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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/m2, 79% met MetS criteria pre-urgery. MetS-z (1.5) and SAD (32cm) were correlated (r = 0.6, P <.0001) presurgery, and both improved significantly at 6 months, 1, and 5 years postsurgery, remaining highly correlated at each timepoint. SAD predicted MetS-z (β = 0.118; 95% CI, 0.109, 0.127) after adjustment for age, visit, surgery type, and caregiver education. Abdominal 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. • Metabolic syndrome (MetS) is prevalent in adolescents undergoing bariatric surgery • Abdominal obesity is strongly associated with MetS risk in this population • Major reductions in MetS risk and abdominal obesity persist 5 years postsurgery • Interventions targeting abdominal obesity may reduce MetS risk in youth [ABSTRACT FROM AUTHOR]

Background and Aims: 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).Methods and Results: 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); P <0.0001] 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Adolescent obesity is associated with significant co-morbidities, 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. The aim of this study was to evaluate QOL and the effect of these symptoms on QOL after bariatric surgery. Five academic centers that perform adolescent MBS in the United States. We prospectively studied 228 adolescents undergoing MBS using the Teen-Longitudinal Assessment of Bariatric Surgery cohort. GIS 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. Adjusting for body mass index 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 <.0001). The mental component score did not significantly change over time. The SF-36 domains that showed the biggest increase after surgery were physical functioning, physical role functioning, and general health. The SF-36 PCS decreased significantly over time post surgery in those with GIS of reflux, nausea, and diarrhea but remained higher than baseline SF-36 PCS. There was no statistically significant change in mental component score or impact of weight on quality of life-KIDS scores in those with or without GIS. QOL, specifically the SF-36 PCS, increases after MBS. Reflux symptoms, nausea, and diarrhea reduce the degree of improvement in QOL in adolescents after MBS. Patients should be monitored and treated for these symptoms to address this decreased QOL. [ABSTRACT FROM AUTHOR]

Objective: Previously we reported that ischemic stroke incidence is declining over time for men but not women. We sought to describe temporal trends of sex differences in incidence of transient ischemic attack (TIA) within the same large, biracial population. Methods: Among the population of 1.3 million in the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) region, TIAs among area residents (≥20 years old) were identified at all local hospitals. Out of hospital cases were ascertained using a sampling scheme. First-ever cases and first within each study period for a patient was included in incidence rates. All cases were physician-adjudicated. Incidence rates (during July 93-June 94 and calendar years 1999, 2005, and 2010) were calculated using the age-, race-, and sex-specific number of TIAs divided by the GCNKSS population in that group; rates were standardized to the 2010 U.S. population. t Tests with Bonferroni correction were used to compare rates over time. Results: There were a total of 4746 TIA events; 53% were female, and 12% were black. In males, incidence decreased from 153 (95% confidence interval [CI] 139-167) per 100,000 in 1993/4 to 117 (95% CI 107-128) in 2010 (P <.05 for trend test) but was similar over time among females (107 (95% CI 97-116) to 102 (95%CI 94-111), P >.05). Conclusions: Within the GCNKSS population, TIA incidence decreased significantly over time in males but not females, data which parallels trends in ischemic stroke in the GCNKSS over the same time period. Future research is needed to determine if these sex differences in incidence over time continue past 2010. [ABSTRACT FROM AUTHOR]

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. 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. 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 < 0.0001) greater odds of GERS compared to RYGB. 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. ClinicalTrials.gov , Identifier: NCT00474318 , https://clinicaltrials.gov/ct2/show/NCT00474318?term=Teen-LABS&rank=1. Treatment Study. Level II. [ABSTRACT FROM AUTHOR]

Purpose We investigated the association between tobacco smoke exposure (TSE) as measured by serum cotinine and lipoprotein cholesterols and adiposity in adolescents. Methods We performed a secondary analysis of 1999–2012 National Health and Nutrition Examination Survey data including participants 12–19 years old. We examined TSE: unexposed (<.05 ng/mL), passively exposed (.05–2.99 ng/mL), and actively exposed (≥3 ng/mL); lipid profiles: total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglycerides; and adiposity: body mass index z -score (BMIZ), waist circumference (WC), and waist-to-height ratio (WHtR). Covariates were age, sex, race/ethnicity, income, diet, and physical activity. Multiple regression models were used to assess the association between TSE and lipid profile variables separately, and then TSE and adiposity measures separately, adjusting for covariates. We performed logistic regression to examine the association of TSE with body mass index and WHtR classifications. Results Of the 11,550 participants, 41.7% were unexposed to tobacco smoke, 40.5% were passively exposed, and 17.8% were actively exposed. Compared with unexposed, participants with active TSE had lower total cholesterol, lower HDL-C, and higher triglycerides; higher BMIZ, higher WC, and higher WHtR; participants with passive TSE had lower HDL-C, higher total cholesterol, and higher LDL-C; higher BMIZ, higher WC, and higher WHtR. Participants actively exposed were at increased odds of being obese or WHtR ≥.65, and those passively exposed were at increased odds of being overweight, obese, or WHtR ≥.65. Conclusions Active TSE and passive TSE are differentially associated with factors within the lipid profile and adiposity, independent of covariates. TSE prevention efforts should start as early as childhood and continue throughout adolescence and adulthood. [ABSTRACT FROM AUTHOR]

