In contrast, free IGF-I increased. A pubertal peak in free IGF-I was present in females but was less evident in males. Intact and total IGFBP-3 increased throughout childhood; however, intact IGFBP-3 had a more marked rise than total IGFBP-3. Percent free IGF-I decreased with no distinct pubertal peak. PAPP-A2 levels positively correlated with the percent free IGF-I (Male, Female; r = 0.18, 0.38; P r = −0.58, −0.65; P Conclusions This is the first study to describe serum PAPP-A2 and intact IGFBP-3 in children between 3 and 18 years of age. Our correlative findings suggest that PAPP-A2 is an important regulator of the percent free IGF-I which can be a marker of perturbations in the GH/IGF-I axis.

Background:Female athletes are at an increased risk of developing patellofemoral pain (PFP) relative to male athletes. The unique effects of maturation may compound that risk.Hypothesis/Purpose:The purpose was to evaluate the neuromuscular control mechanisms that are adaptive to pubertal maturation and determine their relative contribution to PFP development. It was hypothesized that aberrant landing mechanics (reduced sagittal-plane and increased frontal- and transverse-plane kinematics and kinetics) would be associated with an increased risk for PFP.Study Design:Cohort study; Level of evidence, 2.Methods:There were 506 high school female athletes who completed a detailed medical history, the Anterior Knee Pain Scale, and a knee examination for the diagnosis of PFP and attended follow-up appointments. Athletes performed a drop vertical jump task instrumented with force plates, and biomechanical measures generated from standard 3-dimensional biomechanical analyses were used to classify participants into high- or low-risk knee and hip landing profiles for the development of PFP. The biomechanical measures used in the knee landing profile included sagittal-plane knee range of motion, peak knee abduction angle, peak knee abduction moment, and peak-to-peak transverse-plane knee moment. The biomechanical measures used in the hip landing profile included sagittal-plane hip range of motion, peak hip extensor moment, peak abductor moment, and peak hip rotator moment. Testing was conducted at sport-specific preseason appointments over the course of 2 years, and changes in pubertal status, landing profile, and PFP development were documented.Results:Female athletes with high-risk hip landing profiles experienced increased hip flexion and decreased abductor, rotator, and extensor moments. Participants with high-risk hip landing profiles who transitioned to postpubertal status at follow-up had higher odds (odds ratio, 2.1 [95% CI, 1.1-4.0]; P = .02) of moving to a low-risk hip landing profile compared with those who had not reached postpubertal status at follow-up. Participants with high-risk knee landing profiles experienced decreased knee flexion and increased knee abduction, external abductor, and external rotator moments. Pubertal maturation was not associated with a change in the high-risk knee landing profile at follow-up.Conclusion:The progression from prepubertal to postpubertal status may have a protective effect on high-risk hip mechanics but no similar adaptations in high-risk knee mechanics during maturation. These data indicate that before puberty, maladaptive hip mechanics may contribute to PFP, while aberrant knee mechanics associated with PFP are sustained throughout the maturational process in young female athletes.

Background Patients with diagnoses of high-grade carotid stenosis are often placed on antiplatelet therapy and undergo carotid endarterectomy (CEA) during their hospital stay. There is intersurgeon variability in offering CEA to patients specifically on the potent antiplatelet agent clopidogrel. Methods Utilizing the Premier database, data from adults with principal discharge diagnosis of stroke, transient ischemic attack (TIA), or carotid artery stenosis or occlusion without stroke/TIA (CAS) who had a CEA during the same hospital stay in 2014 were analyzed. Recent clopidogrel or aspirin use was defined as within 3 days before CEA. Univariate and multivariate analyses were used to examine the association of age, race, gender, symptomatic versus asymptomatic carotid stenosis, academic versus non-academic center, and regions of the United States with recent antiplatelet use before CEA. Results There were 15,381 patients (median age, 71 years, interquartile range 65–78; 42% females) with stroke, TIA, or CAS who had a CEA during the same hospital stay in 2014 within the Premier databse. Of these, 2570 patients (16.7%) received clopidogrel, 4992 (32.5%) received aspirin but no clopidogrel, and 7819 (50.8%) received no clopidogrel/aspirin immediately before CEA. Younger patient age, treatment at a non-academic center, symptomatic carotid stenosis, and being in the Northeast or South were associated higher odds of being on clopidogrel therapy prior to CEA. Conclusions Across the United States, 1 in 6 patients was on clopidogrel therapy prior to undergoing a CEA. Patients with symptomatic carotid stenosis were most likely to be on clopidogrel therapy prior to their CEA. Future systematic analysis of differences in outcomes and safety events are needed.

