Projections of Endovascular Therapy-Eligible Patients With Stroke for the US Population.

BACKGROUND: As stroke endovascular thrombectomy (EVT) treatment indications expand, understanding population-based EVT eligibility becomes critical for resource planning. We aimed to project current and future population-based EVT eligibility in the United States. METHODS: We conducted a post hoc analysis of the physician-adjudicated GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study; 2015 epoch), a population-based, cross sectional, observational study of stroke incidence, treatment, and outcomes across a 5-county region. All hospitalized patients ≥18 years of age with acute ischemic stroke were ascertained using the International Classification of Diseases, Ninth Revision codes 430-436 and Tenth Revision codes I60-I67 and G45-G46 and extrapolated to the US adult census 2020. We determined the rate of EVT eligibility within the GCNKSS population using time from last known well to presentation (0-5 versus 5-23 hours), presenting National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale. Both conservative and liberal estimates of prevalence of large vessel occlusion and large core were then applied based on literature review (unavailable within the 2015 GCNKSS). This eligibility was then extrapolated to the 2020 US population. RESULTS: Of the 1 057 183 adults within GCNKSS in 2015, 2741 had an ischemic stroke and 2176 had data available for analysis. We calculated that 8659 to 17 219 patients (conservative to liberal) meet the current guideline-recommended EVT criteria (nonlarge core, no prestroke disability, and National Institutes of Health Stroke Scale score ≥6) in the United States. Estimates (conservative to liberal) for expanded EVT eligibility subpopulations include (1) 5316 to 10 635 by large core; (2) 10 635 to 21 270 by mild presenting deficits with low National Institutes of Health Stroke Scale score; (3) 13 572 to 27 089 by higher prestroke disability; and (4) 7039 to 14 180 by >1 criteria. These expanded eligibility subpopulations amount to 36 562 to 73 174 patients. CONCLUSIONS: An estimated 8659 to 17 219 adult patients in the United States met strict EVT eligibility criteria in 2020. A 4-fold increase in population-based EVT eligibility can be anticipated with incremental adoption of recent or future positive trials. US stroke systems need to be rapidly optimized to handle all EVT-eligible patients with stroke.

Gestational PBDE concentrations, persistent externalizing, and emerging internalizing behaviors in adolescents: The HOME study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals used as flame retardants in commercial and consumer products. Gestational PBDE concentrations are associated with adverse behaviors in children; however, the persistence of these associations into adolescence remains understudied. OBJECTIVE: We estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported behaviors at age 12 years and determined the consistency with previously observed associations in childhood with caregiver-reported behaviors in a prospective pregnancy and birth cohort. METHODS: We measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑5BDE: 28, -47, -99, -100 and -153) during pregnancy. At age 12 years, we assessed behaviors for 237 adolescents using self- and caregiver-reports with the Behavioral Assessment System for Children-3 (BASC3). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log10-transformed gestational PBDE concentrations with BASC3 scores. We obtained estimates and 95% confidence intervals through a bootstrapping approach. We evaluated potential effect measure modification (EMM) of adolescent sex by examining sex-stratified regression models and estimating the EMM p-values. RESULTS: Gestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, -99, -100, ∑5BDE), internalizing problems (BDE-28, -47, -99), functional impairment (BDE-28, ∑5BDE), and emotional symptoms (BDE-28). Gestational PBDE concentrations were positively associated with caregiver-reported BASC3 composite indices for externalizing problems (BDE-28, -47, -99, -100, -153, ∑5BDE) and behavioral symptoms (BDE-99). For caregiver reported behaviors, we observed stronger associations with gestational BDE concentrations among males, especially for executive functioning (BDE-28, -47, -99, -100, ∑5BDE). DISCUSSION: Gestational PBDE serum concentrations were associated with self-reported internalizing and externalizing behavior problems in early adolescence. Caregiver-reported externalizing behaviors recognized during childhood remain associated with gestational PBDE concentrations and persist into early adolescence. Internalizing behaviors were less recognized by caregivers.

Unraveling the magnesium connection: the Cincinnati PPG's pioneering work on mineral metabolism in diabetes in pregnancy.

OBJECTIVE: to review the contribution of the Cincinnati Program Project grant (PPG) to the understanding and treatment of neonatal hypocalcemia (NHC) in infants of mothers with diabetes. STUDY DESIGN: retrospective review of the PPG publications related to mineral metabolism in type 1 diabetic pregnant women Results: the PPG investigators first described the epidemiology and the additional risk factors for NHC, namely prematurity and neonatal asphyxia, but they also recognized the independent effect of maternal diabetes mellitus. They explored the link between NHC and maternal/neonatal hypomagnesemia, and finally conducted a - randomized controlled trial that demonstrated the ability to prevent NHC by administration of magnesium sulfate soon after birth. CONCLUSION: The PPG in its various phases revealed the important role that Magnesium plays in the regulation of mineral metabolism in pregnancy and, in particular, in pregnancies complicated by pre-gestational diabetes. .