Purpose The progression of β-cell function in newly diagnosed adolescents with type 2 diabetes mellitus (T2DM) is not well documented. We hypothesized that at the time of diagnosis with T2DM, adolescents would have impaired β-cell function as demonstrated by the disposition index (calculated as: insulin secretion adjusted for insulin sensitivity), and this would be followed by a rapid decline of function despite standard medical management. Methods Thirty-nine adolescents with recently diagnosed T2DM and 32 obese adolescent controls with normal glucose tolerance had acute insulin response to glucose, homeostatic model assessment of insulin resistance, and disposition index measured serially over 2 years. Results In the adolescent T2DM group, fasting glucose increased over 2 years ( p = .04), while DI was impaired at baseline and showed an overall relative decline of 25% per year. The mean Hemoglobin A 1c remained below 8% (64 mmol/mol). Differences were observed between the T2DM and control adolescents in the way DI changed over time ( p = .02). Conclusions β-cell function in adolescents with recently diagnosed T2DM was impaired with no improvement of β-cell function over the 2 years of study despite stable Hemoglobin A 1c , body mass index markers of insulin sensitivity, and standard treatment of hyperglycemia. [ABSTRACT FROM AUTHOR]

The sport of soccer is the fastest growing and most popular sport worldwide. With this growth and popularity, attention needs to be given to this athletic population. Sports related concussions is a topic that has gained attention both in the media and by governmental organizations, with growing initiatives in diagnosis, prevention and treatment. The act of soccer heading is thought to contribute to increased concussion incidence. Current evidence reveals that within the high school soccer athletic population, female athletes incur a higher concussion rate than males. This is often attributed to many things including differing cervical spinal musculature, skull thickness, etc., but a definitive reason has not yet been found. Other behaviors, such as field awareness and eye discipline™ on the field of play, may also be contributing factors that result in females incurring a greater concussion rate than males. For the purposes of this paper we define eye discipline™ as the ability to keep the eyes engaged in sporting activity with high risk potential. We present our hypothesis that high school female soccer players are more likely to have their eyes closed when in position for heading the ball as compared to high school male soccer players and this lack of visual awareness may increase the risk of concussion. Should these differences be substantiated between males and females, it may initiate and promote discussion of the need for vision training in the high school athletic setting. As a tool for injury prevention, vision training may improve specific visual parameters improving athletes' abilities to process the field of play and prepare for or avoid injury causing situations. Through ocular motor and visual conditioning, an athlete may become more eye disciplined™, and more likely to have their eyes open during heading of the ball, and more likely to avoid concussions. [ABSTRACT FROM AUTHOR]

Introduction: Despite children spending long hours in child care centers, it is unknown what center characteristics are associated with children's moderate to vigorous physical activity (MVPA) at the center and over the 24-hour day.Methods: Mixed model ANOVA evaluated associations between 23 center characteristics (e.g., policies, facilities, practices, and staff training) and time in MVPA, measured with accelerometers, at the child care center and over the 24-hour day among 388 preschoolers from 30 randomly selected child care centers in Cincinnati, Ohio. Data collection occurred from November 2009 through January 2011; data analyses occurred in 2012-2014.Results: Ninety percent of centers reported scheduling two or more outdoor sessions daily, yet only 40% of children had two or more outdoor sessions; 32% had no time outdoors. Eighty-three percent of centers reported scheduling ≥60 minutes outdoors; 28% of children experienced this during observation. Children spent a mean (SE) of 2.0 (0.06) minutes/hour in MVPA. Children with ≥60 minutes outdoor time had 0.6 minutes/hour more MVPA in child care (p=0.001), and 0.5 minutes/hour over the 24-hour day (p=0.001) than those who did not. Presence of an indoor play space, large outdoor playground, portable or fixed play equipment, staff PA training, weather and clothing policies, and TV/computer use were not related to children's MVPA.Conclusions: Outdoor time occurred less frequently than scheduled. Children with ≥60 minutes of outdoor time at the center were more active than children without. Centers may increase preschoolers' PA by adhering to the scheduled ≥60 minutes of outdoor time daily. [ABSTRACT FROM AUTHOR]

Background and Purpose: Antithrombotic medications are effective for ischemic stroke prevention, but stoppage of these medications is associated with an increased risk of thromboembolism. The frequency of antithrombotic withdrawal in the general population is unknown.Methods: We conducted a random phone sample of 2036 households in the Greater Cincinnati metropolitan area, representative of the stroke population by age, sex, and race, to determine the frequency of antithrombotic medication use and stoppage by physicians for medically indicated procedures.Results: Sixty-two percent of survey respondents reported that they were on an antithrombotic medication. Ten percent of participants reported that they had stopped taking their medication within the past 60 days for a medically indicated intervention. Of those who stopped taking the medication, it was more common for persons taking an anticoagulant to stop their medication (20%) than those taking an antiplatelet agent (9%). Colonoscopies and orthopedic surgeries were the most common reasons for withdrawal of antiplatelet agents, whereas orthopedic and vascular surgeries were the most common reason for withdrawal of anticoagulants.Conclusions: Recommended discontinuation of antithrombotic medication for surgical or diagnostic procedures is common practice for persons in the community representative of a stroke population. Because stoppage of these medications is associated with an increased risk of thromboembolic stroke, further clinical trials are needed to determine best management practices in this setting. [ABSTRACT FROM AUTHOR]