OBJECTIVE Osteoporosis is considered a comorbidity of adult women with Turner syndrome (TS). Limited data are available on fracture prevalence in girls and women with this diagnosis. We aimed to determine the prevalence of fractures in individuals with TS in the United States and identify risk factors for fracture. DESIGN Girls and women with TS were invited to participate in an anonymous, self-report, national survey from November 2016 to March 2017. Non-TS controls were obtained through direct contacts of TS participants. RESULTS During childhood (0-12 years), adolescence (13-25 years) and young adulthood (26-45 years), there was no difference between TS and controls in fracture prevalence. Girls and women with TS were more likely to report upper extremity fractures, whereas controls were more likely to report phalangeal fractures. Older women (>45 years) with TS were more likely to fracture than non-TS controls (P = .01). Balance problems were more common in individuals with TS than controls (26.5% vs 14.8%, P = .0006). In TS, those reporting balance problems were 54% more likely to have a prior fracture than those without balance problems (OR=1.54, 95% CI 1.03, 2.30), even after controlling for age. There was no significant association between balance problems and fractures among controls. CONCLUSIONS In a nationwide survey, there was no difference in fracture prevalence in younger women with TS compared with controls. However, the location of fractures differed. After controlling for age, impaired balance was associated with an increased fracture risk in TS and may be an underrecognized risk factor for fracture in this population.

We previously published rates of pediatric stroke using our population-based Greater Cincinnati Northern Kentucky Stroke Study (GCNK) for periods July 1993–June 1994 and 1999. We report population-based rates from 2 additional study periods: 2005 and 2010. We identified all pediatric strokes for residents of the GCNK region that occurred in July 1, 1993–June 30, 1994, and calendar years 1999, 2005, and 2010. Stroke cases were ascertained by screening discharge ICD-9 codes, and verified by a physician. Pediatric stroke was defined as stroke in those

Context: An estimated 40 million school-aged children (age range = 5−18 years) participate annually in sports in the United States, generating approximately 4 million sport-related injuries and requiring 2.6 million emergency department visits at a cost of nearly $2 billion.Objective: To determine the effects of a school-based neuromuscular training (NMT) program on sport-related injury incidence across 3 sports at the high school and middle school levels, focusing particularly on knee and ankle injuries.Design: Randomized controlled clinical trial.Setting: A total of 5 middle schools and 4 high schools in a single-county public school district.Patients or Other Participants: A total of 474 girls (222 middle school, 252 high school; age = 14.0 ± 1.7 years, height = 161.0 ± 8.1 cm, mass = 55.4 ± 12.2 kg) were cluster randomized to an NMT (CORE; n = 259 athletes) or sham (SHAM; n = 215 athletes) intervention group by team within each sport (basketball, soccer, and volleyball).Intervention(s): The CORE intervention consisted of exercises focused on the trunk and lower extremity, whereas the SHAM protocol consisted of resisted running using elastic bands. Each intervention was implemented at the start of the season and continued until the last competition. An athletic trainer evaluated athletes weekly for sport-related injuries. The coach recorded each athlete-exposure (AE), which was defined as 1 athlete participating in 1 coach-directed session (game or practice).Main Outcome Measure(s): Injury rates were calculated overall, by sport, and by competition level. We also calculated rates of specific knee and ankle injuries. A mixed-model approach was used to account for multiple injuries per athlete.Results: Overall, the CORE group reported 107 injuries (rate = 5.34 injuries/1000 AEs), and the SHAM group reported 134 injuries (rate = 8.54 injuries/1000 AEs; F1,578 = 18.65, P < .001). Basketball (rate = 4.99 injuries/1000 AEs) and volleyball (rate = 5.74 injuries/1000 AEs) athletes in the CORE group demonstrated lower injury incidences than basketball (rate = 7.72 injuries/1000 AEs) and volleyball (rate = 11.63 injuries/1000 AEs; F1,275 = 9.46, P = .002 and F1,149 = 11.36, P = .001, respectively) athletes in the SHAM group. The CORE intervention appeared to have a greater protective effect on knee injuries at the middle school level (knee-injury incidence rate = 4.16 injuries/1000 AEs) than the SHAM intervention (knee-injury incidence rate = 7.04 injuries/1000 AEs; F1,261 = 5.36, P = .02). We did not observe differences between groups for ankle injuries (F1,578 = 1.02, P = .31).Conclusions: Participation in an NMT intervention program resulted in a reduced injury incidence relative to participation in a SHAM intervention. This protective benefit of NMT was demonstrated at both the high school and middle school levels.

