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Anxiety disorders emerge during childhood and adolescence and are frequently preceded by subsyndromal anxiety symptoms. Environmental toxicants, including gestational polybrominated diphenyl ether (PBDE) exposure, are associated with neuropsychiatric sequelae; however, the role of PBDEs as risk factors for anxiety in adolescence is unclear.Using data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort enrolled from 2003 to 2006, we investigated the relationship between gestational serum PBDE concentrations and anxiety symptoms in adolescents (N = 236). We measured five PBDE congeners (PBDE-28, -47, -99, -100, and -153) at 16 ± 3 weeks of gestation and calculated their sum (∑PBDE). We assessed self-reported anxiety symptoms using the Screen for Child Anxiety Related Emotional Disorders (SCARED) and depressive symptoms using the Children's Depression Inventory (CDI-2) at age 12 years. We estimated the associations of maternal PBDE concentrations with child anxiety and depressive symptoms using multivariable linear regression and modified Poisson regression. Covariates included child sex, maternal race, maternal age at delivery, maternal marital status, maternal education, and household income at the 12-year study visit as well as maternal depressive and anxiety symptoms. Sensitivity analyses were performed to control for maternal lead and mercury at delivery.After adjusting for predetermined covariates, each doubling in maternal PBDE concentrations was associated with increased SCARED scores (e.g., for ∑PBDE, SCARED total score, β = 1.6 95% confidence interval [CI]: 0.3-2.9, p = .019) and a nonsignificant increase in depressive symptoms (e.g., for CDI total score, β = .8, 95% CI: -0.2-1.8, p = .11).Gestational serum PBDE concentrations just before mid-pregnancy and during a period of active cortical and limbic neurogenesis, synaptogenesis and myelogenesis may be a risk factor for developing anxiety symptoms in early adolescence.

Persons with stroke often have difficulty achieving target heart rate during graded exercise testing (GXT), which is known to limit test sensitivity for detecting clinically relevant cardiac conditions. A novel Recumbent Stepper 3-minute (RS 3Min) 'all out' test may increase sensitivity of stress testing after stroke.The purpose of this study was to determine the feasibility of adding a Recumbent Stepper 3Min test after a GXT among persons' post-stroke.A within-subject, non-randomized, repeated measures design.Rehabilitation research laboratory and cardiovascular stress laboratory PARTICIPANTS: Fifteen participants with chronic stroke (56.7 ± 9.6 years; 6.4 ± 4.3 years post stroke; 8 male).All participants randomly completed 1) a symptom-limited treadmill GXT; and 2) a symptom-limited RS GXT followed by a RS 3Min critical power test.Heart rate, ratings of perceived exertion, oxygen consumption, respiratory exchange ratio, and power output measured continuously during each test. Blood pressure measured every two minutes and or immediately post exercise. P value set at p0.05 from omnibus test for a significant difference among protocols.The RS 3Min test had a significantly higher rate of achieving target HR compared to the RS GXT (9/14 vs 4/14, p=0.02) and was not significantly different from the TM GXT (9/14 vs 5/14, p=0.09). Minimum power output during the RS 3Min was significantly higher than peak power output during the RS GXT (110 ± 41 W vs. 84 ± 22 W, p=0.02) with 12/15 subjects reaching a VO2 plateau.While additional studies with randomized designs are needed, a novel RS 3Min 'all out' test appears to be a promising method for enhancing test sensitivity in cardiovascular screening post-stroke, while providing a potentially valid measure of critical power. This article is protected by copyright. All rights reserved.

To determine the frequency of gastric sensory motor symptoms in youth with type 1 diabetes.A prospective cross-sectional study was performed to evaluate symptoms of delayed gastric emptying in participants with type 1 diabetes, ages 12 to 25 years, using the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire. Additionally, a 5 year (1/2015-12/2019), retrospective study was completed on all gastric emptying scans (GES) performed in youth at our institution.A total of 359 participants (mean age 17.7±3.33 years) with type 1 diabetes completed the GCSI questionnaire. Compared with non-responders, responders were more likely to be non-Hispanic white (90% vs 86%, p=.003) and female (58% vs 44%, p0.0001) with a lower HbA1c (8.1±1.8 vs. 9.0±2.1, p0.0001). At least one GI symptom was reported in n=270 (75%) of responders, of which nausea was the most common (71%). A GCSI score of ≥1.9 suggestive of more severe gastrointestinal symptoms was reported in 17% of responders. Participants with scores ≥ 1.9 were older (19.1±3.0 vs 17.8±3.3 years, p=0.01). In the retrospective study (n=778) underwent GES, 29 participants had type 1 diabetes and 11 (38%) were found to have delayed gastric emptying.Gastrointestinal symptoms related to gastric sensory motor abnormalities are seen in youth and young adults with type 1 diabetes. Especially for those with higher GCSI scores, earlier recognition and referral may be warranted.

IntroductionFor walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. This trial aimed to determine 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 chronic stroke.MethodsPersons with chronic post-stroke gait dysfunction at three centers were randomized to high-intensity interval training (HIT) or moderate intensity aerobic training (MAT), each involving 45 minutes of treadmill and overground walking exercise with a physical therapist, 3 times per week for 12 weeks. The HIT protocol used repeated 30 second bursts of walking at maximum safe speed, alternated with 30-60 second recovery periods, targeting an average aerobic intensity above 60% heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40 ± 5% HRR, progressing by 5% HRR every 2 weeks, up to 60% HRR as tolerated. Blinded assessment at baseline and after 4, 8 and 12 weeks of training included the 6-minute walk test (6MWT) as the primary measure of walking capacity.ResultsRandomized participants (N=55) attended 1,675 (85%) of 1,980 planned treatment sessions and 197 (90%) of 220 planned testing sessions. No serious adverse events related to study procedures occurred. Compared with MAT, HIT involved significantly higher training speeds (161% vs 96% baseline fastest 10-meter speed, pDiscussionThese findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In chronic stroke, vigorous walking exercise can produce significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks are needed to maximize immediate gains.

Metabolic syndrome (MetS) affects ∼10% of U.S. adolescents. Abdominal obesity is the most prevalent component and may indicate MetS risk in adolescents undergoing weight loss surgery.Assess MetS risk/severity and its association with abdominal obesity (measured by sagittal abdominal diameter, SAD) before and after weight loss surgery in adolescents to determine whether SAD predicts MetS risk in this population.Data were collected in the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study at 5 sites (U.S. children's hospitals) performing weight-loss surgery in adolescents. The current study is a secondary analysis of these data.We examined data collected presurgery through 5 years postsurgery. MetS risk/severity was defined using the MetS severity z score (MetS-z), and MetS prevalence was determined using age-appropriate criteria. Association between SAD and MetS-z was evaluated with an adjusted linear mixed model.Among 228 individuals (75% female, 72% White), mean age 16.5 years and body mass index (BMI) 53 kg/mAbdominal obesity is a key MetS risk marker in youth undergoing weight loss surgery. Both SAD and Met-z measures may be useful for MetS risk assessment and tracking postsurgery changes in this population, but more research is needed to identify effective lifestyle interventions targeting abdominal obesity.

Background: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018. Methods: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge. Results: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1–6.0%; I 2 , 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P 8 (odds ratio, 2.0 [95% CI, 1.1–3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis. Conclusions: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.