Background: A high proportion of patients excluded from recombinant tissue plasminogen activator (rt-PA) treatment because of rapid improvement occurring before treatment decision had incomplete recovery. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trials dataset allows for systematic analyses of very early postrandomization improvement (VEPRIM) in stroke severity as a National Institutes of Health Stroke Scale (NIHSS) score was available for all subjects enrolled in the study at baseline (NIHSSB) and at 2 hours after randomization (NIHSS2H). We explored various definitions of VEPRIM to characterize predictive values for clinical outcomes.Methods: Post hoc analyses of the NINDS rt-PA Stroke Trials were conducted. VEPRIM was defined as the difference between the NIHSSB and the NIHSS2H scores using 3 approaches: raw, percent, and normalized change. We assessed the association between VEPRIM and 3-month favorable outcome (mRS score of 0-1), symptomatic intracerebral hemorrhage (sICH), and death.Results: In the 624 subjects, every VEPRIM definition was independently associated with an increased probability of favorable outcome: for each unit of change within the VEPRIM definitions, there were 2%-24% (all P < .05) relative increased probability of favorable outcome, 2%-15% (all P < .05) decreased likelihood of death, and 2%-13% (all P < .05) decreased likelihood of sICH. Adjusting for NIHSSB and prestroke mRS scores, there was a significant rt-PA treatment effect for improvement seen for all 3 VEPRIM definitions.Conclusions: VEPRIM predicted favorable outcomes independent of definition and treatment arm. Patients with VEPRIM by any definition, while doing better than patients without VEPRIM, also derived increased clinical benefit when treated with rt-PA compared to placebo. Even with VEPRIM, a substantial percentage of patients had unfavorable outcomes. [ABSTRACT FROM AUTHOR]

Background Studies examining the effects of low-level gestational methylmercury exposure from fish consumption on infant neurobehavioral outcomes in the offspring are limited and inconclusive. Our objective was to examine the effects of low-level gestational exposure to methylmercury on neurobehavioral outcomes in early infancy. Methods We assessed neurobehavior of 344 infants at 5-weeks using the NICU Network Neurobehavioral Scale (NNNS). Gestational mercury exposure was measured as whole blood total mercury (WBTHg) in maternal and cord blood. We collected fish consumption information and estimated polyunsaturated fatty acid (PUFA) intake. We examined the association between gestational mercury exposure and NNNS scales using regression, adjusting for covariates. Results Geometric mean of maternal and cord WBTHg were 0.64 and 0.72 μg/L, respectively. Most mothers (84%) reported eating fish during pregnancy. Infants with higher prenatal mercury exposure showed increased asymmetric reflexes among girls (p = 0.04 for maternal WBTHg and p = 0.03 for cord WBTHg), less need for special handling during the assessment (p = 0.03 for cord WBTHg) and a trend of better attention (p = 0.054 for both maternal WBTHg and cord WBTHg). Similarly, infants born to mothers with higher fish consumption or estimated PUFA intake also had increased asymmetric reflexes and less need for special handling. In models simultaneously adjusted for WBTHg and fish consumption (or PUFA intake), the previously observed WBTHg effects were attenuated; and higher fish consumption (or PUFA intake) was significantly associated with less need for special handling. Conclusions In a cohort with low level mercury exposure and reporting low fish consumption, we found minimal evidence of mercury associated detrimental effects on neurobehavioral outcomes during early infancy. Higher prenatal mercury exposure was associated with more frequent asymmetric reflexes in girls. In contrast, infants with higher prenatal mercury exposure and those whose mothers consumed more fish had better attention and needed less special handling, which likely reflect the beneficial nutritional effects of fish consumption. [ABSTRACT FROM AUTHOR]

