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Background: Though stroke risk factors such as substance use may vary with age, less is known about trends in substance use over time or about performance of toxicology screens in young adults with stroke. Methods: Using the Greater Cincinnati Northern Kentucky Stroke Study, a population-based study in a 5-county region comprising 1.3 million people, we reported the frequency of documented substance use (cocaine/marijuana/opiates/other) obtained from electronic medical record review, overall and by race/gender subgroups among physician-adjudicated stroke events (ischemic and hemorrhagic) in adults 20 to 54 years of age. Secondary analyses included heavy alcohol use and cigarette smoking. Data were reported for 5 one-year periods spanning 22 years (1993/1994–2015), and trends over time were tested. For 2015, to evaluate factors associated with performance of toxicology screens, multiple logistic regression was performed. Results: Overall, 2152 strokes were included: 74.5% were ischemic, mean age was 45.7±7.6, 50.0% were women, and 35.9% were Black. Substance use was documented in 4.4%, 10.4%, 19.2%, 24.0%, and 28.8% of cases in 1993/1994, 1999, 2005, 2010, and 2015, respectively ( P trend Conclusions: In a population-based study of young adults with stroke, documented substance use increased over time, and documentation of substance use was higher among Black compared with White individuals. Further work is needed to confirm race-based disparities and trends in substance use given the potential for bias in screening and documentation. Findings suggest a need for more standardized toxicology screening.

Background and ObjectivesThere is a rising incidence of infective endocarditis–related stroke (IERS) in the United States attributed to the opioid epidemic. A contemporary epidemiologic description is necessary to understand the impact of the opioid epidemic on clinical characteristics of IERS. We describe and analyze trends in the demographics, risk factors, and clinical features of IERS.MethodsThis is a retrospective cohort study within a biracial population of 1.3 million in the Greater Cincinnati/Northern Kentucky region. All hospitalized patients with hemorrhagic or ischemic stroke were identified and physician verified from the 2005, 2010, and 2015 calendar years using ICD-9 and ICD-10 codes. IERS was defined as an acute stroke attributed to infective endocarditis meeting modified Duke Criteria for possible or definite endocarditis. Unadjusted comparison of demographics, risk factors, outcome, and clinical characteristics was performed between each study period for IERS and non-IERS. An adjusted model to compare trends used the Cochran-Armitage test for categorical variables and a general linear model or Kruskal-Wallis test for numerical variables. Examination for interaction of endocarditis status in trends was performed using a general linear or logistic model.ResultsA total of 54 patients with IERS and 8,204 without IERS were identified during the study periods. Between 2005 and 2015, there was a decline in rates of hypertension (91.7% vs 36.0%;p= 0.0005) and increased intravenous drug users (8.3% vs 44.0%;p= 0.02) in the IERS cohort. The remainder of the stroke population demonstrated a significant rise in hypertension, diabetes, atrial fibrillation, and perioperative stroke. Infective endocarditis status significantly interacted with the trend in hypertension prevalence (p= 0.001).DiscussionFrom 2005 to 2015, IERS was increasingly associated with intravenous drug use and fewer risk factors, specifically hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with fewer comorbidities.

Background: TIAs serve as an opportunity to identify and modify risk factors and to prevent future events. Given known epidemiologic differences in strokes by race and sex, our objective was to investigate the rates of prior TIAs among those with incident ischemic stroke (IS) in the GCNKSS. Methods: We included all physician adjudicated, incident IS among adults age ≥20 years in the GCNKSS, a population-based stroke surveillance study in a 5-county region of southern Ohio/ northern Kentucky, in 2005, 2010, and 2015. We calculated the frequency of cases in which a TIA (sudden onset of focal neurologic symptoms lasting ≤ 24 hours) was documented in the 365 days prior to IS. Frequencies and proportions of prior TIA were compared by sex, race, and age, and location at which patients sought care for their TIA was described. Finally, multivariable logistic regression was performed to investigate demographic and clinical predictors of cases in which TIA preceded stroke; covariates were chosen a priori. Results: We included 5310 IS events; mean age was 69.7 (SD 14.8) years, 54.7% were female, and 20.4% were Black. A total of 351 patients (6.6%) had a documented TIA the year preceding their IS. Overall, 42.2% did not seek care for their TIA, 21.6% called 911 and/or came to the ED, 6.0% saw a PCP, and 6.6% sought other care. In 22.5% of cases, location of care was unknown. In adjusted results, older age, female sex, history of hypertension, and CAD were associated with having had a prior TIA, while Black race was not. NIHSS was inversely associated with prior TIA (Table). Prior TIAs were similar between study years. Conclusions: We conservatively estimate that ≥ 6% of patients with first-ever IS had a TIA in the preceding year, though underreporting is likely. Many patients did not report seeking care for the TIA, suggesting missed opportunities for risk factor modification. Further research is needed to understand the implications of sex and race differences in frequencies of prior TIA.