BACKGROUND AND PURPOSE: Limited information is available regarding differences in neuroimaging use for acute stroke work-up. Our objective was to assess whether race, sex, or age differences exist in neuroimaging use and whether these differences depend on the care center type in a population-based study. MATERIALS AND METHODS: Patients with stroke (ischemic and hemorrhagic) and transient ischemic attack were identified in a metropolitan, biracial population using the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Multivariable regression was used to determine the odds of advanced imaging use (CT angiography/MR imaging/MR angiography) for race, sex, and age. RESULTS: In 2005 and 2010, there were 3471 and 3431 stroke/TIA events, respectively. If one adjusted for covariates, the odds of advanced imaging were higher for younger (55 years or younger) compared with older patients, blacks compared with whites, and patients presenting to an academic center and those seen by a stroke team or neurologist. The observed association between race and advanced imaging depended on age; in the older age group, blacks had higher odds of advanced imaging compared with whites (odds ratio, 1.34; 95% CI, 1.12–1.61; P < .01), and in the younger group, the association between race and advanced imaging was not statistically significant. Age by race interaction persisted in the academic center subgroup (P < .01), but not in the nonacademic center subgroup (P = .58). No significant association was found between sex and advanced imaging. CONCLUSIONS: Within a large, biracial stroke/TIA population, there is variation in the use of advanced neuroimaging by age and race, depending on the care center type.

Background We aimed to compare sex-specific associations between cardiovascular risk factors and diabetes mellitus (DM) among patients with acute ischemic stroke (AIS) in the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS). Methods The GCNKSS ascertained AIS cases in 2005 and 2010 among adult (age ≥20 years) residents of a biracial population of 1.3 million. Past and current stroke risk factors were compared between those with and without DM using chi-square and multiple logistic regression to examine sex-specific profiles. Results There were 3515 patients with incident AIS; 1919 (55%) were female, 697 (20%) were black, and 1146 (33%) had DM. Among both women and men with DM, significantly more were obese, and had hypertension, high cholesterol, and coronary artery disease (CAD) compared with those without DM. For women with AIS, in multivariable sex-specific adjusted analyses, older age was associated with a decreased odds of having DM (aOR=0.88, 95%CI 0.80-0.98). For women with CAD, the odds of DM were increased (aOR=1.76, 95%CI 1.33-2.32). Age and CAD were not significant factors in differentiating the profiles of men with and without DM. Conclusions Women with DM had strokes at a younger age, whereas no such age difference existed in men. As opposed to men, women with DM were also more likely to have CAD compared with those without DM, suggesting a sex difference in the association between DM and vascular disease. These findings may suggest a need for more aggressive risk factor management in diabetic women.

Objective ST2 is a member of the toll-like receptor superfamily that can alter inflammatory signaling of helper T-cells. We investigated whether soluble ST2 (sST2) could independently predict outcome and hemorrhagic transformation (HT) in the setting of stroke. Methods We measured sST2 in patients enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. 646 patients had plasma samples collected at the time of hospital admission and 210 patients had a second sample collected 48 h after stroke onset. Functional outcome was assessed using the modified Rankin Scale (mRS), with good and poor outcomes defined as mRS 0-2 and 3-6, respectively. HT was classified using ECASS criteria. The relationships between sST2, outcome, and HT were evaluated using multivariable logistic regression, Kaplan–Meier survival analysis and receiver operating characteristic curves. Results 646 patients were included in the analysis (mean age 69 years; 44% women), with a median NIHSS of 5 [IQR: 2–12]. The median sST2 level on hospital admission was 35.0 ng/mL [IQR: 25.7–49.8 ng/mL] and at 48 h it was 37.4 ng/mL [IQR 27.9–55.6 ng/mL]. sST2 was independently associated with poor outcome (OR: 2.77, 95% CI: 1.54–5.06; P = 0.003) and mortality (OR: 3.56, 95% CI: 1.58–8.38, P = 0.001) after multivariable adjustment. Plasma sST2 was also associated with hemorrhagic transformation after adjustment for traditional risk factors (OR: 5.58, 95% CI: 1.40–37.44, P = 0.039). Interpretation Soluble ST2 may serve as a prognostic biomarker for outcome and hemorrhagic transformation in patients with acute stroke. ST2 may link neuroinflammation and secondary injury after stroke.