Objective: To establish the prevalence of adrenal insufficiency (AI) in children with eosinophilic esophagitis treated with swallowed fluticasone propionate (FP) or budesonide.Study Design: Children treated with FP or budesonide for ≥ 6 months underwent a low-dose adrenocorticotropin stimulation test. Patients using systemic, inhaled, intranasal, or topical glucocorticoids were excluded. The primary outcome is AI, defined as peak serum cortisol <18 μg/dL (≤ 495 nmol/L).Results: Of 58 patients (81% male), 67% were on FP (median age 13.7 years [range 4.3-19.1], dose 1320 μg/d [440-1760], treatment duration 4.0 years [0.6-13.5]). Thirty-three percent were on budesonide (median age 10.7 years [range 3.2-17.2], dose 1000 μg/d [500-2000], treatment duration 3.4 years [0.6-7.7]). The overall prevalence of abnormal peak cortisol response (≤ 20 μg/dL) was 15% (95% CI 6%-25%) (indeterminate [18-20 μg/dL] 5% [n = 3] vs AI [<18 μg/dL] 10% [n = 6]). All patients on budesonide had a normal response vs only 77% of patients on FP (P = .02), all of whom were taking FP at a dose >440 μg/d.Conclusions: AI was present in 10% of children treated with swallowed glucocorticoids for ≥ 6 months and was found only in those treated with FP >440 μg/d. We recommend low-dose adrenocorticotropin stimulation testing in children treated long term with high dose FP to allow early detection of AI. [ABSTRACT FROM AUTHOR]

Background The Academy of Nutrition and Dietetics recommends children attending full-time child care obtain one-half to two-thirds of daily nutrient needs during their time at the child-care center, leaving one-third to one-half to be consumed away from the center. Although there are guidelines to optimize dietary intake of children attending child care, little is known about what these children consume away from the center. Objective To describe the dietary intake away from the child-care center for preschool-aged children relative to the expected one-third to one-half proportion of recommended intake, and to examine the relationships between energy intake away from the center with weight status, food group consumption, and low-income status. Design Cross-sectional study conducted between November 2009 and January 2011. Participants/setting Participants (n=339) attended 30 randomly selected, licensed, full-time child-care centers in Hamilton County, OH. Main outcome measures Child weight status and dietary intake (food/beverages consumed outside the child-care setting from the time of pickup from the center to the child’s bedtime), including energy and servings of fruits, vegetables, milk, 100% juice, sugar-sweetened beverages, and snack foods. Statistical analyses performed Generalized linear mixed models were used to examine independent associations of food group servings and low-income status to energy intake and energy intake to child weight status. Results The mean energy intake consumed away from the center (685±17 kcal) was more than the recommended target range (433 to 650 kcal). Intakes of fruits, vegetables, and milk were less than recommended. Food group servings and overweight/obesity status were positively associated with energy intake while away from the center. Conclusions Preschool-aged children consume more energy and less fruits, vegetables, and milk outside of child-care centers than recommended. Overweight status was associated with children’s dietary intake after leaving the child-care center. It may be beneficial to include parents in obesity prevention efforts targeting children attending child-care centers. [ABSTRACT FROM AUTHOR]

Background: There is a high prevalence of smoking among caregivers who bring their children to the pediatric emergency department (PED) and even higher rates of tobacco smoke exposure (TSE) and related morbidity among their children. The PED visit presents an opportunity to intervene with caregivers, but it is unknown whether they are more likely to quit if their child has a TSE-related illness. We sought to examine a PED-based smoking cessation intervention and compare outcomes based on children's TSE-related illness.Methods: A single-arm, prospective trial, with baseline, 3, and 6 month assessments was used in this study. Caregivers whose child had either a TSE-related (n=100) or non-TSE-related illness (n=100) were given a brief intervention consisting of counseling, referral to the Quitline, and free nicotine replacement therapy.Results: Participants were 91.5% female, 50.5% African American, 100% Medicaid recipients, 30.8 years old, child age mean of 5.5 years, 90% highly nicotine dependent, and 60.3% and 75.8% allowed smoking in the home and car, respectively. At follow-up (65% retention), 80% reported quit attempts at 3 months and 89% between 3 and 6 months. There were significant decreases in number of cigarettes smoked, time to first cigarette, and smoking in the home and car. Quit rates were 12.2% at 3 months, 14.6% at 6 months, and 7.3% at both time points (50% biochemically confirmed). There were no significant differences in outcomes based on children's illness.Conclusions: A brief PED-based smoking cessation intervention resulted in quit attempts and successful quits. However, the presence of a TSE-related illness did not result in different cessation outcomes. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence of pathology during routine screening of healthy short children, testing adherence to a consensus statement on the diagnosis and treatment of children with idiopathic short stature, and the cost per identified diagnosis resulting from comprehensive screening. Study design: Retrospective chart review of 1373 consecutive short stature referrals evaluated at the Cincinnati Children's Hospital Medical Center Pediatric Endocrinology Clinic between 2008 and 2011. We identified 235 patients with a height of <3rd percentile, negative history and review of systems, and normal physical examination. Outcome measures were incidence of pathology detection, diagnostic group characteristics, clinicians' adherence to testing guidelines, and screening costs. ANOVA and χ2 were used to analyze the data. Results: Nearly 99% of patients were diagnosed as possible variants of normal growth: 23% with familial short stature, 41% with constitutional delay of growth and maturation, and 36% with idiopathic short stature. The incidence of newly diagnosed pathology was 1.3%: 1 patient with biopsy-proved celiac disease, 1 with unconfirmed celiac disease, and 1 with potential insulin-like growth factor I receptor defect. On average, each patient had 64.3% of the recommended tests for age and sex; 2.1% of patients had all of the recommended testing. The total screening tests costs were $315 321, yielding $105 107 per new diagnosis entertained. Conclusions: Healthy short children do not warrant nondirected, comprehensive screening. Future guidelines for evaluating short stature should include patient-specific testing. [Copyright &y& Elsevier]