Background: Monitoring changes in ischemic stroke severity at the population level is important as changes in risk factors and clinical treatments could influence stroke severity. We describe trends in the distribution of NIHSS across 3 time periods in a population-based epidemiologic stroke study. Methods: In 2005, 2010, and 2015 all adult acute ischemic strokes occurring within the Greater Cincinnati area presenting to 15 hospitals were ascertained using discharge codes (ICD-9 433-436; IDC-10 I63-I68, G45-46). Following physician verification, confirmed ischemic stroke cases underwent chart abstraction including estimation of a retrospective (rNIHSS) score at presentation. Descriptive statistics (rNIHSS median, IQR) were generated by survey year, demographics, and medical history. Using a binary definition of stroke severity (median rNIHSS score &gt 4 versus &lt 4), multivariable logistic regression was used to estimate changes in stroke severity over time, adjusting for potential confounders. Random effects were used to account for multiple admissions occurring in the same subject. Results: The number of ischemic stroke admissions in the 2005, 2010, and 2015 surveys was 1778, 1903, and 1933, respectively (Table). The median (IQR) rNIHSS scores were 3 (2-7), 3 (1-6), and 2 (1-6) across the 3 surveys, respectively; the proportion of admissions with rNIHSS &gt 4 was 48%, 39% and 37%, respectively. After adjusting for demographics, medical history and pre-stroke function, compared to 2005, the odds ratio for more severe stroke was 0.69 (95% CI= 0.60-0.79, p=0.001) in 2010 and 0.63 (95% CI= 0.55-0.73, p=0.001) in 2015. Conclusions: In this population- based study there was a statistically significant change in the severity of ischemic stroke hospitalizations with increases in the proportion of milder strokes over time. Potential reasons for this change need to be explored but could include changes in risk factors, clinical treatments or diagnostic approach.

Introduction: Primary prevention reduces the burden of acute ischemic stroke (AIS), yet cerebrovascular risk factors (RF) remain underdiagnosed in certain populations. We aimed to identify predictors of undiagnosed RF among patients with cerebrovascular ischemic events in a large bi-racial population. Methods: Individuals 20 years and older with an incident TIA or AIS from the population-based Greater Cincinnati/Northern Kentucky 2015 stroke study period were screened for inclusion. We included all hospital ascertained, physician-verified cases of AIS and TIAs. Outpatient and ED-only cases were excluded. Abstracted medical record data included determination of newly diagnosed hypertension (HTN), diabetes mellitus (DM), hyperlipidemia (HLD) or atrial fibrillation (AF). Multivariable models were used to identify predictors for each undiagnosed RF. Model variables included: age, sex, race, insurance status and number of cerebrovascular RF (additionally including coronary artery disease and smoking). Results: A total of 1604 ischemic events were included (1485 stroke, 119 TIA) with 52.9% female; 22.4% Black; median age 70 (IQR 59, 82)). Only 6% (n=102) had no history of RF. The prevalence of each undiagnosed RF was: HTN 4.1%; HLD 7.9%; DM 3.1%; AF 3.2%. In unadjusted bivariate analysis, uninsured/unknown status was predictive of undiagnosed HTN (OR = 3.97, 95% CI 1.48, 10.68; p =.006) and HLD (OR=5.53, 95% CI 2.68, 11.4; p Table 1 ). No relationship was found with race. Conclusions: The most consistent predictor for an undiagnosed RF was absence of other RF and lack of insurance, both suggestive of suboptimal cardiovascular screening in this population. Further studies assessing known but undertreated RF and socioeconomic factors could be of benefit.