Background: The effects of targeted neuromuscular training (TNMT) on movement biomechanics associated with the risk of anterior cruciate ligament (ACL) injuries are currently unknown. Purpose/Hypotheses: To determine the effectiveness of TNMT specifically designed to increase trunk control and hip strength. The hypotheses were that (1) TNMT would decrease biomechanical and neuromuscular factors related to an increased ACL injury risk and (2) TNMT would decrease these biomechanical and neuromuscular factors to a greater extent in athletes identified as being at a high risk for future ACL injuries. Study Design: Controlled laboratory study. Methods: Female athletes who participated in jumping, cutting, and pivoting sports underwent 3-dimensional biomechanical testing before the season and after completing TNMT. During testing, athletes performed 3 different types of tasks: (1) drop vertical jump, (2) single-leg drop, and (3) single-leg cross drop. Analysis of covariance was used to examine the treatment effects of TNMT designed to enhance core and hip strength on biomechanical and neuromuscular characteristics. Differences were also evaluated by risk profile. Differences were considered statistically significant at P < .05. Results: TNMT significantly increased hip external rotation moments and moment impulses, increased peak trunk flexion, and decreased peak trunk extension. Athletes with a high risk before the intervention (risk profile III) had a more significant treatment effect of TNMT than low-risk groups (risk profiles I and II). Conclusion: TNMT significantly improved proximal biomechanics, including increased hip external rotation moments and moment impulses, increased peak trunk flexion, and decreased peak trunk extension. TNMT that focuses exclusively on proximal leg and trunk risk factors is not, however, adequate to induce significant changes in frontal-plane knee loading. Biomechanical changes varied across the risk profile groups, with higher risk groups exhibiting greater improvements in their biomechanics.

Patients with Spinal Muscular Atrophy (SMA) are at risk for poor bone health. The prevalence of fractures, low areal bone mineral density (aBMD; Z-score ≤−2.0) of the lateral distal femur and of osteoporosis by SMA subtype is not known. We aimed to describe the natural history of bone health in patients with SMA prior to bisphosphonate treatment. We reviewed data from 85 eligible patients with SMA ages 12 months to 18 years, seen at a single institution between January 2005 and July 2016. Fracture history was reported at annual clinic visits. aBMD was obtained from dual energy x-ray absorptiometry scans of the lumbar spine, total body, and lateral distal femur. 85% of patients had aBMD Z-scores ≤−2.0 SD and were progressively lower with worsening SMA severity. Longitudinal aBMD Z-scores of the lateral distal femur decreased with age. Fractures occurred in 38% (32/85) of patients with the femur being the most common location (25 of 57 fractures). Thirteen percent of patients fulfilled criteria for osteoporosis. Low aBMD and femur fractures are highly prevalent in all SMA subtypes from a young age; however, few patients met the criteria for osteoporosis. Poor bone health may be an under-recognized comorbidity of SMA.

Backgound Nontraumatic subdural hematomas are a common indication for inpatient hospitalization in the United States, yet there is little high-quality evidence regarding which patients should receive surgical or medical treatment. We sought to assess variation in surgical management and medical treatment with steroids for nontraumatic subdural hematomas across the United States. Methods Using the Premier database, we analyzed patients with a primary discharge diagnosis of nontraumatic subdural hematoma in 2014. International Classification of Diseases, Ninth Revision, procedure codes were used to identify patients who underwent surgical management, and pharmacy data were used to identify patients treated with dexamethasone. Univariable and multivariable analyses were used to examine the association of age, race, sex, academic versus nonacademic center, and regions of the United States with conservative or surgical management. Results There were 3915 inpatient hospitalizations for nontraumatic subdural hematomas in 2014 in the Premier database, of whom 1860 (47.5%) underwent surgery, and 360 (9.2%) underwent treatment with dexamethasone, either as a primary treatment or as an adjuvant to surgery. Older age, female sex, and being managed outside of the Western U.S. region were associated with a lower likelihood of undergoing surgical management on multivariable analysis; only younger age was associated with a greater likelihood of being treated with dexamethasone. Conclusions There is considerable variability in surgical management of nontraumatic subdural hematomas across the United States based on age, sex, and region. Future studies should explore the reasons for the variability and attempt to better clarify indications for surgical management of subdural hematomas.