Objective To characterize the endocrine phenotype of patients with Shwachman-Diamond syndrome (SDS). Study design Clinically indicated endocrine screening data from 43 patients with SDS or SDS-like presentation were analyzed according to sex, age, and genetic testing. In addition to 25 patients with biallelic Shwachman-Bodian-Diamond syndrome (SBDS) gene mutations, we evaluated 18 patients with cytopenias who were receiving pancreatic enzyme replacement but were without SBDS mutation. We performed a retrospective review of growth records and clinically indicated endocrine evaluations. Results Of patients with SBDS mutations, 2 had low stimulated growth hormone levels, 2 had mildly elevated thyrotropin levels, 5 had abnormal glucose levels, and 1 had an elevated follicle-stimulating hormone level (post transplantation). In contrast, 1 patient without SBDS mutations had postprandial hyperglycemia and 3 had mildly low free thyroxine levels without short stature. Endocrine abnormalities were identified in 19% of short patients and 26% of the whole group. Of patients with SBDS mutations, 56% had a height expressed in SD units from the mean for age and sex of <-1.8, in contrast to only 12% of patients without SBDS mutations (38% of the whole group). Body mass index z score was significantly greater in the group with SBDS mutations (P < .001). Conclusion Although short stature was more common in patients with SBDS mutations, no consistent endocrine phenotype was observed in patients with SDS regardless of genetic testing. [ABSTRACT FROM AUTHOR]

Background: Current guidelines do not define the lower severity threshold for thrombolysis. In this study, we describe the variability of treatment of mild stroke patients across a network of academic stroke centers. Methods: Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collect data on patients treated with intravenous recombinant tissue plasminogen activator (IV rt-PA), including demographics, pretreatment National Institutes of Health Stroke Scale (NIHSS) scores, and in-hospital mortality. We examined the variability in proportion of total tissue plasminogen activator–treated patients in the NIHSS categories (0-3, 4-5, or ≥6) and associated outcomes. Results: A total of 2514 patients with reported NIHSS scores were treated with IV rt-PA between January 1, 2005 and December 31, 2009. The proportion of patients with mild stroke (NIHSS scores of 0-3) who were treated with IV rt-PA varied substantially across the centers (2.7-18.0%; P < .001). There were 5 deaths in the 256 treated with an NIHSS score of 0-3 (2.0%). The proportion of treated patients across the network with an NIHSS score of 0 to 3 increased from 4.8% in 2005 to 10.7% in 2009 (P = .001). Conclusions: There is substantial variability in the proportion of treated patients who have mild stroke across the SPOTRIAS centers, reflecting a paucity of data on how to best treat patients with mild stroke. Randomized trial data for this group of patients are needed to clarify the use of rt-PA in patients with the mildest strokes. [Copyright &y& Elsevier]

Summary: Recent studies from our laboratory have indicated that the transcription factor activator protein-2α plays a critical role in the differentiation of human villous cytotrophoblast cells to syncytiotrophoblast cells. However, little is known about the expression of activator protein-2α in placentas from pathologic pregnancies. This study compares the expression of activator protein-2α in placentas from high-risk pregnancies to gestational age–matched controls. Paracentral sections from grossly unremarkable areas of 10 placentas from each group of pregnancies complicated by mild preeclampsia, severe preeclampsia, diabetes mellitus, chronic hypertension, and fetal growth restriction and 10 control cases of placentas from normal pregnancies matched for gestational age were double immunostained for activator protein-2α and E-cadherin. The total numbers of cytotrophoblast cells and syncytiotrophoblast nuclei and the numbers of activator protein-2α–positive and activator protein-2α–negative nuclei in both of these cell types were counted by 2 pathologists blinded to disease status, in 10 representative ×40 high-power fields for each placenta. Abnormal placental maturation in most of pathologic pregnancies was evidenced by a 1.5- to 1.7-fold lower expression ratio of syncytiotrophoblast cell to cytotrophoblast cell. Activator protein-2α in syncytiotrophoblast cells was lower in mild preeclampsia, diabetes mellitus, hypertension, and fetal growth restriction (P <.0001 in each instance) and was higher by 2-fold in severe preeclampsia, although this increase was not statistically significant (P =.3). Because activator protein-2α has been shown to be critical for villous cytotrophoblast cell differentiation, our findings suggest that abnormalities in the activator protein-2α cascade of transcription factors and/or signaling molecules may contribute to the pathogenesis of the abnormal maturation in placentas in certain types of high-risk pregnancies. The different pattern of activator protein-2α expression in mild and severe preeclampsia clearly suggests that these conditions may have 2 independent pathogenic mechanisms. [Copyright &y& Elsevier]