Introduction: Turner syndrome (TS) results from a complete or partial loss of the X chromosome and affects 25–50 per 100,000 females. These individuals have characteristic neurocognitive and psychological profiles with an increased lifetime prevalence of mood disorders, such as depression and anxiety. Consensus guidelines recommend the use of psychometrically robust tools to screen for these conditions [Eur J Endocrinol. 2017;177(3):G1–G70 and Gynecol Endocrinol. 2004;19(6):313–9]. We propose a sustainable and informative approach to routine anxiety screening in individuals with TS and describe the prevalence of anxiety, genotype-phenotype associations, and impact of comorbidities on anxiety. Methods: We pilot the use of a self-administered version of the validated Pediatric, Parent Proxy, and Adult Patient-Reported Outcomes Measurement Information System (PROMIS®) Anxiety tool during routine visits to the Cincinnati Children’s Hospital Medical Center (CCHMC) TS clinic from October 2019 to March 2020. Results: Ninety-two eligible TS females, ages 8–62 years, received the PROMIS® Anxiety measure. Elevated anxiety scores, ≥1 standard deviation above the T-score mean, were present in 65% of patients (38% mild, 19% moderate, and 8% severe). Results were discussed during the clinic visit, and referral for further evaluation and treatment was offered. There was no apparent genotype-phenotype association among females with anxiety; however, there appeared to be elevated anxiety symptoms (T-score >60) in those with hearing deficits and also in individuals with three or more medical comorbidities. Of the 55% of patients who filled out the acceptability survey, 88% found the process helpful and ∼50% felt that screening should be performed at least every 6 months. Conclusion: Our study demonstrated a high prevalence of anxiety symptoms within a cohort of 92 females with TS. In alignment with current guidelines, these findings indicate the importance of routine neuropsychological assessments for timely recognition and subsequent management of anxiety, especially as milder presentations may otherwise go unnoticed. We have shown that screening tools, such as the PROMIS® Anxiety measure, can be easily utilized by nonmental health care providers (i.e., endocrinologists) who may see TS patients more frequently and be able to initiate impactful discussions surrounding mental health and further referral to subspecialists for expert management.

Diabetes is the 2nd most common cause of delayed gastric emptying in adults. As a result, patients with type 1 diabetes are at increased risk of gastric motor abnormalities that can include delayed gastric emptying (gastroparesis) and the related symptoms. Limited information exists regarding presence of gastric motility disorders in youth with type 1 diabetes. An improved understanding of whether these gastric motility symptoms are present may influence screening, diagnosis, treatment, and quality of life. A cross sectional study was conducted to assess symptoms suggestive of gastroparesis in pediatric patients with type 1 diabetes using the standardized Gastroparesis Cardinal Symptom Index (GCSI) questionnaire. The GCSI consists of 9 questions to assess the presence and severity of gastric motility symptoms. Severity is rated from none (0) to very severe (5) using a likert scale and three symptom subscale (presence of nausea/vomiting, fullness/early satiety, and bloating). The total GCSI score is calculated as the mean of the three subscales. A GCSI score ≥ 1.9 has been associated with delayed gastric emptying. Initial data from 247 patients with type 1 diabetes; mean±SD age 18.1±3.4 years (range 15-20 years old), 61% female, 90% Caucasian, duration of the disease 8.4 ±5.3 years, A1c 8.1±1.8% who answered the GCSI questionnaire found 190 (77%) had at least one symptom associated with gastric motility disorder. Nausea was the most common symptom (75%) followed by stomach fullness (63%). Of those with at least one positive symptom, 37 (20%) had a score ≥ 1.9. Those with a GCSI score ≥ 1.9 were older (19.5 vs. 17.8, p=0.008), but there was no association with race, sex, body mass index, duration of the disease, or glycemic control, as measured by HbA1c. Gastrointestinal symptoms suggestive of gastric motor abnormalities, as measured by the GCSI questionnaire are present in youth with type 1 diabetes. Older patients may be at higher risk. Disclosure G. Mashali: None. A. A. Kaul: None. L. M. Dolan: None. J. C. Khoury: None. A. S. Shah: None.

Tyrosine kinase inhibitors that target vascular endothelial growth factor receptor [VEGFR-TKI] are a class of targeted therapies approved for treatment of several malignancies and are increasingly used in the pediatric population. Development of hypothyroidism during VEGFR-TKI therapy is well described in adults; however, there are no available data in children. Importantly, hypothyroidism during childhood can negatively impact growth and neurodevelopment. This retrospective study is the first to document frequency and severity of VEGFR-TKI induced hypothyroidism in pediatric and young adult patients. Patients included were ≤25 years of age and treated with at least one VEGFR-TKI between 2010 and 2018 at Cincinnati Children's Hospital Medical Center. After review of clinical and demographic data, 69 patients were identified. Of these, 19 (27.5%) developed thyroid dysfunction defined as Thyroid-stimulating hormone≥5 mIU/mL during therapy. Twelve of those patients had overt hypothyroidism with documentation of low free thyroxine and/or levothyroxine initiation. Mean exposure time to VEGFR-TKI before thyroid dysfunction was 2.8 (0.5-10.4) months. These results suggest moderate risk of developing thyroid dysfunction during VEGFR-TKI therapy in pediatric and young adult patients. Baseline thyroid hormone screening should be performed and repeated frequently during the first year of therapy in the pediatric population.

Background: Hemorrhagic transformation (HT) of ischemic stroke can have devastating consequences, leading to longer hospitalizations, increased morbidity and mortality. We sought to identify the rate of HT in stroke patients not treated with tPA within a large, biracial population. Methods: The GCNKSS is a population-based stroke epidemiology study from five counties in the Greater Cincinnati region. During 2015, we captured all hospitalized strokes by screening ICD-9 codes 430-436 and ICD-10 codes I60-I68, and G45-46. Study nurses abstracted all potential cases and physicians adjudicated cases, including classifying the degree of HT. Patients treated with thrombolytics were excluded. Incidence rates per 100,000 and associated 95% confidence intervals (CI) were estimated for HT cases, age and sex adjusted to the 2000 US population. Multiple logistic regression was used to examine risk factors associated with HT. Results: In 2015, there were 2301 ischemic strokes included in the analysis. Of these 104 (4.5%) had HT; 23 (22.1%) symptomatic, 55 (52.9%) asymptomatic and 26 (25%) unknown. Documented reasons for not receiving tPA in these patients were: time (71, 68.3%), anticoagulant use (1, 1.0%), other (18,17.3%) and unknown (14, 13.5%), which were not significantly different compared to those without HT. Only 29/104 (18.3%) had HT classified as PH-1 or PH-2. The age, sex and race-adjusted rate of HT was 9.8 (7.9, 11.6) per 100,000. The table shows rates of potential risk factors and the adjusted odds of developing HT. 90 day all-cause case fatality for patients with HT was significantly higher, 27.9% vs. 15.7%, p Conclusion: We found that 4.5% of non-tPA treated IS patients had HT. These patients had more severe strokes, were more likely to have abnormal coagulation tests or anticoagulant use, and were more likely to die within 90 days. We also report the first population-based incidence rate of HT in non-tPA treated of 9.8/100,000, a rate similar to the incidence of SAH.

