Boot Camp Translation using Community-Engaged messaging for adolescent Vaccination: A Cluster-Randomized trial.

BACKGROUND: Routine vaccination coverage for adolescents living in the rural US is lower than adolescents living in urban areas. We sought to measure the effect of Boot Camp Translation (BCT), a community-based participatory intervention, on rural adolescent vaccination coverage. METHODS: A cluster randomized controlled trial was performed September 2018-November 2021 involving 16 rural Colorado counties. Intervention county community members engaged in BCT to develop interventions to improve adolescent vaccination locally. Adolescent vaccination coverage was measured using the Colorado Immunization Information System. RESULTS: For 11-12-year-olds, HPV initiation, HPV up-to-date, MenACWY, and Tdap vaccination coverage was lower post- versus pre-intervention in the control and intervention groups. For 11-12-year-olds in the intervention group, there was no significant difference post- versus pre-intervention in the odds of HPV vaccine initiation (adjusted ratio of odds ratios [aROR] = 0.93, 95 %: 0.85-1.02, p = 0.10) or up-to-date HPV vaccination (aROR: 1.10, 95 % CI: 0.98-1.23, p = 0.11) compared with the control group. Among 11-12-year-olds, the decrease in the proportion vaccinated with MenACWY and Tdap in the intervention group was significantly greater than the control group. Among 13-17-year-olds, there were significant increases in HPV initiation, HPV up-to-date, MenACWY, and Tdap vaccination coverage from pre- to post-intervention for both groups, with no significant differences between groups. CONCLUSION: 11-12-year-old vaccination coverage decreased slightly from pre- to post-intervention while 13-17-year-old vaccination coverage increased. We saw no effect from the BCT intervention. Our findings about the effectiveness of BCT for improving vaccine uptake may not be generalizable because the study coincided with the COVID-19 pandemic. CLINICAL TRIAL REGISTRY: This study was registered with ClinicalTrials.gov, NCT03955757.

Development and validation of a computable phenotype for Turner syndrome utilizing electronic health records from a national pediatric network.

Turner syndrome (TS) is a genetic condition occurring in ~1 in 2000 females characterized by the complete or partial absence of the second sex chromosome. TS research faces similar challenges to many other pediatric rare disease conditions, with homogenous, single-center, underpowered studies. Secondary data analyses utilizing electronic health record (EHR) have the potential to address these limitations; however, an algorithm to accurately identify TS cases in EHR data is needed. We developed a computable phenotype to identify patients with TS using PEDSnet, a pediatric research network. This computable phenotype was validated through chart review; true positives and negatives and false positives and negatives were used to assess accuracy at both primary and external validation sites. The optimal algorithm consisted of the following criteria: female sex, ≥1 outpatient encounter, and ≥3 encounters with a diagnosis code that maps to TS, yielding an average sensitivity of 0.97, specificity of 0.88, and C-statistic of 0.93 across all sites. The accuracy of any estradiol prescriptions yielded an average C-statistic of 0.91 across sites and 0.80 for transdermal and oral formulations separately. PEDSnet and computable phenotyping are powerful tools in providing large, diverse samples to pragmatically study rare pediatric conditions like TS.

Development and Validation of a Computable Phenotype for Turner Syndrome Utilizing Electronic Health Records from a National Pediatric Network.

Turner syndrome (TS) is a genetic condition occurring in ~1 in 2,000 females characterized by the complete or partial absence of the second sex chromosome. TS research faces similar challenges to many other pediatric rare disease conditions, with homogenous, single-center, underpowered studies. Secondary data analyses utilizing Electronic Health Record (EHR) have the potential to address these limitations, however, an algorithm to accurately identify TS cases in EHR data is needed. We developed a computable phenotype to identify patients with TS using PEDSnet, a pediatric research network. This computable phenotype was validated through chart review; true positives and negatives and false positives and negatives were used to assess accuracy at both primary and external validation sites. The optimal algorithm consisted of the following criteria: female sex, ≥1 outpatient encounter, and ≥3 encounters with a diagnosis code that maps to TS, yielding average sensitivity 0.97, specificity 0.88, and C-statistic 0.93 across all sites. The accuracy of any estradiol prescriptions yielded an average C-statistic of 0.91 across sites and 0.80 for transdermal and oral formulations separately. PEDSnet and computable phenotyping are powerful tools in providing large, diverse samples to pragmatically study rare pediatric conditions like TS.

Embedding Dental Hygienists into Medical Care Teams: Implementation and evaluation of a medical-dental integration approach in Colorado.