EMBRYONIC, FETAL, AND NEONATAL COMPLICATIONS IN INFANTS OF DIABETIC MOTHERS: INSIGHTS FROM THE CINCINNATI DIABETES IN PREGNANCY PROGRAM PROJECT GRANT.

OBJECTIVE: To review how the Cincinnati Diabetes in Pregnancy Program Project Grant (PPG) contributed to understanding and treatment of neonatal complications in infants of diabetic mothers (IDMs) Study Design: Retrospective review of all PPG work on glycemic control at different pregnancy timepoints and its association with embryonic, fetal and neonatal complications, such as congenital malformations (CMs), intrauterine growth restriction (IUGR), macrosomia, hypoglycemia, respiratory distress syndrome (RDS), asphyxia and polycythemia. RESULTS: we found that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal hypoglycemic episodes or insulin therapy, are independent risk factors for major CMs. A suggestive association of major CMs with maternal Magnesium deficiency was also observed. Poor glycemic control during late embryogenesis and early fetal development was associated with an increased risk of minor CMs. We described a biphasic pattern of fetal growth; whereby early growth delay was followed by enhanced fetal growth which was associated with neonatal macrosomia. Macrosomia was associated with poorer glycemic control in the third trimester and an increased risk of birth trauma. Macrosomia was also correlated with animal-origin insulin concentrations in cord blood, demonstrating that insulin bound to antibodies can cross the placenta and may affect the fetus. We also showed that neonatal hypoglycemia was significantly associated with third trimester glycemic control, in addition to hyperglycemia occurring during labor. With modern management and adequate prenatal care, IDMs are no longer at increased risk for RDS. Perinatal asphyxia was associated with increased proteinuria appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. Polycythemia in IDMs is prevalent and correlates with proxy measurements of fetal hypoxemia (nucleated red blood cells at delivery) and poorer glycemic control in late pregnancy. CONCLUSION: The PPG in its various phases revealed the important role of glycemic control at nearly every stage of pregnancy including labor.

Temporal Trends in Public Stroke Knowledge, 1995-2021.

BACKGROUND: Outreach campaigns have sought to reduce the burden of stroke by improving knowledge of stroke risk factors (RF) and warning signs (WS). We describe trends in stroke knowledge from 1995 to 2021. METHODS: From 1995 to 2021, 6 separate surveys were conducted in the Greater Cincinnati Northern Kentucky Region. Temporal trends in RF/WS knowledge were analyzed using logistic regression adjusting for Race, sex, age, and education. RESULTS: In 1995, 28.6% of participants (537/1880) could name ≥2 WS, compared with 50.6% (983/1944) in 2021 (trend P<0.0001 after adjustment). In 1995, 44.5% of participants (836/1880) knew ≥2 RF, compared with 56.7% (1103/1944) in 2021 (trend P<0.0001 after adjustment). Although still improved compared with 1995, fewer participants could identify ≥2 RF in 2021 (1103/1944, 56.7%) when compared with 2011 (1287/2036, 63.2%, pairwise P<0.05). This decline in RF knowledge was disproportionately larger in women (odds ratio of 0.67 for knowledge in 2021 compared with 2011 in females, P=0.047 for the interaction between sex and study year). CONCLUSIONS: Although stroke knowledge has overall improved since 1995, there is evidence for lost gains since 2011, particularly in women. Stroke outreach campaigns need ongoing evaluation.

Screening for Gastric Sensory Motor Abnormalities in Pediatric Patients With Type 1 Diabetes.

OBJECTIVE: To determine the frequency of gastric sensory motor symptoms in youth with type 1 diabetes. METHODS: A prospective cross-sectional study was performed to evaluate symptoms of delayed gastric emptying in participants with type 1 diabetes, aged 12 to 25 years, using the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire. In addition, a 5-year (January 2015 to December 2019), a retrospective study was completed on all gastric emptying scans performed in youth at our institution. RESULTS: A total of 359 participants (mean age, 17.7 ± 3.33 years) with type 1 diabetes completed the GCSI questionnaire. Compared with nonresponders, responders were more likely to be non-Hispanic White (90% vs 86%; P =.003) and female patients (58% vs 44%; P <.0001), with a lower HbA1c (8.1 ± 1.8 vs 9.0 ± 2.1; P <.0001). At least 1 gastrointestinal symptom was reported in 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 =.01). In the retrospective study, 778 underwent gastric emptying scan, 29 participants had type 1 diabetes and 11 (38%) showed delayed gastric emptying. CONCLUSION: Gastrointestinal symptoms related to gastric sensory motor abnormalities are seen in youth and young adults with type 1 diabetes. In particular, for those with higher GCSI scores, earlier recognition and referral may be warranted.