Introduction: A main goal for hospital admission following acute ischemic stroke (AIS) is to establish the mechanism of stroke (MoS) allowing for patient specific secondary prevention of stroke interventions. We previously reported on diagnostic testing trends and MoS determination from 1993 through 2010. We updated this analysis with 2015 data to better understand the effects of trends in diagnostic testing on MoS determination. Methods: Patients with AIS aged > 20 years from all study time periods (Table) of the population based GCNKSS were included. Charts were abstracted in a systematic way for tests performed during the hospital stay. Only first-ever ischemic stroke cases, evaluated in an emergency department were used for this analysis. Stroke experts reviewed these events and adjudicated the mechanism of stroke according to modified TOAST criteria. We looked at and compared trends for testing and MoS. Results: Our analysis included 7226 patients. Basic patient demographics, MoS categories and tests across study periods are detailed in the Table. There were significant increases in EKG (7%), TTE (35%), TEE (7%), HCT (4%), brain MRI (65%), MRA (30%) and CTA (28%). Across study periods, cardioembolic (4.1%), small vessel disease (3%), large artery disease (0.9%) and other (1.5%) MoS increased while unknown MoS decreased (-9.5%). Discussion: From 1993/1994 to 2015 there has been a significant increase of in-hospital testing in AIS and decreases in undetermined MoS. Cardioembolic and small vessel disease MoS categories increased the most. Despite a significant increase in vessel imaging, large artery disease and “other determined” MoS categories are largely unchanged. Further research is required to elucidate the occult MoS underlying the undetermined category. Based on our analysis it appears unlikely to be significantly associated with our current definition of stroke associated with large artery disease defined as ≥ 50% ipsilateral stenosis.

Introduction: The availability of rapid tissue and vessel imaging for TIA has increased, but the utilization rates of these and other diagnostic and management strategies for TIA over time are unknown. Objective: To investigate trends in TIA diagnostic and management strategies over time in the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS). Methods: The GCNKSS is a population-based study of 1.3 million people living in a 5-county area of southern Ohio and Northern Kentucky. For this study, all physician-adjudicated, first-ever cases of TIA (defined clinically as sudden onset of focal symptoms lasting < 24 hours) presenting to an emergency department over five study periods (1993/4, 1999, 2005, 2010, 2015) were included. Use of AHA-recommended aspects of TIA management as well as disposition of TIA patients (admission to hospital or discharge from ED) and length of stay were compared across study periods. Rates of acute infarct on MRI were also reported. Trends were examined using the Cochran-Armitage test for trend. Results: In total, over all study periods, there were 2251 first-ever TIAs. Overall, 14% (n=311) occurred in Black individuals, and 57% (n=1275) occurred in women. Utilization of diagnostic modalities [non-contrast CT brain, vascular imaging (CTA, MRA, or carotid dopplers), tissue imaging (MRI), and echocardiogram] increased significantly over time (all p Conclusions: The management of TIA has changed significantly over time. Utilization of tissue and vessel imaging as well as echocardiogram during the hospital stay has increased; in 2015, the vast majority of patients with TIA in this population-based study received each of these testing modalities and were admitted to a hospital for TIA work-up. Further work is needed to understand the best practices for work-up of suspected TIA.

Background: Substantial practice variability exists with respect to the diagnostic workup and disposition of patients with TIA. Identifying the workup needed to prevent adverse outcomes is critical. We aimed to determine whether there is an association between specific elements of TIA management and outcomes. Methods: The GCNKSS is a population-based study of 1.3 million people living in a 5-county area of southern Ohio/ Northern Kentucky. For this study, all physician adjudicated, first-ever TIAs (clinically defined as sudden onset, focal neurologic symptoms lasting < 24 hours, with or without MRI correlate) presenting to the ED during 2015 were included; those with prior stoke or TIA were excluded. Multivariable logistic regression was performed to investigate associations between specific aspects of TIA management and an adverse outcome, defined as stroke, recurrent TIA, or all-cause mortality within 30 days, adjusted for demographics, co-morbidities, and symptom type and length as classified in the ABCD2 score. Results: In 2015, there were 477 adjudicated first ever TIA events presenting to the ED. Overall, 13% (n=62) occurred in Black individuals and 51% (n=243) in women. Regarding outcomes, 3% (n=16) had a stroke within 30 days, 6% (n=30) had a recurrent TIA within 30 days, and 1% (n=4) died within 30 days (all-cause mortality). 16.4% had acute infarct on MRI. In multivariable analysis, having an MRI was associated with reduced risk of adverse outcome, while performance of vessel imaging, echocardiogram, or admission to hospital were not significantly associated with outcomes (Table). Conclusions: Among common diagnostic and management strategies for TIA, only performance of MRI was associated with a lower likelihood of having an adverse outcome within 30 days. Possible contributors include variability in care between hospitals with differing MRI performance rates and changes in management of risk factors based on MRI results, though further work is needed.

Background: Functional outcomes are improved when AIS patients receive faster treatment. The first medical contact for many AIS patients is with emergency medical services (EMS) providers. We hypothesize that AIS treatment is faster when EMS providers suspect stroke. Methods: We performed a retrospective analysis of the Greater Cincinnati/Northern Kentucky Stroke Study, a comprehensive study of stroke patients in a large geographical area with 1.3 million inhabitants whose demographics are representative of the United States. We compared AIS patients age ≥18 years transported by EMS in 2015 with an EMS impression of “stroke” or “weakness/numbness” to those with other EMS impressions. Primary outcome was thrombolysis rate, and secondary outcomes were times from EMS scene arrival to ED arrival, CT, and treatment and times from ED arrival to CT and treatment. Chi-square and Mann-Whitney U-tests were used to compare treatment rates and times, respectively. Logistic regression (for rates) and median regression (for times) adjusted for NIHSS, GCS, age, sex, race, and prior stroke history. Results: Among 2,486 confirmed AIS patients from 1/1/2015-12/31/2015, 868 were transported by EMS, including 595 (69%) with EMS suspected stroke. Compared to EMS non-suspected strokes, patients with EMS suspected stroke patients were more likely to receive thrombolysis (18% vs 8%; OR 2.67, 95% CI 1.63-4.47) and had faster prehospital transport (30 vs 32 min, p=0.02), ED arrival to CT (27 vs 46 min, p Conclusions: In a large population-based study, EMS stroke identification is associated with a higher rate of and faster thrombolysis. Efforts to increase accuracy of EMS stroke identification is likely to have significant clinical impact by shortening treatment times.

Background: Data from the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) have demonstrated stable or increasing stroke incidence rates in young adults with differences by sex and race, suggesting the need for targeted approaches to stroke prevention in the young. We aimed to describe trends over time in prevalence of stroke risk factors among adults ages 20-54 with stroke by sex and race. Methods: Cases of incident stroke (IS, ICH, SAH) occurring in those 20-54 years old and living in a 5-county area of southern Ohio/northern Kentucky were ascertained during 5 study periods (1993-1994, 1999, 2005, 2010, 2015). All physician-adjudicated inpatient events and a sampling of outpatient events were included, excluding nursing home events. Data on risk factors (hypertension, diabetes, obesity (BMI≥30), and high cholesterol) diagnosed prior to stroke were abstracted from medical records, and prevalence of each risk factor was reported over time in race/sex groups. Trends over time were examined using the Cochran-Armitage test. Results: Over the 5 study periods, 1204 incident strokes were included; 49% were women, 33% were black, and mean age was 46 (SD 7) years. Premorbid hypertension increased over time in Black women (48% in 1993/4 to 76% in 2015, p=0.005) but not in any other race/sex group (all p>0.05). Premorbid high cholesterol increased significantly in all race/sex groups (Figure, all p Conclusions: Among patients aged 20-54 with incident stroke in a large population-based study, the change in the prevalence of hypertension and high cholesterol differed by sex and race, while obesity and diabetes were stable over time in all race/sex groups. Future research is needed to address risk factor control at a population level and to understand the role of undiagnosed pre-stroke risk factors in the young.