Background: Recruitment challenges are common in acute stroke clinical trials. In a population-based study, we determined eligibility and actual enrollment for a successful, phase II acute stroke clinical trial. We hypothesized that missed opportunities for enrollment of eligible patients occurred frequently, despite the success of the trial. Methods: In 2005, acute ischemic stroke (AIS) cases in our region were identified at all 17 local hospitals as part of an epidemiologic study. The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator (CLEAR) trial assessed the safety of this combination in AIS patients within 3 hours of symptom onset. In 2005, we determined the proportion of AIS patients who were eligible for CLEAR and the proportion that were actually enrolled. Results: At 8 participating hospitals, 33 (2.8%) of 1175 AIS patients were eligible for CLEAR. Of 33 eligible patients, 18 (54.5%) were approached for enrollment, 4 (12.1%) refused, 1 (3.0%) was not consentable, and 13 (39.4%) were enrolled. Of the 15 not approached for enrollment in the trial, 10 were evaluated by the stroke team; 7 received recombinant tissue plasminogen activator. Enrollment was not associated with night or weekend presentation. Conclusions: Although the CLEAR trial was successful in meeting its delineated recruitment goals, our findings suggest enrollment could have been more efficient. Three out of 4 patients approached for enrollment participated in the trial. Eligible patients who were not approached and those treated with recombinant tissue plasminogen activator but not enrolled represent targets for improving enrollment rates. [Copyright &y& Elsevier]

Abstract: Objective: To examine the association between prenatal exposure to nicotine from tobacco smoke and infant neurobehavior using tobacco biomarkers and a sensitive and comprehensive measure of infant neurobehavior. Study design: Participants were 318 infants (206 White, 95 Black, 17 Other) and their mothers. Prenatal tobacco smoke exposure was measured twice during pregnancy and once at delivery using maternal serum cotinine. Infant neurobehavior was assessed with the NICU Network Neurobehavioral Scale at approximately 5 weeks after birth. Results: Prenatal tobacco smoke exposure was significantly associated with infant neurobehavior after controlling for important covariates, but the specific behaviors associated with exposure varied by race. In White infants, higher cotinine was associated with increased arousal (p =.030) and excitability (p =.034), and decreased self-regulation (p =.010). In contrast, among Black infants, higher cotinine was associated with decreased arousal (p =.001), excitability (p =.021), and special handling required to complete the assessment (p =.003), and increased self-regulation (p =.021) and hypotonicity (p =.016). In secondary analyses, we found racial differences in the effects of postnatal exposure to second hand smoke and low-level prenatal exposure. Conclusions: Low-level prenatal tobacco smoke exposure is associated with infant neurobehavior at 5 weeks of age, but the specific effects differ by race. These effects may reflect racial differences in nicotine metabolism that are similar to differences reported in adult and child studies of tobacco. [Copyright &y& Elsevier]

The study evaluated the effect of developmental care (DC) on short-term outcome, weight gain, and length of stay in very low-birth-weight infants (1000–1499 grams) and extremely low-birth-weight infants (<1000 grams at birth). The infants were cared for in the neonatal intensive care unit (NICU) at the University Hospital in Cincinnati. It was hypothesized that providing consistent DC to all babies in the NICU weighing 1500 grams or less at birth would increase weight gain and decrease length of stay. Data for both cohorts, predevelopmental care (preDC) and postdevelopmental care (postDC) were collected prospectively as part of the National Institutes of Health Neonatal NICU Research Network generic database on babies less than 1500 grams. This database included all variables studied and used in both cohorts. The study consisted of a pre-DC historic control and post-DC treatment group. The postDC period started 3 months after the entire staff had undergone a 4-day focused educational program on DC. This was done so that the data collected for the postDC group would occur after the initial learning curve for DC in the NICU. This study was carried out in a 50-bed level III NICU in a university teaching hospital setting. Infants weighing 1500 grams or less at birth between July of 1998 and July of 2002 were included. This population was divided into two groups: the preDC group (July 1998-July 2000) and the postDC group (2000–2002). Subgroups were then established by birth weight, less than 1000 and 1000 to 1499 grams, and the second subgroup used to separate groups less than 28 weeks gestational age and greater than 28 weeks gestational age. The total study population consisted of 292 infants. There was a statistically significant increase in weight at 36 weeks of age in the postDC period as compared to the preDC group for both the extremely low-birth-weight and very low-birth-weight groups (P < .05). The postDC group had a significant increase in the percentage of infants discharged by 40 weeks postconceptional age (P < .01). In conclusion, the successful introduction of a broad practice–based DC program in a university hospital NICU setting is described. This program coincided with significant improvement in weight gain and early discharge in preterm infants less than 1500 grams at birth. This is the first study to incorporate bubble continuous positive airway pressure into a DC regimen and the first National Institutes of Health Neonatal Network site to document positive benefits from the widespread implementation of DC practice across a single NICU. [Copyright &y& Elsevier]