Substance Use and Performance of Toxicology Screens in the Greater Cincinnati Northern Kentucky Stroke Study.

BACKGROUND: Though stroke risk factors such as substance use may vary with age, less is known about trends in substance use over time or about performance of toxicology screens in young adults with stroke. METHODS: Using the Greater Cincinnati Northern Kentucky Stroke Study, a population-based study in a 5-county region comprising 1.3 million people, we reported the frequency of documented substance use (cocaine/marijuana/opiates/other) obtained from electronic medical record review, overall and by race/gender subgroups among physician-adjudicated stroke events (ischemic and hemorrhagic) in adults 20 to 54 years of age. Secondary analyses included heavy alcohol use and cigarette smoking. Data were reported for 5 one-year periods spanning 22 years (1993/1994-2015), and trends over time were tested. For 2015, to evaluate factors associated with performance of toxicology screens, multiple logistic regression was performed. RESULTS: Overall, 2152 strokes were included: 74.5% were ischemic, mean age was 45.7±7.6, 50.0% were women, and 35.9% were Black. Substance use was documented in 4.4%, 10.4%, 19.2%, 24.0%, and 28.8% of cases in 1993/1994, 1999, 2005, 2010, and 2015, respectively (Ptrend<0.001). Between 1993/1994 and 2015, documented substance use increased in all demographic subgroups. Adjusting for gender, comorbidities, and National Institutes of Health Stroke Scale, predictors of toxicology screens included Black race (adjusted odds ratio, 1.58 [95% CI, 1.02-2.45]), younger age (adjusted odds ratio, 0.70 [95% CI, 0.53-0.91], per 10 years), current smoking (adjusted odds ratio, 1.62 [95% CI, 1.06-2.46]), and treatment at an academic hospital (adjusted odds ratio, 1.80 [95% CI, 1.14-2.84]). After adding chart-reported substance use to the model, only chart-reported substance abuse and age were significant. CONCLUSIONS: In a population-based study of young adults with stroke, documented substance use increased over time, and documentation of substance use was higher among Black compared with White individuals. Further work is needed to confirm race-based disparities and trends in substance use given the potential for bias in screening and documentation. Findings suggest a need for more standardized toxicology screening.

Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns.

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%; I2, 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<0.0001). Cohort site and National Institutes of Health Stroke Severity scale >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.

Protein QTL analysis of IGF-I and its binding proteins provides insights into growth biology.

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

Early exposure to flame retardants is prospectively associated with anxiety symptoms in adolescents: A prospective birth cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: After adjusting for predetermined covariates, each doubling in maternal PBDE concentrations was associated with increased SCARED scores (e.g., for ∑PBDE, SCARED total score, ß = 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, ß = .8, 95% CI: -0.2-1.8, p = .11). CONCLUSIONS: 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.

Frequency and Severity of Hypothyroidism During TKI Therapy in the Pediatric and Young Adult Population.

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.

Association of diet quality, physical activity, and abdominal obesity with metabolic syndrome z-score in black and white adolescents in the US.

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 [ß (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.

Opportunities for Enhanced Transition of Care Preparation for Adolescents and Emerging Adults With Type 1 Diabetes: Use of the READDY Transition Tool.

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

The effect of oral bisphosphonate therapy on vertebral morphometry and fractures in patients with Duchenne muscular dystrophy and glucocorticoid-induced osteoporosis.

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

Flexible multivariate joint model of longitudinal intensity and binary process for medical monitoring of frequently collected data.

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

Temporal Trends in Stroke Incidence Over Time by Sex and Age in the GCNKSS.

Background and Purpose- Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods- Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results- Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215-242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163-185) in 2015 (P<0.05), compared with 282 (95% CI, 263-301) in 1993/1994 to 211 (95% CI, 198-225) in 2015 (P<0.05) in men. Incidence rates decreased between the first and last study periods in both sexes for IS but not for intracerebral hemorrhage or subarachnoid hemorrhage. Significant decreases in stroke incidence occurred between the first and last study periods for both sexes in the 65- to 84-year age group and men only in the ≥85-year age group; stroke incidence increased for men only in the 20- to 44-year age group. Conclusions- Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.

Nutritional Risks in Adolescents After Bariatric Surgery.