Objective: Ischemic stroke (IS) is sexually dimorphic for risk factors, age, heritability, causes, treatment, and outcome. We identified transcriptional correlates with 90-day outcome that differed between male and female IS subjects. Methods: RNA from 72 samples from 2 peripheral blood draws (at ≤3 and 24h post IS onset) was analyzed on Affymetrix U133 Plus 2 microarrays. These represented samples from 36 CLEAR trial IS patients treated with tPA with or without eptifibatide after the first blood sample within 3 hours of stroke onset. Changes in gene expression levels (deltaGE) between 3h and 24h were calculated and the association with percent NIH Stroke Scale (NIHSS) improvement from 3h to 90 days (% Improvement) examined. We used mixed-effects linear regression, including Treatment, Age, Sex, Vascular Risk Factors, 3h NIHSS, % Improvement, and a Sex * % Improvement interaction. Sex differences in association of gene expression with % Improvement were determined by examining the Sex * % Improvement interaction term, p Results: 577 genes correlated differently with % Improvement in IS males and females. These included matrix metalloproteinases (MMPs), which play a major role in BBB dysfunction and outcomes post IS. MMP11 , MMP14 and MM17 correlated with % Improvement in opposite direction in males and females. Inflammatory genes like IL-27 , implicated in infarct volume and stroke outcome, and ABC transporters ( ABCC9 ) also had opposite correlation with % Improvement in males and females. Calmodulin 1 ( CAML1 ) was also sexually dimorphic, and a SNP in CALM1 has been implicated in IS risk and blood coagulation in female IS patients. EIF2 signaling, a major protein synthesis pathway was activated in males (adj. p = 1e-8), while suppressed in females (adj. p value = 1e-9). Protein synthesis and associated unfolded protein response cascade have previously been implicated in stroke outcome. Conclusions: The identified sexually dimorphic gene expression associated with 90-day improvement might relate to sex differences in blood immune and clotting pathways. The findings expand our understanding of the genomic underpinnings associated with stroke outcome and may serve as potential sex-specific treatment targets.

Introduction: Adult women with Turner syndrome (TS) have a high prevalence of diabetes and β-cell dysfunction that increases morbidity and mortality, but it is unknown if there is β-cell dysfunction present in youth with TS. This study aimed to determine the prevalence of β-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity (SI) and insulin secretion. Methods: Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam, and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine β-cell function. Results: Twenty-one TS girls (35%) met criteria for prediabetes. Impaired fasting glucose was present in 18% of girls with TS and 3% HC (p value = 0.02). Impaired glucose tolerance was present in 23% of TS girls and 0% HC (p value p = 0.42). Youth with TS had significant reductions in SI, β-cell responsivity (Φ), and disposition index (DI) compared to HC. These differences remained significant when controlling for body mass index z-score (p values: 0.0006, 0.002, Conclusions: β-Cell dysfunction is present in youth with TS compared to controls. The presence of both reduced insulin secretion and SI suggest a unique TS-related glycemic phenotype. Based on the data from this study, we strongly suggest that providers employ serial OGTT to screen for glucose abnormalities in TS youth.

Linear regression is often used to estimate associations between chemical exposures and neurodevelopment at the mean of the outcome. However, the potential effect of chemicals may be greater among individuals at the ‘tails’ of outcome distributions. Here, we investigated distributional effects on the associations between gestational phthalate exposure and child Autism Spectrum Disorder (ASD)-related behaviors using quantile regression. We harmonized data from the Early Autism Risk Longitudinal Investigation (EARLI) (n = 140) Study, an enriched-risk cohort of mothers who had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study (n = 276), a general population cohort. We measured concentrations of 9 phthalate metabolites in urine samples collected twice during pregnancy. Caregivers reported children’s ASD-related behaviors using the Social Responsiveness Scale (SRS) at age 3–8 years, higher scores indicate more ASD-related behaviors. In EARLI, associations between phthalate concentrations and SRS scores were predominately inverse or null across SRS score quantiles. In HOME, positive associations of mono-n-butyl phthalate, monobenzyl phthalate, mono-isobutyl phthalate, and di-2-ethylhexyl phthalate concentrations with SRS scores increased in strength from the median to 95th percentile of SRS scores. These results suggest associations between phthalate concentrations and SRS scores may be stronger in individuals with higher SRS scores.

We examined the efficacy of a pediatric emergency visit-based screening, brief intervention, and referral to treatment (SBIRT) condition compared to a control condition (Healthy Habits Control, HHC) to help parental smokers quit smoking. We enrolled 750 parental smokers who presented to the pediatric emergency setting with their child into a two-group randomized controlled clinical trial. SBIRT participants received brief cessation coaching, quitting resources, and up to 12-weeks of nicotine replacement therapy (NRT). HHC participants received healthy lifestyle coaching and resources. The primary outcome was point-prevalence tobacco abstinence at six weeks (T1) and six months (T2). The mean (SD) age of parents was 31.8 (7.7) years, and 86.8% were female, 52.7% were Black, and 64.6% had an income of &le, $15,000. Overall abstinence rates were not statistically significant with 4.2% in both groups at T1 and 12.9% and 8.3% in the SBIRT and HHC groups, respectively, at T2. There were statistically significant differences in SBIRT versus HHC participants on the median (IQR) reduction of daily cigarettes smoked at T1 from baseline (&minus, 2 [&minus, 5, 0] versus 0 [&minus, 4, 0], p = 0.0008),at T2 from baseline (&minus, 4 [&minus, 9, &minus, 1] vs. &minus, 5, 0], p = 0.0006), and on the mean (SD) number of quit attempts at T2 from baseline (1.25 (6.5) vs. 0.02 (4.71), p = 0.02). Self-reported quitting rates were higher in SBIRT parents who received NRT (83.3% vs. 50.9%, p = 0.04). The novel use of the pediatric emergency visit to conduct cessation interventions helped parents quit smoking. The near equivalent abstinence rates in both the SBIRT and HHC groups may be due to underlying parental concern about their child&rsquo, s health. Cessation interventions in this setting may result in adult and pediatric public health benefits.

Background and Purpose— The Graeb score is a visual rating scale of intraventricular hemorrhage (IVH) on noncontrast head CT. Little data exist in the hyperacute ( Methods— A retrospective analysis of multicenter prospective intracranial hemorrhage study was performed. oGS and mGS inter-observer agreement and IVH volume correlation on the baseline noncontrast head CT were calculated by intraclass correlation coefficient and Pearson coefficient respectively. Predictors of poor outcome (modified Rankin Scale scores ≥4) at 3 months were identified using a backward stepwise selection multivariable analysis. oGS and mGS performance for modified Rankin Scale scores ≥4 was determined by receiver operating characteristic analysis. Results— One hundred forty-one patients (65±12 years) with median (interquartile range) time to CT of 82.5 (70.3–157.5) minutes were included. IVH was observed in 43 (30%) patients. Inter-observer agreement was excellent for both oGS (intraclass correlation coefficient, 0.90 [95% CI, 0.80–0.95]) and mGS (intraclass correlation coefficient, 0.97 [95% CI, 0.84–0.99]). mGS (R=0.79; P P P =0.02). Models of thresholded oGS and mGS were not different from a model of planimetric baseline intracranial hemorrhage and IVH volume for poor outcome prediction. Area under the curves were 0.70, 0.73, and 0.72, respectively. Conclusions— Excellent correlation for oGS and mGS with IVH volume was seen. Thresholded oGS and mGS are reasonable surrogates for planimetric IVH volume for hyperacute intracranial hemorrhage studies.