Background: Ischemic stroke is the 5 th leading cause of death in the US. As a measure of stroke severity, initial NIHSS has been used to predict clinical outcome. We sought to identify the optimal cut-points of NIHSS at initial presentation that are associated with higher 30-day mortality. Methods: In 2005, 2010, and 2015 all hospitalized, first acute ischemic stroke events occurring within the Greater Cincinnati area were ascertained. Potential ischemic stroke cases underwent chart abstraction and physician adjudication, including retrospective NIHSS score (range 0 - 42) based on clinical findings at initial presentation. Descriptive statistics for NIHSS were estimated by study year, demographics, and medical history. Data regarding mortality was obtained from the National Death Index. The Contal and O’Quigley method based on a modified log-rank test statistic was used to determine cut-points of the NIHSS score associated with 30-day mortality, and hazard ratios were obtained from Cox models with adjustment for sex, race, and age. Results: In 2005, 2010, and 2015 there were 1704, 1818 and 1852 ischemic stroke events with 30-day mortality rates of 10.5%, 9.6% and 9.0%, respectively. Optimal cut-points of NIHSS 16 were identified. Across all 3 periods, 3431 (84.5%) cases had NIHSS 0-8, 352 (8.7%) had NIHSS 9-16 and 274 (6.8%) >16. Kaplan Meier Survival Curves for the 3 NIHSS groups are shown in the Figure. Strokes with NIHSS >16 at initial presentation were associated with a 15-fold (HR with 95% CI: 13, 19) increase in the risk of death at 30-days compared to those with NIHSS Discussion: NIH Stroke Scale scores are a reliable predictor of mortality, with higher NIHSS scores having higher risk of death. The cut points reported identify subgroups of stroke patients with dramatically different prognoses. Future studies should assess if this excess mortality risk among severe strokes persists after the more widespread implementation of thrombectomy beyond 2015.

Background: Previous studies spanning the 1990s-2010s have inconsistently identified a decline in 30-day stroke case-fatality rate (CFR), and little is known about trends in longer term stroke CFR over that period. We studied temporal trends in 30-day and 5-year CFRs in the well-defined Greater Cincinnati/Norther Kentucky (GCNK) stroke population. Methods: The NIH-funded GCNK Stroke Study is a population-based study conducted in a 5-county region that is representative of the USA in terms of Black race, income, and education. The study ascertained all strokes in 1993/4, 1999, 2005, 2010, and 2015 using well-validated methods. All stroke subtypes were included: ischemic strokes (IS), intracerebral hemorrhages (ICH), and subarachnoid hemorrhages (SAHs). Deaths were identified via the National Death Index. Cox proportional hazards models were used to assess all-cause fatality, by subtype, to examine temporal trends adjusting for age, sex, and race. Results: A total of 10372 stroke cases were ascertained over the five study periods (8428 IS, 443 SAH, and 1501 ICH). IS patients did not demonstrate a decline in 30-day CFRs over time, but did show a nonsignificant decrease in 5-year CFR. Among IS patients, female sex was associated with a lower 5-year CFR, whereas Black individuals had a lower 30-day CFR but a higher 5-year CFR. For ICH, there was a small increase in both 30-day and 5-year CFR in later study periods, although this did not reach significance in all years. SAH showed a lower 30-day CFR over time but no change in 5-year CFR. Older age was associated with a higher 30-day and 5-year CFR in all subtypes. Discussion: Despite widespread advances in post-stroke care, adjusted 5-year CFR has not clearly improved for any stroke subtype and may have slightly worsened for ICH. 30-day CFR has shown a modest improvement among SAH patients. Future studies should investigate why Black individuals with IS experience lower early CFR but a higher late CFR.