This case report describes the implementation approach and evaluation of a medical-dental integration (MDI) project in Colorado that embedded dental hygienists (DHs) into 10 medical practice settings. Through the MDI Learning Collaborative, DHs were integrated into primary care medical care practices to provide full-scope dental hygiene care to patients. Dental hygienists were trained to collect quality-improvement metrics on all encounters, including untreated tooth decay, and referred patients with restorative needs to partnering dentists. Cross-sectional, aggregated clinic-level oral health metrics were submitted monthly from 2019-2022. Descriptive statistics were used to describe the population receiving MDI care and interviews were conducted with MDI staff to describe their perspectives on this approach to comprehensive care. A logistic regression model, adjusted for time and practice, compared untreated dental caries in established vs new MDI patient-visits. From 2019-2021, integrated DHs completed 13,458 visits to low-income patients, Medicaid (70%, n=9,421), uninsured (24%, n=3,230), SCHIP (3%, n=404), private (3%, n=404), of various ages: 0-5 (29%, n=3,838), 6-18 (17%, n=2,266), 18-64 (51%, n=6,825), >65 (4%, n=529). A total of 912 visits were provided to pregnant patients. Services included caries risk assessment (n=9,329), fluoride varnish (n=6,722), dental sealants (n=1,391), silver diamine fluoride (n=382), x-rays (n=5,465) and scaling/root-planing (n=2,882). Improvement was found in untreated decay of established vs. new patient-visits in four of the practices. Dental hygienists integrated into medical teams provided full-scope dental hygiene care to patients and expanded access to dental services. Medical-dental integration (MDI) care was variably associated with reduction in untreated decay. Integrating dental hygienists into primary care medical practices has potential to improve oral health-related outcomes, however access to restorative dental care remains a challenge.

A WIC-Based Behavior Change Intervention for Postpartum Women With Overweight and Obesity: A Pilot Feasibility Randomized Trial.

Background. Postpartum weight retention is a risk factor for obesity and is particularly important among Hispanic women who have an increased rate of obesity. Given its broad reach, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program provides an ideal setting to implement community-based interventions for low-income postpartum women. Purpose. To examine the feasibility, acceptability, and preliminary efficacy of a multicomponent intervention delivered by staff within the WIC program designed to promote behavior changes in urban, postpartum women with overweight/obesity. Method. This was a 12-week pilot trial randomizing participants to a health behavior change (Intervention) or control (Observation) group. The Intervention included monthly visits with trained WIC staff providing patient-centered behavior change counseling, with multiple touchpoints between visits promoting self-monitoring and offering health behavior change support. Results. Participants (n = 41), who were mainly Hispanic (n = 37, 90%) and Spanish-speaking (n = 33, 81%), were randomized to the Intervention (n = 19) or Observation (n = 22) group. In the Intervention group, 79% (n = 15) of eligible participants were retained for the study duration. All Intervention participants endorsed that they would participate again. Regarding physical activity, participant readiness to change and self-efficacy improved for Intervention participants. About one-quarter of women in the Intervention group (27%, n = 4) had a 5% weight loss compared with one woman (5%) in the Observation group; this difference was not statistically significant (p = .10). Conclusions. This pilot demonstrated the feasibility and acceptability of delivering a low-intensity behavior change intervention within the WIC setting for postpartum women with overweight/obesity. Findings support the role of WIC in addressing postpartum obesity.

The Impact of Altitude at Birth on Perinatal Respiratory Support for Neonates with Trisomy 21.

OBJECTIVE: Both high altitude and trisomy 21 (T21) status can negatively impact respiratory outcomes. The objective of this study was to examine the association between altitude and perinatal respiratory support in neonates with T21 compared with those without T21. STUDY DESIGN: This retrospective cohort study used the United States all-county natality files that included live, singleton, in-hospital births from 2015 to 2019. Descriptive statistics for neonates with and without the primary outcome of sustained assisted ventilation (>6 hours) were compared using t-tests and Chi-squared analyses. Multivariable logistic regression was used to determine the association between respiratory support and the presence of T21, and included an interaction term to determine whether the association between respiratory support and the presence of T21 was modified by elevation at delivery. RESULTS: A total of 17,939,006 neonates, 4,059 (0.02%) with T21 and 17,934,947 (99.98%) without, were included in the study. The odds of requiring sustained respiratory support following delivery were 5.95 (95% confidence interval [CI]: 5.31, 6.66), 4.06 (95% CI: 2.39, 6.89), 2.36 (95% CI: 1.64, 3.40), and 5.04 (95% CI: 1.54, 16.54) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevations, respectively. The odds of requiring immediate ventilation support following delivery were 5.01 (95% CI: 4.59, 5.46), 5.90 (95% CI: 4.16, 8.36), 2.86 (95% CI: 2.15, 3.80), and 12.08 (95% CI: 6.78, 21.51) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevation, respectively. CONCLUSION: Neonates with T21 have increased odds of requiring respiratory support following delivery when compared with neonates without T21 at all categories of altitude. However, the odds ratios did not increase monotonically with altitude which indicates additional research is critical in understanding the effects of altitude on neonates with T21. KEY POINTS: · Neonates with T21 have an increased need for perinatal respiratory support at all altitudes.. · The odds of needing perinatal respiratory support did not increase monotonically with elevation.. · Additional research is critical to understanding the effects of altitude on neonates with T21..