Background: We previously reported an increased incidence of stroke in the population with diabetes. This was particularly pronounced in those under 65 years of age. With guidelines now including glycemic monitoring during hospitalization, we examined incidence attributable to diabetes in 2010 and 2015. Methods: Ischemic strokes in the 5-county Greater Cincinnati/Northern Kentucky region were ascertained, then physician verified, at all 15 area hospitals using ICD-9 codes 430 to 436 or ICD10 codes I60 to I68. First ever ischemic strokes in patients aged 20 years and older were included in this analysis. Population age-specific rates of diabetes were estimated using the 2009-2010 and 2015-2016 NHANES databases, then applied to local population numbers, extracted from the US Census Bureau website, to estimate the denominator for calculation of incidence rates. Incidence rates were adjusted by age race and sex, as appropriate, to the 2010 US population. Diabetes was defined as reported in the electronic medical record or glycohemoglobin A1c &gt 6.4% during hospitalization. Results: There were a total of 4141 ischemic strokes; 55% female and 22% black. Stroke rates continue to be substantially higher in those with diagnosed diabetes, than those without diabetes overall and for those less than 65 years in both time periods, as well as those 65 years and older except for the black population in 2010. Racial disparities continue in both the less than 65 and 65 years and older age groups. Stroke rates were higher for Blacks in the less than 65 year age group for those both with and without diabetes; with risk ratios ranging from 1.3 to 2.7. Of note the stroke rate has decreased between 2010 and 2015 for those with diabetes Conclusions: The population with diabetes continues to be at increased risk of stroke, especially in those less than 65 years of age and those of black race.

Introduction: Data from the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) through 2010 showed that over time, stroke incidence rates decreased to a greater extent in men than in women. We aimed to determine whether this difference continued through 2015 and whether the differences are driven by particular age groups. Methods: Within the GCNKSS population of 1.3 million, all incident strokes among residents ≥20 years old were ascertained at all local hospitals during 7/93–6/94 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, standardized to the 2010 U.S. Census. Trends over time by sex were compared (overall and age-stratified); a Bonferroni correction was applied for multiple comparisons. Results: In total over the five study periods, there were 9721 incident strokes (ischemic, ICH, and SAH); 56.4% were women. Incidence of ischemic strokes decreased from 254 (95%CI 236,272) in 1993/4 to 177 (95%CI 164,189) in 2015 among men (p Conclusions: Stroke incidence decreased between the early 1990s and 2015 for both sexes, contrary to previous data on trends through 2010 which demonstrated a significant decrease in men but not women. Temporal changes are being driven by the 65–84 year age group in both men and women, as well as the ≥ 85 age group in men. Future prevention strategies should target young and middle age adults for both sexes as well as those over 85 for women.

Background: Cerebellar lesions reportedly account for 2-7% of acute infarct visits, but this may be an underestimate since prior studies were not population-based or from the modern imaging era. Cerebellar symptoms are also often nonspecific such that increased MRI use might lead to a higher proportion of stroke due to cerebellar lesions. Details about presenting features of cerebellar infarcts and baseline medication use are also not well known. Methods: We used the 2010 Greater Cincinnati/Northern Kentucky Stroke Study. Strokes were identified by screening ICD9 codes 430-436 and physician verification. Infarct location was categorized as isolated cerebellar, mixed cerebellar (cerebellar plus ≥1 other location), or non-cerebellar. Isolated dizziness was defined as dizziness/vertigo without other focal symptoms. Atherosclerotic cardiovascular disease (ASCVD) 10-year risk scores were calculated. Descriptive statistics and multivariable logistic regression were used to compare infarct categories. Results: Isolated cerebellar lesions occurred in 4.6% (90/1940; 95% CI, 3.7%-5.7%) of infarct events. An additional 4% (77/1940; 95%CI, 3.1%-4.9%) were mixed cerebellar infarcts. Mixed cerebellar infarcts had clinical characteristics more similar to non-cerebellar events than to cerebellar events. The multivariable model found an association of isolated cerebellar infarct with low NIHSS (odds ratio [OR] 2.3, 95% CI 1.1-4.8) and any dizziness/vertigo (OR 5.1, 95% CI, 2.4-10.6), but not with isolated dizziness/vertigo, age, or sex. Median ASCVD scores were high in all infarct categories (21, interquartile range [IQR] 9-35 for isolated cerebellar; 32, IQR 15-42 for mixed cerebellar; 31, IQR 16-52 for all others). Both cerebellar and non-cerebellar strokes had a high frequency of baseline antiplatelet or anticoagulant use (52.1% vs 56.2%), whereas baseline statin therapy was less common in isolated cerebellar infarcts (34.1% vs 43.8%). Conclusions: This population-based study during the modern imaging era found that about 5% of stroke cases have isolated cerebellar infarcts and nearly 9% have any cerebellar infarct. Both cerebellar and non-cerebellar presentations have high baseline vascular risk and antiplatelet/anticoagulant use.

Background. Exercise intensity can influence functional recovery after stroke, but the mechanisms remain poorly understood. Objective. In chronic stroke, an intensity-dependent increase in circulating brain-derived neurotrophic factor (BDNF) was previously found during vigorous exercise. Using the same serum samples, this study tested acute effects of exercise intensity on other circulating molecules related to neuroplasticity, including vascular-endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF1), and cortisol, with some updated analyses involving BDNF. Methods. Using a repeated-measures design, 16 participants with chronic stroke performed 3 exercise protocols in random order: treadmill high-intensity interval training (HIT-treadmill), seated-stepper HIT (HIT-stepper), and treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum molecular changes were compared between protocols. Mediation and effect modification analyses were also performed. Results. VEGF significantly increased during HIT-treadmill, IGF1 increased during both HIT protocols and cortisol nonsignificantly decreased during each protocol. VEGF response was significantly greater for HIT-treadmill versus MCT-treadmill when controlling for baseline. Blood lactate positively mediated the effect of HIT on BDNF and cortisol. Peak treadmill speed positively mediated effects on BDNF and VEGF. Participants with comfortable gait speed ≥0.4 m/s had significantly lower VEGF and higher IGF1 responses, with a lower cortisol response during MCT-treadmill. Conclusions. BDNF and VEGF are promising serum molecules to include in future studies testing intensity-dependent mechanisms of exercise on neurologic recovery. Fast training speed and anaerobic intensity appear to be critical ingredients for eliciting these molecular responses. Serum molecular response differences between gait speed subgroups provide a possible biologic basis for previously observed differences in training responsiveness.