Background: Knowledge of stroke risk factors (RF) and warning signs (WS) may improve adherence to primary stroke prevention and encourage more rapid presentation after symptom onset. As a result, improving stroke knowledge has been a major public health focus. We sought to study trends in stroke knowledge between 1996 and 2021 in a well-defined population. Methods: Surveys were conducted in 1996, 2000, 2005, 2011, 2016, and 2021 in the 5-county Greater Cincinnati Northern Kentucky region, a population of 1.3 million that reflects the USA in terms of Black race, income, and educational attainment. Respondents were selected to reflect the age, race and sex distribution of the local ischemic stroke population. Potential subjects were contacted using random-digit dialing (with adjustment for cell phone use after 2005) and asked open-ended questions regarding stroke WS and RF knowledge. Correct answers for all years were determined based upon current AHA guidelines and public health messaging. Trends in knowledge were then evaluated over time adjusting for age, Race, sex, and education. Multiple logistic regression models and a cumulative model were used for analysis. Results: Over the 25-year period, 12,322 surveys were completed. After adjustment for age, sex, Race, and education, RF and WS knowledge significantly increased between 1996 and 2021 (P Discussion: While stroke RF and WS knowledge has overall improved since 1996, knowledge remains suboptimal and some gains may have been lost in recent years. More research on the most effective methods for improving stroke awareness is needed.

This study proposes a Bayesian joint model with extended random effects structure that incorporates nested repeated measures and provides simultaneous inference on treatment effects over time and drop-out patterns. The proposed model includes flexible splines to characterize the circadian variation inherent in blood pressure sequences, and we assess the effectiveness of an intervention to resolve pediatric obstructive sleep apnea. We demonstrate that the proposed model and its conventional two-stage counterpart provide similar estimates of nighttime blood pressure but estimates on the mean evolution of daytime blood pressure are discrepant. Our simulation studies tailored to the motivating data suggest reasonable estimation and coverage probabilities for both fixed and random effects. Computational challenges of model implementation are discussed.

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.

ImportanceFor walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization.ObjectiveTo assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke.Design, Setting, and ParticipantsThis multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled.InterventionsParticipants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated.Main Outcomes and MeasuresThe main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training.ResultsOf 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, −9 to 33 m]; mean difference, 15 m [95% CI, −13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue.Conclusions and RelevanceThese findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains.Trial RegistrationClinicalTrials.gov Identifier: NCT03760016

A frequent problem in longitudinal studies is that data may be assessed at subject-selected, irregularly spaced time-points, resulting in highly unbalanced outcome data, inducing bias, especially if availability of data is directly related to outcome. Our aim was to develop a multivariate joint model in a mixed outcomes framework to minimize irregular sampling bias. We demonstrate using blood glucose monitoring throughout pregnancy and risk of preterm birth among women with type 1 diabetes mellitus. Blood glucose measurements were unequally spaced and intensity of sampling varied between and within individuals over time. Multivariate linear mixed effects submodel for the longitudinal outcome (blood glucose), Poisson model for the intensity of glucose sampling, and logistic regression model for binary process (preterm birth) were specified. Association between models is captured through shared random effects. Markov chain Monte Carlo methods were used to fit the model. The multivariate joint model provided better prediction, compared with a joint model with a multivariate linear mixed effects submodel (ignoring intensity of glucose sampling) and a two-stage model. Most association parameters were significant in the preterm birth outcome model, signifying improvement of predictive ability of the binary endpoint by sharing random effects between glucose monitoring and preterm birth. A simulation study is presented to illustrate the effectiveness of the multivariate joint modeling approach.

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.