OBJECTIVE: Previously we reported that ischemic stroke incidence is declining over time for men but not women. We sought to describe temporal trends of sex differences in incidence of transient ischemic attack (TIA) within the same large, biracial population. METHODS: Among the population of 1.3 million in the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) region, TIAs among area residents (≥20 years old) were identified at all local hospitals. Out of hospital cases were ascertained using a sampling scheme. First-ever cases and first within each study period for a patient were included in incidence rates. All cases were physician-adjudicated. Incidence rates (during 7/93-6/94 and calendar years 1999, 2005, and 2010) were calculated using the age-, race-, and sex-specific number of TIAs divided by the GCNKSS population in that group; rates were standardized to the 2010 U.S. population. T-tests with Bonferroni correction were used to compare rates over time. RESULTS: There were a total of 4746 TIA events; 53% were female, and 12% were black. In males, incidence decreased from 153 (95%CI 139-167) per 100,000 in 1993/4 to 117 (95%CI 107-128) in 2010 (p0.05). CONCLUSIONS: Within the GCNKSS population, TIA incidence decreased significantly over time in males but not females, data which parallels trends in ischemic stroke in the GCNKSS over the same time period. Future research is needed to determine if these sex differences in incidence over time continue past 2010.

Background While air pollution has been associated with depression and anxiety in adults, its impact on childhood mental health is understudied. Objective We examined lifetime exposure to traffic-related air pollution (TRAP) and symptoms of depression and anxiety at age 12 years in the Cincinnati Childhood Allergy and Air Pollution Study cohort. Methods We estimated exposure to elemental carbon attributable to traffic (ECAT), a surrogate of diesel exhaust, at birth, age 12 years, and average exposure throughout childhood, using a validated land use regression model. We assessed depression and anxiety at age 12 years by parent report with the Behavior Assessment System for Children-2, and by child report with the Child Depression Inventory-2 (CDI-2) and the Spence Children's Anxiety Scale (SCAS). Associations between TRAP at birth, age 12 years, and childhood average and mental health outcomes were estimated using linear regression models adjusting for covariates including parent depression, secondhand smoke exposure, race, household income, and others. Results Exposure to ECAT was not significantly associated with parent-reported depression or anxiety. However, exposure to ECAT at birth was associated with increased child-reported depression and anxiety. Each 0.25 µg/m3 increase in ECAT was associated with a 3.5 point increase (95% CI 1.6–5.5) in CDI-2 scores and 2.3 point increase (95% CI 0.8–3.9) in SCAS total anxiety scores. We observed similar associations between average childhood ECAT exposures but not for concurrent exposures at age 12. Conclusions TRAP exposure during early life and across childhood was significantly associated with self-reported depression and anxiety symptoms in children. The negative impact of air pollution on mental health previously reported among adults may also be present during childhood.

Background: More information is needed about modifiable child tobacco smoke exposure (TSE) patterns in racially diverse parental smokers to tailor interventions designed to help parents quit smoking and reduce their child’s TSE. Our objectives were to determine whether there were differences in smoking and TSE patterns based on parental race and child age and whether these patterns differed based on child age within black and white parental smokers. Secondary objectives were to assess the relationship between parental perceptions about the effects of smoking and the benefits of quitting on their child based on child age, race, and reported TSE patterns and to examine biochemically verified TSE levels by child age, race, and parent-reported TSE patterns. Methods: Participants (N = 415) were non-Hispanic black and non-Hispanic white parental smokers, mean age (standard deviation [SD]) = 31.2 (7.2) years, who visited the Pediatric Emergency Department (PED) or Urgent Care (UC) with their child, mean age (SD) = 4.7 (4.6) years. Parents reported sociodemographics, smoking, and child TSE patterns. We conducted chi-square tests, independent t-tests, and general linear regression models to answer our primary objectives and linear regression models to answer our secondary objectives. Results: Parents were 56.1% non-Hispanic black; 87.5% women; mean (SD) number of cigarettes smoked/day was 10.5(6.8). A higher proportion of parents with younger children Conclusions: Children of parental smokers who visit the PED/UC were highly tobacco smoke exposed. Both black and white parental smokers with younger children were more likely to enforce smoking bans, but younger children had higher TSE levels than older children. Interventions that target this group of parental smokers with younger children may be more effective than interventions geared to all parental smokers.