BACKGROUND & AIMS: Little is known about prevalence and risk factors for nutritional deficiencies in adolescents after metabolic bariatric surgery. We performed a 5-year prospective cohort study of these. METHODS: Adolescents who had Roux-en-Y gastric bypass (RYGB, n = 161) or vertical sleeve gastrectomy (VSG, n = 67) were enrolled at 5 tertiary-care centers from March 2007 through February 2012. The final analysis cohort included 226 participants (161 who had RYGB and 65 who had VSG). We measured serum levels of ferritin; red blood cell folate; vitamins A, D, B1, B12; and parathyroid hormone at baseline and annually for 5 years. General linear mixed models were used to examine changes over time and identify factors associated with nutritional deficiencies. RESULTS: The participants were 75% female and 72% white, with a mean age of 16.5 ± 1.6 years and mean body mass index of 52.7 ± 9.4 kg/m2 at surgery. Mean body mass index decreased 23% at 5 years, and did not differ significantly between procedures. After RYGB, but not VSG, serum concentrations of vitamin B12 significantly decreased whereas serum levels of transferrin and parathyroid hormone increased. Ferritin levels decreased significantly after both procedures. Hypo-ferritinemia was observed in 2.5% of patients before RYGB and 71% at 5 y after RYGB (P < .0001), and 11% of patients before VSG and 45% 5 y after VSG (P = .002). No significant changes in serum levels of folate or vitamins A, B1, or D were found between baseline and 5 y after either procedure. By 5 y, 59% of RYGB and 27% of VSG recipients had 2 or more nutritional deficiencies. Risk factors associated with specific deficiencies included surgery type, female sex, black race, supplementation intake, weight regain, and for females, pregnancy. CONCLUSIONS: In a prospective study of adolescents who underwent RYGB or VSG, we observed nutritional deficiencies by 5 y after the procedures-particularly in iron and B12 after RYGB. Ongoing nutrient monitoring and supplementation are recommended for all patients, but surgery type, supplementation intake, sex, and race might affect risk. (Clinical trial registration: Adolescent Bariatrics: Assessing Health Benefits and Risk [also known as Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS)], NCT00474318.).

Utilization of a Clinical Decision Support Tool to Reduce Child Tobacco Smoke Exposure in the Urgent Care Setting.

BACKGROUND: Clinical decision support systems (CDSS) may facilitate caregiver tobacco screening and counseling by pediatric urgent care (UC) nurses. OBJECTIVE: This study aimed to assess the feasibility of a CDSS to address caregivers' tobacco use and child tobacco smoke exposure (TSE). METHODS: We conducted a 3-month prospective study on caregivers screened using a CDSS. Nurses used the CDSS to advise, assess, and assist caregivers to quit. We assessed caregiver sociodemographics, smoking habits, and child TSE. RESULTS: We screened 185 caregivers whose children were exposed to TSE for study inclusion; 155 (84%) met the eligibility criteria, and 149 (80.5%) were included in the study. Study nurses advised 35.2% of the caregivers to quit, assessed 35.9% for readiness to quit, and assisted 32.4%. Of the 149 participants, 83.1% were female; 47.0% were white and 45.6% African American; 84.6% had public insurance or were self-pay; 71.1% were highly nicotine dependent; 50.0% and 50.7% allowed smoking in the home and car, respectively; and 81.3% of children were biochemically confirmed to be exposed to tobacco smoke. At follow-up (86.6% retention), 58.9% reported quit attempts at 3 months. There was a significant decrease in nicotine dependence and a significant increase in motivation to quit. Self-reported quit rate was 7.8% at 3 months. CONCLUSIONS: An electronic health record-embedded CDSS was feasible to incorporate into busy UC nurses' workloads and was associated with encouraging changes in the smoking behavior of caregivers. More research on the use of CDSS to screen and counsel caregivers who smoke in the UC and other acute care settings is warranted.

lifetime exposure to traffic-related air pollution and symptoms of depression and anxiety at age 12 years.

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

Nonmedically Indicated Induction of Labor Compared with Expectant Management in Nulliparous Women Aged 35 Years or Older.

OBJECTIVE: This article compares maternal and neonatal outcomes in women aged ≥ 35 years who experienced nonmedically indicated induction of labor (NMII) versus expectant management. STUDY DESIGN: This was a retrospective cohort study of nulliparas aged ≥ 35 years with a singleton and cephalic presentation who delivered at term. Outcomes were compared between women who underwent NMII at 37, 38, 39, and 40 weeks' gestation and those with expectant management that week. Adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs) were calculated, controlling for predefined covariates. RESULTS: Of 3,819 nulliparas aged ≥ 35 years, 1,409 (36.9%) women underwent NMII. Overall at 39 weeks' gestation or later, maternal and neonatal outcomes were similar or improved with NMII. At 37, 38, and 39 weeks' gestation, NMII compared with expectant management was associated with decreased odds of cesarean delivery at 37, 38, and 39 weeks' gestation. At 40 weeks' gestation, NMII compared with expectant management was associated with an increased odds of operative vaginal delivery and a decreased odds of neonatal intensive care unit (NICU) admission. CONCLUSION: In nulliparous women aged ≥ 35 years, NMII was associated with decreased odds of cesarean delivery at 37 to 39 weeks' gestation and decreased odds of NICU admission at 40 weeks' gestation compared with expectant management.