Trends Over Time in Stroke Incidence by Race in the Greater Cincinnati Northern Kentucky Stroke Study.

BACKGROUND AND OBJECTIVES: Understanding the current status of and temporal trends of stroke epidemiology by age, race, and stroke subtype is critical to evaluate past prevention efforts and to plan future interventions to eliminate existing inequities. We investigated trends in stroke incidence and case fatality over a 22-year time period. METHODS: In this population-based stroke surveillance study, all cases of stroke in acute care hospitals within a 5-county population of southern Ohio/northern Kentucky in adults aged ≥20 years were ascertained during a full year every 5 years from 1993 to 2015. Temporal trends in stroke epidemiology were evaluated by age, race (Black or White), and subtype (ischemic stroke [IS], intracranial hemorrhage [ICH], or subarachnoid hemorrhage [SAH]). Stroke incidence rates per 100,000 individuals from 1993 to 2015 were calculated using US Census data and age-standardized, race-standardized, and sex-standardized as appropriate. Thirty-day case fatality rates were also reported. RESULTS: Incidence rates for stroke of any type and IS decreased in the combined population and among White individuals (any type, per 100,000, 215 [95% CI 204-226] in 1993/4 to 170 [95% CI 161-179] in 2015, p = 0.015). Among Black individuals, incidence rates for stroke of any type decreased over the study period (per 100,000, 349 [95% CI 311-386] in 1993/4 to 311 [95% CI 282-340] in 2015, p = 0.015). Incidence of ICH was stable over time in the combined population and in race-specific subgroups, and SAH decreased in the combined groups and in White adults. Incidence rates among Black adults were higher than those of White adults in all time periods, and Black:White risk ratios were highest in adults in young and middle age groups. Case fatality rates were similar by race and by time period with the exception of SAH in which 30-day case fatality rates decreased in the combined population and White adults over time. DISCUSSION: Stroke incidence is decreasing over time in both Black and White adults, an encouraging trend in the burden of cerebrovascular disease in the US population. Unfortunately, however, Black:White disparities have not decreased over a 22-year period, especially among younger and middle-aged adults, suggesting the need for more effective interventions to eliminate inequities by race.

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.

Environmental predictors of children's executive functioning development.

Executive functioning (EF) abilities develop through childhood, but this development can be impacted by various psychosocial environmental influences. Using longitudinal data from the Health Outcome and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort study, we examined if psychosocial environmental factors were significant predictors of EF development. Study participants comprised 271 children and their primary caregivers (98.5% mothers) followed from birth to age 12. We identified four distinct EF developmental trajectory groups comprising a consistently impaired group (13.3%), a descending impairment group (27.7%), an ascending impairment group (9.95%), and a consistently not impaired group (49.1%). Higher levels of maternal ADHD and relational frustration appear to be risk factors for increased EF difficulty over time, while higher family income may serve as a protective factor delaying predisposed EF impairment. Important intervention targets might include teaching positive and effective parenting strategies to mothers whose children are at risk for EF dysfunction.

Descriptive Epidemiology of Game-Related Youth Flag Football Injuries.

CONTEXT: Flag football is promoted as a safer alternative to tackle football. This may be 1 reason why participation rates have risen by 39% over the past 3 years. Despite rising participation, epidemiologic research on sport-specific injuries and associated relative risk is lacking. OBJECTIVE: To prospectively document the epidemiology of injuries in youth flag football. DESIGN: Descriptive epidemiology study. SETTING: Regional and national youth flag football tournaments. PATIENTS OR OTHER PARTICIPANTS: Athletes (N = 1939; 1744 boys and 195 girls), ages 6 to 12 years. An athletic trainer prospectively monitored the athletes for sport-related injury and exposures. MAIN OUTCOME MEASURE(S): Athlete risks of injury and injury rates were calculated overall and by sex. Injury characteristics were reported for the total population and by sex. RESULTS: Forty-seven injuries to unique individuals were recorded in 1939 athletes with a total of 9228 athlete-exposures (AEs). The overall risk of injury was 2.4% (95% CI = 1.79%, 3.21%), with an overall injury rate of 5.1 per 1000 AEs (95% CI = 3.75, 6.77). Of the 47 injuries, 36 occurred in boys (8365 AEs), and 11 occurred in girls (863 AEs). A higher risk in girls was evidenced by both the injury risk ratio (2.73; 95% CI = 1.41, 5.30) and injury rate ratio of 2.96 (95% CI = 1.51, 5.82). The most common injury sites were the head/face/neck (n = 15, 31.9%), followed by the ankle/foot (n = 9, 19.1%). The most frequent types of injury were contusion (55.3%), sprain/subluxation (14.9%), and general trauma (10.6%); 74.5% of all injuries resulted from direct impact. CONCLUSIONS: Although the competition injury rate for youth flag football was lower than the values from studies reporting comparable tackle football data, the frequencies by body part, type, and mechanism were similar. Given that most injuries were related to some form of impact and predominantly contusions, adopting minimal protective equipment or padding may reduce the numbers of these injuries.

Changing Trends in Demographics, Risk Factors, and Clinical Features of Patients With Infective Endocarditis-Related Stroke, 2005-2015.

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

Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial.

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

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.

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.

A Joint Model for Unbalanced Nested Repeated Measures with Informative Drop-Out Applied to Ambulatory Blood Pressure Monitoring Data.

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

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.

Elevated Anthropometric and Metabolic Indicators among Young Adult Offspring of Mothers with Pregestational Diabetes: Early Results from the Transgenerational Effect on Adult Morbidity Study (the TEAM Study).

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

Comparing adolescent self staging of pubertal development with hormone biomarkers.

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

Loss of Control Eating and Health Indicators Over 6 Years in Adolescents Undergoing Metabolic and Bariatric Surgery.

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

Examination of the '5-2-1-0' Recommendations in Racially Diverse Young Children Exposed to Tobacco Smoke.

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

Gestational Exposure to Phthalates and Social Responsiveness Scores in Children Using Quantile Regression: The EARLI and HOME Studies.

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.

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.

A Parental Smoking Cessation Intervention in the Pediatric Emergency Setting: A Randomized Trial.

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 ≤$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 (-2 [-5, 0] versus 0 [-4, 0], p = 0.0008),at T2 from baseline (-4 [-9, -1] vs. -2 [-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's health. Cessation interventions in this setting may result in adult and pediatric public health benefits.

Provision of free nicotine replacement therapy to parental smokers in the pediatric emergency setting.

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

Oral bisphosphonate treatment in patients with Duchenne muscular dystrophy on long term glucocorticoid therapy.

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