Introduction: Previously, we reported that stroke incidence in the young (age < 55) significantly increased in both blacks and whites over four study periods between 1993 and 2010. Here we further describe this temporal trend, adding data from 2015. Methods: The Greater Cincinnati/Northern Kentucky region includes 2 southern Ohio and 3 contiguous Northern Kentucky counties (estimated population, 1.3 M). Our study determined first-ever hospital-ascertained strokes that occurred in the population from 7/1/93 to 6/30/94 and in calendar years 1999, 2005, 2010, and 2015 by screening ICD9 (and ICD10, in 2015) codes of all inpatient and emergency department visits. Cases were abstracted by study nurses and verified by study physicians. Results for 2015 are preliminary. The denominator for the calculation of incidence rates (in those aged ≥20 years) was extracted from the U.S. Census Bureau website (www.census.gov). Age- and race -specific incidence rates with 95% confidence intervals (CI) were calculated assuming a Poisson distribution. We tested for differences in age trends using Student’s t-test, X 2 , and Poisson regression as appropriate. Results: The mean± SD age of stroke was 71.3±13.6 in 1993-94, 70.9±14.4 in 1999, 68.4±15.5 in 2005, 68.5±15.6 in 2010, and 68.7±15.4 in 2015 (p Discussion: The disturbing trend of increasing stroke in the young (age < 55) has leveled off slightly since 2010 but is still of great public health significance as younger strokes carry the potential for greater lifetime burden of disability. Further study is needed to determine the reasons for these results, including examination of race-specific trends.

Aims/hypothesis: We sought to determine the impact of intrauterine exposure to excessive gestational weight gain (GWG) on overweight/obesity in adolescent/young adult offspring of women with type 1 diabetes mellitus (TIDM). Methods: In 2008, a pilot study was conducted among 19 randomly-selected adolescent and adult offspring of mothers with TIDM who participated in the Diabetes in Pregnancy Program Project (DiP) between 1978 and 1995. Body mass index (BMI)-specific Institute of Medicine (IOM) guidelines for gestational weight gain (GWG) were defined as: 12.5–18.0 kilograms (kg) GWG; 11.5–16.0 kg GWG: 7.0–11.5 kg GWG; 5.0–9.0 kg GWG, for women classed as underweight, normal, overweight and obese according to pre-pregnancy BMI, respectively. Generalized estimating equations were used to estimate adjusted odds ratios (aOR, [95% confidence intervals, CI]) for overweight/obesity among offspring, related to IOM adherence, adjusting for pre-pregnancy BMI and mean maternal daily insulin units/kg body weight. Results: Mean age of offspring at follow-up was 20.3 ± 3.3 years, 12(63%) were male, 4(21%) Black and 12(63%) overweight/obese. There were 9(82%) overweight/obese offspring among the 11 mothers who exceeded IOM guidelines for GWG compared with 3(38%) overweight/obese offspring among the 8 mothers with GWG within guidelines. Exceeding vs. adhering to IOM guidelines (OR = 7.50, [95%CI: 0.92–61.0]) and GWG per kilogram (OR = 1.39, [95%CI: 0.98–1.97]) were associated with offspring overweight/obesity at follow-up. Conclusions/interpretation: Our pilot study suggests potential long-term implications of excessive GWG on metabolic health in offspring of mothers with TIDM, warranting future research examining the health impact of GWG in this population.

Women with pre-gestational diabetes have a high rate of large for gestational age (LGA) babies compared to women without diabetes. In particular, there is a high rate of asymmetric LGA defined as ponderal index (PI) &gt, 90th percentile for gestational age. We examined the association of birth weight and PI, with body mass index (BMI) and obesity status in adulthood, in a cohort of offspring of women with pre-gestational diabetes. The women participated in the Diabetes in Pregnancy (DiP) study at the University of Cincinnati from 1978 to 1995. The offspring of these women are the cohort participating in an observational study being conducted at Cincinnati Children&rsquo, s Hospital Medical Center. Once located, the offspring were invited to come in for a one-day clinic visit to assess anthropometrics, and their metabolic, renal and cardiovascular status. Linear and logistic regression was used to assess the association between birth weight and PI with current BMI. We report on 107 offspring. A statistically significant association was found between offspring current BMI with birth PI (&beta, = 1.89, 95%CI 0.40&ndash, 3.38), and between offspring current obesity status and birth asymmetric LGA (aOR = 2.44, 95%CI 1.01&ndash, 5.82). This is consistent with in utero &ldquo, metabolic programming&rdquo