Background: In acute stroke, reducing delays between symptom onset and treatment can improve outcomes. While in-hospital delays have been successfully reduced, pre-hospital delays have persisted. Public health campaigns have attempted to reduce these delays by increasing stroke symptom awareness, but it is unknown whether these efforts have improved the percentage of patients presenting early after symptom onset. Methods: We performed an analysis of the Greater Cincinnati/Northern Kentucky Stroke Study, a population-based study of all stroke patients in a large geographic area. We looked at the 2010 and 2015 study years. All stroke cases (ischemic and hemorrhagic) presenting to the 16 regional EDs were included. We examined the time between symptom onset and ED arrival times, dichotomized into ≤3.5 hours and >3.5 hours. In cases without a clear onset, estimates were derived using wake-up or last known well times. Comparisons were made using multivariable logistic regression. Results: Among 4633 total stroke patients, 1359 patients presented early (29%). Results of the multivariable analysis are shown in the Table . There was no improvement the rate of early presentation in 2015 (aOR 1.01, 95% CI 0.89-1.16). EMS utilization, night arrival, higher NIHSS scores, and better premorbid function were associated with early arrival. Patients who lived alone were less likely to arrive early. Conclusion: We found no evidence for improvement in the rate of early presentation over the years studied. Work is needed to address other barriers to early hospital arrival, including underutilization of EMS.

Background: Antithrombotic medications (AT) are often withheld before procedures to reduce risk of bleeding. In 2005, members of our team reported that 5.2% of ischemic strokes were associated with the withdrawal of AT in the preceding 60 days. Subsequently, new medications, including DOACs, have become widely used. Given changing prescription and practice patterns we sought to compare rates of stroke in the setting of antithrombotic withdrawal in 2010 and 2015. Methods: The GCNKSS is a population-based stroke study from the Greater Cincinnati region. In 2005, 2010, and 2015, we captured all strokes in the Greater Cincinnati/Northern Kentucky 5 county area by screening ICD9 codes 430-436 and ICD10 (2015) codes I60-I68, and G45-46. Study nurses abstracted all cases and physicians adjudicated each event. Data regarding the withdrawal of AT and timing were captured. 2005 data was included as a reference. Fisher’s exact test was used to examine differences by years. Results: In 2010 and 2015, 4768 cases of ischemic stroke were identified. Across the study periods, those that were on AT at time of stroke versus those who stopped AT Conclusions: The withdrawal of AT is associated with 228 (4.8%) of ischemic strokes within 60 days in our study population. These rates remain consistent across our study periods. This highlights that despite new agents, stroke in the setting of AT withdrawal remains consistent and the decision to stop AT must be carefully considered.

Objective: Prediction of the long-term outcome in Ischemic Stroke (IS) patients can have a significant impact on design of clinical trials and on patients’ care. We studied gene expression (GE) as a novel biomarker to provide an accurate prediction of 90-day outcome in IS patients. Methods: RNA from 72 samples from 2 peripheral blood draws (at ≤3 and 24 hrs post IS onset) was analyzed on Affymetrix U133 Plus 2.0 microarrays. These represented samples from 36 CLEAR trial IS patients that had blood drawn within 3 hrs of stroke onset and were then treated with tPA with or without eptifibatide. The samples were split into derivation (n=25) and validation (n=11) sets. We identified the differential GE in blood at 24 hrs and the difference in GE between 24 hrs and 3 hrs post IS that was associated with 90-day post stroke outcome using the model: GE = μ + NIHSS_24hr+mRS_90day+ ε. Good outcome was defined as mRS 0-2; Poor - as mRS 3-5. Logistic regression was used to derive a biomarker classifier. Results: Using 24 hrs GE, we identified 14 probesets (12 genes) with the highest discriminative power for predicting outcome. The model achieved recall (the probability of correctly identifying the patients with Good outcome) of 0.88 and specificity (the probability of correctly identifying the patients with Poor outcome) of 0.67 in the validation set (The AUC-ROC = 0.88). The biomarker genes were enriched in immune responses such as IL and cytokine signaling. Among the predictors were genes important for stroke and repair after stroke (e.g., MACC1 , GDF11 ). MACC1 has been considered as a potential treatment target for IS with a protective role in hypoxia-induced human brain microvascular endothelial cells. GDF11 plays a role in brain repair after IS. We also determined how the change of GE from 3 hrs to 24 hrs would predict the 90-day outcome. A panel of ten genes was able to predict outcome in the validation set (recall= 1, specificity = 0.67, AUC-ROC=0.88). These included AVPR1A , which mediates platelet aggregation and release of coagulation factors and exacerbates brain inflammatory response to injury. Conclusion: This pilot study suggests gene expression can be used to predict stroke outcome. Some of the genes may serve as potential therapeutic targets.