Background: We sought to evaluate arterial recanalization as measured by changes in the presence of hyperdense artery sign (HAS) on initial and 24-hour computed tomography scans in patients treated with recombinant tissue plasminogen activator (rt-PA) or placebo, and to assess the effect of rt-PA on patient outcomes in this population. Methods: Patients in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial composed the study group. We determined the percentage of patients with HAS in rt-PA- and placebo-treated groups who had persistence (HAS +/+) or resolution (HAS +/–) of HAS on 24-hour computed tomography, and compared outcomes in those with resolution or persistence of the sign in these treatment groups. Results: Baseline HAS occurred in 79 of 604 eligible patients (13%). The two treatment groups were similar, although patients treated with rt-PA were significantly older. Of the 79 patients with HAS on baseline computed tomography scan, 14 of 37 (38%) treated with rt-PA had resolution of HAS at 24 hours compared with 7 of 42 (17%) treated with placebo (P = .03). Infarct volumes at 24 hours were significantly smaller in patients treated with rt-PA with resolution of the sign, compared with those who had persistence of the sign (P = .004). In our analysis, functional outcomes were not significantly improved based on resolution of HAS in either treatment group. There were 4 symptomatic ICHs in the rt-PA–treated group with HAS as compared with two in the placebo-treated group. Conclusion: Among patients with HAS at baseline in the NINDS rt-PA Stroke Trial, intravenous rt-PA increased recanalization as measured by resolution of HAS and reduced infarct volumes at 24 hours. [Copyright &y& Elsevier]

We have previously reported that family history of intracerebral hemorrhage (ICH) was associated with both lobar and nonlobar ICH. We sought to further examine this finding by analyzing differences by age and by apolipoprotein E (Apo E) genotype. All cases of hemorrhagic stroke in the greater Cincinnati area were identified through retrospective screening, and a subset was invited to undergo a direct interview and genetic testing. Interviewed subjects were matched to 2 controls by age, race, and sex. Conditional stepwise logistic regression modeling was used to determine whether having a first-degree relative with an ICH (FHICH) was an independent risk factor for ICH. Between May 1997 and December 2002, we recruited 333 cases of ICH. FHICH was found to be an independent risk factor for both lobar ICH (odds ratio [OR] = 3.9; P = .04) and nonlobar ICH (OR ratio = 5.4; P = .01) after controlling for the presence of numerous variables. Among nonlobar ICH cases, the risk appeared to be predominately in those age <70 years. The presence of Apo E4 was associated with lobar ICH at age ≥70 years but not at age <70 years. Family history of ICH appears to be a significant risk factor for nonlobar ICH at age <70 years. The presence of Apo E4 appears to be a risk factor for lobar ICH at age ≥70 years but not at age <70 years. Family history of ICH is a risk factor for lobar ICH after controlling for the presence of Apo E4. [Copyright &y& Elsevier]