Obesity is identified as a major global health problem. Along with measuring body mass index (BMI), the most common metric for defining weight status, health related quality of life (HRQol) has been accepted as a routine method to evaluate how body weight may be impacted by psychosocial factors. The objective of the current study is to characterize the joint association of change in longitudinal BMI and HRQol following metabolic and bariatric surgery and to examine the correlation between these two outcomes measured concurrently over time. We identified the optimal modeling strategy by comparing four models, all of which involved the covariance structures appropriate for correlated outcomes, BMI and HRQol in a repeated measures analysis. The bivariate random effects models performed better than the univariate random effects models. Moreover, bivariate models with composite covariate structures had better model fit compared to the bivariate random slope models. The bivariate models with composite covariate structures reflected that changes in HRQol (and BMI) were most significant during the first 6 months, a clinically useful window to monitor changes in post-operative HRQol and BMI, and if there might need to be additional interventions or at least, closer monitoring.

Background Breast milk represents the optimal substrate for all infants, including those with a cleft palate for whom growth may be compromised. Objectives Frequency of breast milk feeding at the breast and per feeder (bottle, cup, enteral tube) in infants with cleft palate was determined and compared with rates reported by the Centers for Disease Control and Prevention. A secondary aim was to review growth status of the infants. Design This study represents a 5-year retrospective review using the electronic medical record. Participants and setting Patients were ≤12 months old at the time of the initial, presurgical encounter after a diagnosis of cleft palate had been made and were treated at one of two pediatric cleft palate and craniofacial centers in Ohio between September 30, 2010, and September 30, 2015. Main outcome measures Outcomes measured were breast milk use, reported by mothers and documented in patients' electronic medical records, chronological body weight, as well as weight for length and weight-for-age z scores and percentiles. Statistical analyses performed Descriptive statistics included median with interquartile range and frequency with percentages. World Health Organization z scores were estimated using the Centers for Disease Control and Prevention programs for weight, weight for length, and weight for age at first visit. Comparisons of infants treated at the two hospitals were done using the Wilcoxon rank-sum test or the χ2 test. Results Breast milk consumption (26 infants were breastfed and 84 received human breast milk administered with a device) was 29.5%, markedly below the 2016 Centers for Disease Control and Prevention national statistics for ever receiving breast milk (81%). Anthropometric findings included z scores of −0.95 and −0.42 for weight for age and weight for length, respectively. Conclusions Infants with cleft palate were seldom breastfed, nor was breast milk frequently used. In addition, median weight-for-age and weight-for-length z scores suggest that growth of infants with cleft palate was below normative standards.

Context Pregnancy-associated plasma protein A2 (PAPPA2) is a protease that cleaves IGF-binding protein (IGFBP)-3 and IGFBP-5, liberating free IGF-I. Five patients from two families with genetic mutations in PAPPA2 presented with growth retardation, elevated total IGF-I, and IGFBP-3 but decreased free IGF-I. Objective To determine whether plasma transfusion or recombinant human (rh)PAPPA2 could increase free IGF-I in patients with PAPPA2 deficiency or idiopathic short stature (ISS). Design Single patient interventional study combined with in vitro experimentation. Setting Academic medical center. Patients Three siblings with PAPPA2 deficiency and four patients with ISS. Interventions An adult female with PAPPA2 deficiency received a 20 mL/kg plasma transfusion. PAPPA2, intact IGFBP-3, and free and total IGF-I levels were monitored during 2 weeks. rhPAPPA2 was added to serum from patients with PAPPA2 deficiency and ISS in vitro for 4 hours. Intact IGFBP-3 and free IGF-I levels were assayed via ELISA. Main Outcome Measures Free IGF-I concentrations. Results Plasma transfusion resulted in a 2.5-fold increase of free IGF-I levels on day 1 posttransfusion with a return to baseline during a 2-week period. In vitro studies demonstrated a dose-dependent increase in free IGF-I and decrease in intact IGFBP-3 after the addition of rhPAPPA2. The increase in free IGF-I was more pronounced in patients with PAPPA2 deficiency compared with those with ISS. Conclusions PAPPA2 plays a key role in regulation of IGF-I bioavailability. rhPAPPA2 is a promising therapy to increase free IGF-I levels both in patients with PAPPA2 deficiency as well as in patients with ISS., PAPPA2 was given to a female with PAPPA2 deficiency via plasma transfusion, and recombinant PAPPA2 was added to serum from patients with PAPPA2 deficiency or ISS, resulting in increased free IGF-I.

Background and Purpose— Computed tomographic angiography and conventional angiography provide timely vascular anatomic information in patients with stroke. However, iodinated contrast dye may cause acute kidney injury (AKI). Within a large, biracial population, we examined in-hospital incidence of new or worsening kidney disease in patients with stroke and its association with administration of intravenous dye. Methods— All adult residents of the Greater Cincinnati/Northern Kentucky region with acute ischemic stroke or intracerebral hemorrhage who presented to an emergency department in 2010 were included. Prevalence of unsuspected kidney disease at the time of emergency department presentation and the incidence of AKI after admission in 2 groups of patients—those who did and those who did not receive intravenous dye—were determined. Results— In 2010, 2299 patients met inclusion criteria (89% ischemic stroke and 11% intracerebral hemorrhage); mean age 69 years (SD 15), 22% black, and 54% women. Among these patients, 37% had kidney disease at baseline, including 22% (516/2299) in whom this was unsuspected. Two percent (2%; 15/853) of patients with baseline kidney disease developed AKI during the hospital stay. Of those with no baseline kidney disease, 1% (14/14 467) developed AKI. There was no association between dye administration and new or worsening kidney disease. Conclusions— Although 22% of patients in the Greater Cincinnati/Northern Kentucky stroke population had unsuspected kidney disease, the incidence of new or worsening kidney disease was low, and AKI was not associated with dye administration. These findings confirm single-center reports that the risk of severe renal complications after contrast dye is small.

Best practice recommendations indicate that aerobic exercise (AEX) should be incorporated into stroke rehabilitation. However, this may be challenging in clinical settings. The purpose of this study was to assess physical therapist (PT) AEX prescription for patients with stroke, including AEX utilization, barriers to AEX prescription, dosing parameters, and safety considerations.A cross-sectional Web-based survey study was conducted. Physical therapists with valid e-mail addresses on file with the state boards of Florida, New Jersey, Ohio, Texas, and Wyoming were eligible to participate. Survey invitations were e-mailed to all licensed PT in these states. Analysis focused on respondents who were currently involved with clinical stroke rehabilitation in common practice settings.Results from 568 respondents were analyzed. Most respondents (88%) agreed that AEX should be incorporated into stroke rehabilitation, but 84% perceived at least one barrier. Median prescribed AEX volume varied between practice settings from 20- to 30-minute AEX sessions, 3 to 5 days per week for 2 to 8 weeks. Prescribed intensity was most commonly light or moderate; intensity was determined by the general response to AEX and patient feedback. Only 2% of respondents reported that the majority of their patients with stroke had stress tests.Most US PTs appear to recognize the importance of AEX for persons poststroke, but clinical implementation can be challenging. Future studies and consensus are needed to clarify best practices and to develop implementation interventions to optimize AEX utilization in stroke rehabilitation.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A167).