Background: Prior studies have demonstrated a rising incidence of infective endocarditis related stroke (IERS) in the US due to the opioid epidemic. The Greater Cincinnati/Northern Kentucky (GCNK) region has one of the highest opioid abuse rates in the nation. A modern epidemiologic description is necessary to understand the impact of the opioid epidemic on the clinical phenotype of IERS. Methods: Using the GCNK Stroke Study, all patients hospitalized with IERS in 2005, 2010, and 2015 were abstracted and physician reviewed. IERS was defined as an acute stroke clinically attributed to infective endocarditis in patients meeting modified Duke Criteria for possible or definite endocarditis. Comparison between years were by chi-square or Fisher’s exact test for categorical variables; ANOVA or Kruskal-Wallis test for numerical variables. Cochran-Armitage test was used to examine trend. Secondary analysis compared characteristics between intravenous drug users (IVDU) and non-IVDU. Results: A total of 54 patients with IERS were identified in 2005, 2010, and 2015. Over the period, there was a significant decline in hypertension (91.7% in 2005, 36.0% in 2015; p=0.0005) and increase in IVDU (8.3% in 2005, 44.0% in 2015; p=0.02). They trended towards increased white race, younger age, and fewer vascular risk factors. Compared to non-IVDU, IVDU were significantly younger (41.1±14.1vs 63.1±14.3 years; p Conclusion: From 2005 to 2015, IERS was increasingly associated with IVDU and an absence of hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with less comorbidities.

Background: Anticoagulant-associated intracerebral hemorrhage (AA-ICH) quintupled in the Greater Cincinnati/Northern Kentucky (GC/NK) region from 1988 to 1999 in association with increasing warfarin use. Direct-acting oral anticoagulants (DOACs), available in 2010, have evidence of less bleeding risk, while atrial fibrillation detection rates have increased. We sought to determine if rates of AA-ICH continued to increase in the last decade within a large, bi-racial population. Methods: We identified all patients, 20 years or older, hospitalized with first-ever intracerebral hemorrhage (ICH) in GC/NK region in 1993/4, 1999, 2005, 2010 and 2015. AA-ICH was defined as ICH in patients prescribed warfarin, heparin or low molecular weight heparin, or a DOAC at the time of their ICH. Incidence rates were age-, sex- and race-adjusted to the 2010 US population. Change over time was tested using regression. All-cause case fatality was adjusted for age, sex and race and trend over time evaluated using a general linear model. Results: There was no significant change over time in the incidence rate for total ICH or AA-ICH from 1993 through 2015 (Table). As compared to ICH patients without anticoagulant use, patients with AA-ICH were more likely to be older, white, have hypertension, diabetes mellitus, hyperlipidemia, prior ischemic stroke and atrial fibrillation, but less likely to smoke. The age-, sex- and race-adjusted 30-day case fatality for ICH overall and AA-ICH also did not change significantly from 1993/4 to 2015 (Table). Warfarin utilization increased in our ICH population from 1993/4 (7.6%) to 2005 (17.7%), then decreased through 2015 (11.8%/DOAC 6.4%); p Conclusion: Despite increased incidence rates of AA-ICH in the late 1980s to 1990s, we observed no overall change in incidence or case-fatality rate from AA-ICH over the full 20-year period despite higher rates of atrial fibrillation detection which may be explained by higher rates of DOAC (vs warfarin) use.