BackgroundPoststroke guidelines recommend moderate-intensity, continuous aerobic training (MCT) to improve aerobic capacity and mobility after stroke. High-intensity interval training (HIT) has been shown to be more effective than MCT among healthy adults and people with heart disease. However, HIT and MCT have not been compared previously among people with stroke.ObjectiveThe purpose of this study was to assess the feasibility and justification for a definitive randomized controlled trial (RCT) comparing HIT and MCT in people with chronic stroke.DesignA preliminary RCT was conducted.SettingThe study was conducted in a cardiovascular stress laboratory and a rehabilitation research laboratory.PatientsAmbulatory people at least 6 months poststroke participated.InterventionBoth groups trained 25 minutes, 3 times per week, for 4 weeks. The HIT strategy involved 30-second bursts at maximum-tolerated treadmill speed alternated with 30- to 60-second rest periods. The MCT strategy involved continuous treadmill walking at 45% to 50% of heart rate reserve.MeasurementsMeasurements included recruitment and attendance statistics, qualitative HIT acceptability, adverse events, and the following blinded outcome variables: peak oxygen uptake, ventilatory threshold, metabolic cost of gait, fractional utilization, fastest treadmill speed, 10-Meter Walk Test, and Six-Minute Walk Test.ResultsDuring the 8-month recruitment period, 26 participants consented to participate. Eighteen participants were enrolled and randomly assigned to either the HIT group (n=13) or the MCT group (n=5). Eleven out of the 13 HIT group participants attended all sessions. Participants reported that HIT was acceptable and no serious adverse events occurred. Standardized effect size estimates between groups were moderate to very large for most outcome measures. Only 30% of treadmill speed gains in the HIT group translated into overground gait speed improvement.LimitationsThe study was not designed to definitively test safety or efficacy.ConclusionsAlthough further protocol optimization is needed to improve overground translation of treadmill gains, a definitive RCT comparing HIT and MCT appears to be feasible and warranted.

Background: Hypovitaminosis D exists postburn. However, evidence-based guidelines for vitamin D repletion are unknown. This investigation examined differences between D2 and D3 supplementation on outcome in children with burn injuries. Methods: Fifty patients with total body surface area burn of 55.7% ± 2.6% and full-thickness injury of 40.8% ± 3.8% were enrolled, ranging in age from 0.7–18.4 years. All participants received multivitamin supplementation per standardized clinical protocol. In addition, 100 IU/kg D2, D3, or placebo was administered daily during hospitalization using a randomized, double-blinded study design. Assay of total 25-hydroxyvitamin D (D25), 1,25-dihydroxyvitamin D (D1,25), 25-hydroxyvitamin D2 (25-OH-D2), 25-hydroxyvitamin D3 (25-OH-D3), and parathyroid hormone (PTH) was performed at 4 preplanned time intervals (baseline, midpoint, discharge, and 1 year postburn). Differences in vitamin D status were compared over time and at each specific study interval. Results: There were no sig...

OBJECTIVE Missed diagnoses of acute ischemic stroke (AIS) in the ED may result in lost opportunities to treat AIS. Our objectives were to describe the rate and clinical characteristics of missed AIS in the ED, to determine clinical predictors of missed AIS, and to report tissue plasminogen (tPA) eligibility among those with missed strokes. METHODS Among a population of 1.3 million in a five-county region of southwest Ohio and northern Kentucky, cases of AIS that presented to 16 EDs during 2010 were identified using ICD-9 codes followed by physician verification of cases. Missed ED diagnoses were physician-verified strokes that did not receive a diagnosis indicative of stroke in the ED. Bivariate analyses were used to compare clinical characteristics between patients with and without an ED diagnosis of AIS. Logistic regression was used to evaluate predictors of missed AIS diagnoses. Alternative diagnoses given to those with missed AIS were codified. Eligibility for tPA was reported between those with and without a missed stroke diagnosis. RESULTS Of 2,027 AIS cases, 14.0% (n = 283) were missed in the ED. Race, sex, and stroke subtypes were similar between those with missed AIS diagnoses and those identified in the ED. Hospital length of stay was longer in those with a missed diagnosis (5 days vs. 3 days, p < 0.0001). Younger age (adjusted odds ratio [aOR] = 0.94, 95% confidence interval [CI] = 0.89 to 0.98) and decreased level of consciousness (LOC) (aOR = 3.58, 95% CI = 2.63 to 4.87) were associated with higher odds of missed AIS. Altered mental status was the most common diagnosis among those with missed AIS. Only 1.1% of those with a missed stroke diagnosis were eligible for tPA. CONCLUSION In a large population-based sample of AIS cases, one in seven cases were not diagnosed as AIS in the ED, but the impact on acute treatment rates is likely small. Missed diagnosis was more common among those with decreased LOC, suggesting the need for improved diagnostic approaches in these patients.