The purpose of this study was to assess safety via electrocardiographic (ECG), blood pressure (BP), heart rate (HR), and orthopedic responses to 3 different high-intensity interval training (HIIT) protocols in persons with stroke. Eighteen participants (10 male; 61.9 + 8.3 years of age; 5.8 + 4.2 years poststroke) completed a symptom-limited graded exercise test (GXT) with ECG monitoring to screen for eligibility and determine HR peak. The 3 HIIT protocols involved repeated 30 s bursts of treadmill walking at maximum speed alternated with rest periods of 30 s (P30), 1 min (P60), or 2 min (P120). Sessions were performed in random order and included 5 min warm up, 20 min HIIT, and 5 min cool down. Variables measured included ECG activity, BP, HR, signs and symptoms of cardiovascular intolerance, and orthopedic concerns. Generalized linear mixed models and Tukey–Kramer adjustment were used to compare protocols using p < 0.05. No signs or symptoms of cardiovascular intolerance, significant arrhythmias, ST segment changes, or orthopedic responses resulted in early termination of any HIIT session. HIIT elicited HRs in excess of 88% of measured HRpeak including 6 (P30), 8 (P60), and 2 (P120) participants eliciting a HR response above their GXT HRpeak. Both maximum BP and HR were significantly higher in P30 and P60 relative to P120. Preliminary data indicate that persons with chronic stroke who have been prescreened with an ECG stress test, a symptom-limited GXT, and a harness for fall protection may safely participate in HIIT, generating substantially higher HRs than what is seen in traditional moderate intensity training.

Insulin-like growth factor I (IGF-I) is one of the essential hormonal mediators of human growth. Circulating IGF-I exists in a ternary complex bound to the acid-labile subunit (ALS) and an IGF binding protein, predominantly IGFBP-3. Pregnancy Associated Plasma Protein-A2 (PAPP-A2), which cleaves intact IGFBP-3, liberates IGF-I from the ternary complex to interact with cell surface receptors. Genome-wide association studies have linked PAPPA2 to adult stature, and mutations in PAPPA2 cause short stature with decreased IGF-I bioavailability. As little is known about PAPP-A2 concentrations throughout childhood and its association with IGF-I bioavailability, we evaluated normal serum concentrations of free IGF-I, intact IGFBP-3, and PAPP-A2 throughout childhood and their relationship with anthropometry. We assessed serum samples from 838 individuals (Age: 3-18, Male: 48%, Caucasian: 83%) who participated in the Cincinnati Genomic Control Cohort, a population-based study of generally healthy children. Patients on medications known to affect growth or with significant medical comorbidities were excluded. Subjects were evaluated at a single visit. Height and weight were measured and a blood sample was drawn. Serum samples were aliquoted and stored at −80 ° C without thawing until the current assays were performed. Total and free IGF-I, total and intact IGFBP-3 and PAPP-A2 were measured using ELISA kits developed by Ansh Laboratories. Age-specific reference interval curves were generated by sex. Correlation and regression analyses were used to examine relationships among analytes and association between each analyte and age, sex, race, height, and BMI. Statistical analyses were performed using SAS®, version 9.4. Free IGF-I increased with age. Serum PAPP-A2 consistently decreased throughout childhood. Serum intact IGFBP-3 increased from early childhood into adolescence with a more marked rise than total IGFBP-3. In multiple regression analysis, height Z-score was positively associated with free and total IGF-I (P=0.01; P

Introduction: We previously reported that the incidence of stroke was decreasing for whites but stable for blacks from 1993/94 to 2005. We sought to describe recent temporal trends and racial disparities in stroke incidence within our large, bi-racial population, by including 2010 and preliminary data from 2015. Methods: The Greater Cincinnati/Northern Kentucky region includes two southern Ohio and three Northern Kentucky counties on the Ohio River, a population of 1.3 million representative of the US population in terms of sociodemographics and percent black race. Our study ascertained all hospitalized strokes that occurred in the population between 7/1/93 and 6/30/94 and in calendar years 1999, 2005, 2010 and 2015. For 2015, nursing review of medical records is complete but physician review is not; thus 2015 rates are preliminary. The denominator for the calculation of incidence rates (in those aged ≥20 years) was estimated from the U.S. Census Bureau website (www.census.gov). The 95% confidence intervals (CI) for the incidence rates were calculated assuming a Poisson distribution. Rates are age, sex, and race adjusted, as appropriate, and standardized to the 2010 U.S. population. Results: First-ever stroke incidence rates stratified by subtype, race, and study period are presented in the Table. We project that stroke incidence did not significantly change in 2015 vs. 2010 for either blacks or whites, regardless of stroke subtype. Blacks have a substantially higher incidence of stroke compared with whites in all study periods, without significant change in disparity over time. Discussion: In contrast to the significant decline in stroke incidence among whites from 1993-94 to 2005, we did not observe a statistically significant decrease in 2010 and 2015. This may be due to true stabilization of rates over time, or less statistical power to detect smaller declines. The substantial black/white racial disparity in stroke incidence has not changed over time.

Introduction: Previous studies have shown biases in screening for toxicologic substances among stroke patients but have limited generalizability. Our objective was to investigate predictors of the use of drug screens among stroke patients in a large population based study. Methods: The Greater Cincinnati Northern Kentucky Stroke Study is a population-based study of stroke cases ascertained from a biracial population of 1.3 million people in a 5-county region of southern Ohio/northern Kentucky. All hospital ascertained cases of stroke (ischemic (IS), transient ischemic attack (TIA), hemorrhagic (ICH), subarachnoid hemorrhage (SAH)), occurring during calendar year 2015 were included. Trained study nurses abstracted data on whether a drug screen was ordered (between emergency department (ED) presentation and hospital discharge). Screening tests for alcohol were not included. Multivariable logistic regression was used to identify predictors of use of a drug screen. Potential predictors were patient sex, age, race, select comorbidities, smoking status, stroke severity (NIHSS), treatment location and stroke type. Results: Of 3865 stroke cases (53.8% women, 20.8% black, mean age 69.7(14.8) years), 12.0% had a drug screen performed. Adjusted, black race (aOR 1.93 95%CI 1.52-2.44), current smoking (aOR 1.97 95%CI 1.58-2.47), higher NIHSS (aOR 1.22 95%CI 1.15-1.28 per 5 unit increase) and being treated in an academic ED (aOR 2.04, 95%CI 1.62-2.55) increased the likelihood of a drug screen, while female gender (aOR 0.75 95%CI 0.60-0.93) and older age (aOR 0.61 per 10 years, 95%CI 0.56-0.66) decreased the likelihood. Conclusions: In a large population based study of stroke patients, drug screens were more likely to be ordered in men, blacks, smokers, younger patients, and those seen in academic EDs. It is unknown whether these trends are similar among hospitalized patients with other diagnoses. Additionally, current evidence suggests that such differential testing may lead to missed counselling opportunities in those not tested as well as lower likelihood of thrombolytic treatment in those who are tested. Future research should investigate the yield of such drug screens and explore whether guidelines in ordering drug tests could help to avoid testing biases.