Introduction: Endovascular (EVT) eligibility estimates using population-based, NIH-funded Greater Cincinnati Northern Kentucky (GCNK) Stroke Study 2010 data have been reported. Given the evolving EVT landscape, we present updated estimates of annual EVT eligibility using the 2015 GCNK epidemiological data and extrapolate to the 2021 US census. We project the potential increase in eligible patients in the US for each possible expanded indication with a randomized trial currently planned/underway. Methods: We ascertained all hospitalized AIS patients ≥18 years old in 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46 within GCNK population; all cases were physician-reviewed. Patients presenting within 0-5 hrs of last known well (LKW) were considered EVT eligible if they had a pre-stroke mRS1 (for 0-5 hrs) or ≥2 (for 5-23 hrs), or larger core. Estimates of vessel occlusion and favorable imaging were applied based on literature review and expert opinions. The derived estimates were age, race and sex-adjusted to the 2015 US adult population and extrapolated to 2021 population. Results: Among the 1.3 million total (1.05m adult) GCNK population in 2015, 2741 adults had an ischemic stroke and 2176 had data available for this analysis. A total of 1978 presented within 23 hrs of LKW, and 1233 within 0-5 hrs of LKW. Further results are outlined in the figure. Conclusions: It is estimated 18,484 adult patients in the US in 2021 meet strict EVT eligibility criteria. An estimated 15,699 patients with low NIHSS, 9621 with unfavorable imaging, and 28,107 with pre-stroke disability may become eligible for EVT in the future annually. US stroke systems should be optimized to handle all EVT-eligible stroke patients both now and in the future.

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.

The growth hormone and insulin-like growth factor (IGF) system is integral to human growth. Genome-wide association studies (GWAS) have identified variants associated with height and located near the genes in this pathway. However, mechanisms underlying these genetic associations are not understood. To investigate the regulation of the genes in this pathway and mechanisms by which regulation could affect growth, we performed GWAS of measured serum protein levels of IGF-I, IGF binding protein-3 (IGFBP-3), pregnancy-associated plasma protein A (PAPP-A2), IGF-II and IGFBP-5 in 838 children (3–18 years) from the Cincinnati Genomic Control Cohort. We identified variants associated with protein levels near IGFBP3 and IGFBP5 genes, which contain multiple signals of association with height and other skeletal growth phenotypes. Surprisingly, variants that associate with protein levels at these two loci do not colocalize with height associations, confirmed through conditional analysis. Rather, the IGFBP3 signal (associated with total IGFBP-3 and IGF-II levels) colocalizes with an association with sitting height ratio (SHR); the IGFBP5 signal (associated with IGFBP-5 levels) colocalizes with birth weight. Indeed, height-associated single nucleotide polymorphisms near genes encoding other proteins in this pathway are not associated with serum levels, possibly excluding PAPP-A2. Mendelian randomization supports a stronger causal relationship of measured serum levels with SHR (for IGFBP-3) and birth weight (for IGFBP-5) than with height. In conclusion, we begin to characterize the genetic regulation of serum levels of IGF-related proteins in childhood. Furthermore, our data strongly suggest the existence of growth-regulating mechanisms acting through IGF-related genes in ways that are not reflected in measured serum levels of the corresponding proteins.

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.

Background: Genome-wide association studies (GWAS) have identified thousands of common genetic variants associated with human height, implicating hundreds of genes and loci. However, the mechanisms by which many of these genetic variants contribute to human adult height are still unknown. Integrating knowledge of the interaction between genetic background and protein levels in childhood can provide insights into the biology of human growth. Objective: To investigate biological associations at height-associated loci in the GH-IGF signaling pathway. Methods: We used data from the Cincinnati Genomic Control Cohort, a community-based cohort comprised of 1,020 children. The study was approved by the institutional review board at Cincinnati Children’s Hospital Medical Center. Protein levels for free and total IGF-I, intact and total IGFBP-3, PAPP-A2, IGF-II, and IGFBP-5 were measured by ELISA in 839 children (ages 3-18 years) and corrected for age- and sex-effects. We associated protein-level phenotypes using plink qassoc and stratified by sex and population, in ~870 European- and African-descent individuals. Meta-analyses were performed using the METAL fixed-effects model. GWAS of anthropometric traits were performed in the UK Biobank of ~400,000 individuals using Bolt-LMM, or curated from publicly available summary statistics. Results: We identified 17 independent genome-wide significant protein-level-associated loci (p