Background Although statin therapy is associated with reduced stroke and mortality risk, some studies report that higher lipid levels are associated with improved outcomes following ischemic stroke. Aims We examined the association of hyperlipidemia (HLD) combined with statin therapy on all-cause mortality in stroke patients. Methods All stroke patients in the Greater Cincinnati Northern Kentucky region of ∼1.3 million were identified using ICD-9 discharge codes in 2005 and 2010. Stroke patients with and without HLD were categorized based on their reported statin use at baseline or discharge into three groups: no-HLD/no-statins, HLD/no-statins, and HLD/on-statins. Cox proportional hazards model was used to estimate the risk of mortality at 30 days, 1 year, and 3 years poststroke. Results Overall, 77% (2953) of the 3813 ischemic stroke patients were diagnosed with HLD and 72% ( n = 2123) of those patients were on statin medications. The mean age was 70.0 ± 14.6 years, 56% were women, and 21% were black. In adjusted analyses, the HLD/no-statins group showed 35% (adjusted hazard ratio (aHR) = 0.65, 95% CI: 0.46–0.92), 27% (aHR = 0.73, 95% CI: 0.59–0.90), and 17% (aHR = 0.83, 95% CI: 0.70–0.97) reduced risk of mortality at 30 days, 1 year, and 3 years, respectively, poststroke, compared with no-HLD/no-statins group. The HLD/on-statins group showed an additional 17% significant survival benefit at 3 years poststroke compared with HLD/no-statins group. Conclusions A diagnosis of HLD in ischemic stroke patients is associated with reduced short- and long-term mortality, irrespective of statin use. Statin therapy is associated with significant, additional long-term survival benefit.

Gestational diabetes mellitus (GDM) has increased dramatically in the past 20 years together with the obesity epidemic. Mirroring the increase in incidence of GDM is increasing use of endocrine disrupting chemicals (EDCs). EDCs are structurally similar to endogenous hormones and interfere with synthesis, secretion, activity, or elimination of natural hormones, resulting in adverse health effects, including diabetes, obesity, developmental disorders, etc. Although the association between bisphenol A (BPA), a well-studied EDC, and type 2 diabetes has been repeatedly investigated in epidemiological and animal studies, there is a dearth of studies examining EDCs and GDM. In fact, the impact of environmental toxins on perinatal health outcomes has largely been overlooked.Recognizing this research gap, the American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and International Federation of Gynecology and Obstetrics recently joined leading scientists and clinicians in a call for action to prioritize research in the consequences of exposure to toxic environmental agents on women's health. Evidence is emerging to suggest signaling molecules and EDCs are involved in the control of microRNA (miRNA) expression in trophoblast cells. We reviewed existing scientific evidence of EDCs as a risk factor for GDM as well as the potential role of miRNA in this association.

Residential injury is a leading cause of morbidity and mortality in US children. Rates and types of injury vary by child age but little is known about injury risk based on child cognitive and motor abilities. The objective of this study was to determine whether cognitive or motor development in young children is associated with residential injury.We employed data from Health Outcomes and Measures of the Environment (HOME) Study. Parent report of medically attended injury was obtained at regular intervals from 0 to 42 months. Child development was assessed at 12, 24 and 36 months using Bayley Scales of Infant and Toddler Development, 2nd edition, which generates both mental developmental index (MDI) and a psychomotor developmental index (PDI). Injury risk was modelled using multivariable logistic regression as function of child's MDI or PDI. Effects of MDI and PDI on injury risk were examined separately and jointly, adjusting for important covariates.Children with cognitive delay (MDI77) were at significantly higher risk of injury than children without cognitive delay (OR=3.7, 95% CI 1.4 to 10.5, p=0.012). There was no significant association of PDI with injury. There was, however, significant interaction of MDI and PDI (p=0.02); children with cognitive delay but normal motor development were at significantly higher risk of injury than children with normal cognitive and motor development (OR=9.6, 95% CI 2.6 to 35.8, p=0.001).Children with cognitive delays, especially those with normal motor development, are at elevated risk for residential injuries. Injury prevention efforts should target children with developmental delays.NCT00129324; post-results.

Objective To determine the association between placental weight (PW) and large for gestational age (LGA) in women with type 1 diabetes mellitus (T1DM) and whether glycemic control modifies the association. Study Design In a retrospective analysis of a cohort of women with T1DM, poor glycemic control was defined as glycohemoglobin A1(HbA1)≥ 8.5% (≥2 standard deviations [SD] above mean), and LGA as birth weight > 90th percentile, according to gestation, race, and sex. Multivariable logistic regression was used for analysis. Stratified analyses (HbA1