Background: Vitamin K has been suggested to have a role in bone metabolism, and low vitamin K intake has been related to low bone density and increased risk of osteoporotic fracture. Objective: The objective of this study was to determine whether phylloquinone (vitamin K1) intake and biochemical indicators of vitamin K status are related to bone mineral content (BMC) and markers of bone formation and bone resorption in girls. Design: Vitamin K status [plasma phylloquinone concentration and percentage of undercarboxylated osteocalcin (%ucOC)] was measured at baseline in a study of 245 healthy girls aged 3-16 y. Crosslinked N-telopeptide of type 1 collagen (NTx) breakdown, osteocalcin, and bone-specific alkaline phosphatase were measured to reflect bone resorption and formation. BMC of the total body, lumbar spine, and hip and dietary phylloquinone intake were measured annually for 4 y. Results: Phylloquinone intake (median: 45 μg/d) was not consistently associated with bone turnover markers or BMC. Better vitamin K status (high plasma phylloquinone and low %ucOC) was associated with lower bone resorption and formation. Plasma phylloquinone was inversely associated with NTx and osteocalcin concentrations (P < 0.05), and %ucOC was positively associated with NTx and bone-specific alkaline phosphatase concentrations (P < 0.05). Indicators of vitamin K status were not consistently associated with current BMC or gain in BMC over the 4-y study period. Conclusions: Better vitamin K status was associated with decreased bone turnover in healthy girls consuming a typical US diet. Randomized phylloquinone supplementation trials are needed to further understand the potential benefits of phylloquinone on bone acquisition in growing children. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate placental lesions found in women with preeclampsia compared with normotensive control subjects and to determine whether the presence of these lesions are related to gestational age at delivery.Study Design: Placental disease of women with preeclampsia at 24 to 42 weeks of gestation was compared with the placental disease of normotensive gestational age-matched control subjects. The placental lesions that were studied specifically included decidual arteriolopathy, thrombi in the fetal circulation, central infarction, intervillous thrombi, and hypermaturity of villi. Data analysis involved the chi(2) test, the Student t test, and logistic regression; odds ratios and CIs were estimated.Results: Placentas from women with preeclampsia (n=158) and normotensive control subjects (n=156) were evaluated. Among women with preeclampsia, 67% had severe disease. Placental lesions were studied according to gestational age at delivery: <28, 28 to 32, 33 to 36, and >or=37 weeks of gestation. Of the placental lesions that were studied, decidual arteriolopathy (odds ratio, 23.8, 95% CI 10.0-57.0), hypermaturity of villi (odds ratio, 12.4; 95% CI 5.3-29.2), intervillous thrombi (odds ratio, 1.95;95% CI 1.0-3.7), central infarction (odds ratio, 5.9; 95% CI 3.1-11.1), and thrombi in the fetal circulation (odds ratio, 2.8; 95% CI 1.2-6.6) were found to have significantly higher rates in the preeclamptic group. In contrast, the rate of chorioamnionitis was significantly lower in the preeclamptic group (odds ratio, 0.2; 95% CI 0.1-0.4). The rates of abruptio placentae and meconium staining were not different between the two groups. Within the preeclamptic group, the rates of decidual arteriolopathy (P<.0001), central infarction (P=.0001), and hypermaturity of villi (P<.0001) were higher the earlier the gestational age at delivery.Conclusion: Placentas in women with preeclampsia have increased amounts of disease. The rate is increased with lower gestational ages at the time of delivery for women with preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Calcium supplements increase bone mass in children, but the effect does not persist once supplementation is discontinued. Objective: The objective of this study was to determine whether milk intake during childhood and adolescence, when controlled for current calcium intake, is associated with adult bone mass (ie, bone mineral content), bone mineral density, and the incidence of osteoporotic fracture. Design: We used data from the third National Health and Nutrition Examination Survey of 3251 non-Hispanic, white women age ? 20 y. Bone density was measured at the hip. History of fracture of the hip, spine, or forearm was classified as a lifetime fracture (occurring after age 13 y) or an osteoporotic fracture (occurring after age 50 y). Subjects reported frequency of milk consumption during childhood (aged 5-12 y) and during adolescence (aged 13-17 y). Regression models controlled for weight, height, age, menopause and use of estrogen, physical activity, smoking, and current calcium intake. Results: Among women aged 20-49 y, bone mineral content was 5.6% lower in those who consumed < 1 serving of milk/wk (low intake) than in those who consumed > 1 serving/d (high intake) during childhood (P < 0.01). Low milk intake during adolescence was associated with a 3% reduction in hip bone mineral content and bone mineral density (P < 0.02). Among women aged ⩾ 50 y, there was a nonlinear association between milk intake during childhood and adolescence and hip bone mineral content and bone mineral density (P < 0.04). Low milk intake during childhood was associated with a 2-fold greater risk of fracture (P < 0.05). Conclusion: Women with low milk intake during childhood and adolescence have less bone mass in adulthood and greater risk of fracture. [ABSTRACT FROM AUTHOR]

Objective: To determine whether an elevated serum P:E2 ratio on the day of hCG administration during gonadotropin stimulation for intrauterine insemination (IUI) or IVF is associated with diminished ovarian reserve.Design: Retrospective chart review.Setting: Tertiary fertility center.Patient(s): Two hundred eighty-six women undergoing a fertility evaluation.Intervention(s): Clomiphene citrate challenge test (CCCT).Main Outcome Measure(s): E2 and P concentrations on the day of hCG administration.Result(s): For the IUI group (n = 98), 74 women had a normal CCCT, while 24 had an abnormal CCCT. For women undergoing IVF (n = 188), 171 had a normal CCCT and 17 had an abnormal CCCT. For women undergoing IUI with a normal CCCT, 33 (44%) had a [(P/E2) × 1000] ratio <1 on the day of hCG, while 12 (50%) (abnormal CCCT) had a [(P/E2) × 1000] ratio <1. Similarly, for women doing IVF with a normal CCCT, 96 (56%) had a [(P/E2) × 1000] ratio <1 on the day of hCG, and 9 (44%) (abnormal CCCT) had a [(P/E2) × 1000] ratio <1 on the day of hCG. The frequencies were similar for all comparable groups. For both groups, there was no association between serum (P/E2) × 1000 on the day of hCG administration and day 3 or 10 FSH during the CCCT. For women with a normal CCCT, there were no differences in delivery rates based on the (P/E2) × 1000 ratio.Conclusion(s): In women stimulated with hMG for IUI or IVF, the serum P:E2 ratio on the day of hCG administration is not associated with diminished ovarian reserve, as demonstrated by the CCCT, or pregnancy outcome. [Copyright &y& Elsevier]

Determines the effects of chronic reduction in uterine blood flow on umbilical blood flow and fetal cardiovascular dynamics in late-terms sheep. Gestational age; Maternal and fetal blood pressure and heart rate; Fetal growth; Correlation between umbilical blood flow and uterine blood flow.

Infertile women undergoing ovulation induction (OI) with clomiphene citrate (CC) who have adequate follicular recruitment and an endometrial thickness of <7 mm as determined by transvaginal sonography in the late follicular phase were switched to tamoxifen for OI in a subsequent cycle. A comparison between the endometrial thickness on CC and tamoxifen was made with by paired analysis. For women undergoing OI with CC who have adequate follicular recruitment and thin endometrium (<7 mm), switching to tamoxifen in subsequent cycles improves endometrial thickness. [Copyright &y& Elsevier]