Objective: To update trends on documented substance abuse among young adults (18-54 years old) with stroke within the Greater Cincinnati/Northern Kentucky Stroke Study population, to include preliminary results from 2015. Background: Substance abuse is associated with stroke. In our population, we previously reported increases in overall substance abuse, smoking history, and use of alcohol or drugs >Design/Methods: Using ICD-9 discharge codes 430-436, potential acute stroke events are identified among 18- to 55-year-old residents of the 5 county study region. Five one-year study periods are included (7/93-6/94, 1999, 2005, 2010, 2015). Study nurses abstract all events which then undergo physician review. We searched for trends in smoking history, illicit drug use, heavy alcohol consumption, overall substance abuse (current smoking, alcohol, and illicit drug), and urine/blood test positive for alcohol or illicit drugs at presentation. Results: There were 2220 stroke events (75 % ischemic). Sex and age distribution remained stable; however, percent black increased from 35% to 46% between 1993/94 and 2015, as did the proportion of ischemic strokes (74% to 77%). Current smoking and alcohol use remained stable while illicit drug use increased significantly overall and within the age subgroups of 18-34 years and 35-54 years (see table). Conclusions: Illicit drug use continues to increase among young adults with stroke. Even though the possibility of testing bias needs to be explored further, our reported results are likely an under estimation of true rates as there are no readily available tests for new designer drugs which have become more available since the early 2000’s. Future analysis will also focus on the relationship between our findings and the U.S. opioid epidemic.

In the attention-deficit hyperactivity disorder (ADHD) study, children are prescribed different stimulant medications. The height measurements are recorded longitudinally along with the medication time. Differences among the patients are captured by the parameters suggested the Superimposition by Translation and Rotation (SITAR) model using three subject-specific parameters to estimate their deviation from the mean growth curve. In this paper, we generalize the SITAR model in a Bayesian way with time-invariant covariates. The time-invariant model allows us to predict latent growth factors. Since patients suffer from a common disease, they usually exhibit a similar pattern, and it is natural to build a nonlinear model that is shaped invariant. The model is semi-parametric, where the population time curve is modeled with a natural cubic spline. The original shape invariant growth curve model, motivated by epidemiological research on the evolution of pubertal heights over time, fits the underlying shape function for height over age and estimates subject-specific deviations from this curve in terms of size, tempo, and velocity using maximum likelihood. The usefulness of the model is illustrated in the attention deficit hyperactivity disorder (ADHD) study. Further, we demonstrated the effect of stimulant medications on pubertal growth by gender.

Prenatal exposure to organophosphate pesticides, which is ubiquitous, may be detrimental to neurological development. We examined 327 mother/infant pairs in Cincinnati, Ohio, between 2003 and 2006 to determine associations between prenatal exposure to organophosphate pesticides and neurodevelopment. Twice during pregnancy urinary concentrations of 6 common dialkylphosphates, nonspecific metabolites of organophosphate pesticides, were measured. Aggregate concentrations of diethylphosphates, dimethylphosphates, and total dialkylphosphates were calculated. Bayley Scales of Infant Development, Second Edition-Mental and Psychomotor Developmental indices were administered at ages 1, 2, and 3 years, the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, at age 4, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at age 5. Mothers with higher urinary total dialkylphosphate concentrations reported higher levels of socioeconomic status and increased fresh fruit and vegetable intake. We found no associations between prenatal exposure to organophosphate pesticides and cognition at 1–5 years of age. In our cohort, exposure to organophosphate pesticides during pregnancy was not associated with cognition during early childhood. It is possible that a higher socioeconomic status and healthier diet may protect the fetus from potential adverse associations with gestational organophosphate pesticide exposure, or that dietary exposure to the metabolites is innocuous and not an ideal measure of exposure to the parent compound.

Background: After stroke, aerobic deconditioning can have a profound impact on daily activities. This is usually measured by the peak oxygen consumption rate achieved during exercise testing (VO2-peak). However, VO2-peak may be distorted by motor function. The oxygen uptake efficiency slope (OUES) and VO2 at the ventilatory threshold (VO2-VT) could more specifically assess aerobic capacity after stroke, but this has not been tested. Objectives: To assess the differential influence of motor function on three measures of aerobic capacity (VO2-peak, OUES, and VO2-VT) and to evaluate the inter-rater reliability of VO2-VT determination post-stroke. Methods: Among 59 persons with chronic stroke, cross-sectional correlations with motor function (comfortable gait speed [CGS] and lower extremity Fugl-Meyer [LEFM]) were compared between the different aerobic capacity measures, after adjustment for covariates, in order to isolate any distorting effect of motor function. Reliability of VO2-VT determination between three raters was assessed with intra-class correlation (ICC). Results: CGS was moderately correlated with VO2-peak (r = 0.52, p r = 0.41, p = 0.002) and VO2-VT (r = 0.37, p = 0.01). LEFM was weakly correlated with VO2-peak (r = 0.26, p = 0.055) and very weakly correlated with OUES (r = 0.19, p = 0.17) and VO2-VT (r = 0.14, p = 0.31). Compared to VO2-peak, VO2-VT was significantly less correlated with CGS (r difference = −0.16, p = 0.02). Inter-rater reliability of VO2-VT determination was high (ICC: 0.93, 95% CI: 0.89–0.96). Conclusions: Motor dysfunction appears to artificially lower measured aerobic capacity. VO2-VT seemed to be less distorted than VO2-peak and had good inter-rater reliability, so it may provide more specific assessment of aerobic capacity post-stroke.

BACKGROUND: Hospital discharge is stressful for children and families. Poor transitional care is linked to unplanned health care reuse. We evaluated the effects of a pediatric transition intervention, specifically a single nurse home visit, on postdischarge outcomes in a randomized controlled trial. METHODS: We randomly assigned 1500 children hospitalized on hospital medicine, neurology services, or neurosurgery services to receive either a single postdischarge nurse-led home visit or no visit. We excluded children discharged with skilled home nursing services. Primary outcomes included 30-day unplanned, urgent health care reuse (composite measure of unplanned readmission, emergency department, or urgent care visit). Secondary outcomes, measured at 14 days, included postdischarge parental coping, number of days until parent-reported return to normal routine, and number of “red flags” or clinical warning signs a parent or caregiver could recall. RESULTS: The 30-day reuse rate was 17.8% in the intervention group and 14.0% in the control group. In the intention-to-treat analysis, children randomly assigned to the intervention group had higher odds of 30-day health care use (odds ratio: 1.33; 95% confidence interval: 1.003–1.76). In the per protocol analysis, there were no differences in 30-day health care use (odds ratio: 1.14; confidence interval: 0.84–1.55). Postdischarge coping scores and number of days until returning to a normal routine were similar between groups. Parents in the intervention group recalled more red flags at 14 days (mean: 1.9 vs 1.6; P < .01). CONCLUSIONS: Children randomly assigned to the intervention had higher rates of 30-day postdischarge unplanned health care reuse. Parents in the intervention group recalled more clinical warning signs 2 weeks after discharge.

BACKGROUND AND OBJECTIVES: Iodine is an essential trace element for maintenance of normal thyroid function. Normal thyroid function is a prerequisite for neurocognitive development and growth in children. In the United States, iodine is not routinely added as a trace element in parenteral nutrition (PN). Our objective was to determine the prevalence of iodine deficiency and hypothyroidism in children on chronic PN. METHODS: This was a cross-sectional study of children 6 months at a tertiary children’s hospital. Primary outcomes were spot urine iodine concentration (UIC), serum thyrotropin, and free thyroxine levels. RESULTS: Twenty-seven patients were identified (74% male). The median age at screening was 48 months (range: 7–213 months). The median duration on PN was 27 months (range: 11–77 months). Seventeen out of 20 patients (85%) were iodine deficient (spot UIC CONCLUSIONS: Children on chronic PN are at risk for developing iodine deficiency and resultant hypothyroidism; hence, these children should be screened for these outcomes. Further studies are needed to define the temporal onset of iodine deficiency and timing to thyroid dysfunction related to PN.