Multicenter Analysis of Cardiometabolic-related Diagnoses in Transgender and Gender-Diverse Youth: A PEDSnet Study.

CONTEXT: Studies on cardiometabolic health in transgender and gender-diverse youth (TGDY) are limited to small cohorts. OBJECTIVE: This work aimed to determine the odds of cardiometabolic-related diagnoses in TGDY compared to matched controls in a cross-sectional analysis, using a large, multisite database (PEDSnet). METHODS: Electronic health record data (2009-2019) were used to determine odds of cardiometabolic-related outcomes based on diagnosis, anthropometric, and laboratory data using logistic regression among TGDY youth vs controls. The association of gender-affirming hormone therapy (GAHT) with these outcomes was examined separately among TGDY. TGDY (n = 4172) were extracted from 6 PEDSnet sites and propensity-score matched on 8 variables to controls (n = 16 648). Main outcomes measures included odds of having cardiometabolic-related diagnoses among TGDY compared to matched controls, and among TGDY prescribed GAHT compared to those not prescribed GAHT. RESULTS: In adjusted analyses, TGDY had higher odds of overweight/obesity (1.2; 95% CI, 1.1-1.3) than controls. TGDY with a testosterone prescription alone or in combination with a gonadotropin-releasing hormone agonist (GnRHa) had higher odds of dyslipidemia (1.7; 95% CI, 1.3-2.3 and 3.7; 95% CI, 2.1-6.7, respectively) and liver dysfunction (1.5; 95% CI, 1.1-1.9 and 2.5; 95% CI, 1.4-4.3) than TGDY not prescribed GAHT. TGDY with a testosterone prescription alone had higher odds of overweight/obesity (1.8; 95% CI, 1.5-2.1) and hypertension (1.6 95% CI, 1.2-2.2) than those not prescribed testosterone. Estradiol and GnRHa alone were not associated with greater odds of cardiometabolic-related diagnoses. CONCLUSION: TGDY have increased odds of overweight/obesity compared to matched controls. Screening and tailored weight management, sensitive to the needs of TGDY, are needed.

Parent Attitudes Towards Childhood Vaccines After the Onset of SARS-CoV-2 in the United States.

OBJECTIVE: To understand the influence of a novel infectious disease epidemic on parent general attitudes about childhood vaccines. METHODS: We conducted a natural experiment utilizing cross-sectional survey data from parents of infants in Washington and Colorado participating in a larger trial that began on September 27, 2019. At enrollment, parents completed the short version of the Parental Attitudes about Childhood Vaccines (PACV-SF), a validated survey scored from 0 to 4, with higher scores representing more negative attitudes. The exposure variable was onset of the SARS-CoV-2 pandemic in the United States, with the before-period defined as September 27, 2019 to February 28, 2020 and the after-period defined as April 1, 2020-December 10, 2020, with the after-period further separated into proximate (April 1, 2020-July 31, 2020) and distant periods (August 1, 2020-December 10, 2020). The outcome variable was parent negative attitudes about childhood vaccines, defined as a score of ≥2 on the PACV-SF. We estimated the probability of the outcome after (vs before) the exposure using log-binomial regression with generalized estimating equations adjusted for demographic confounding variables. RESULTS: Among 4562 parents, the risk of negative attitudes was lower immediately after (vs before) SARS-CoV-2 onset (adjusted risk ratio [aRR] = 0.58; 95% confidence interval [CI], 0.36, 0.94; P = .027), but by August-December 2020, the average rate of negative attitudes was 35% higher than during April-July 2020 (aRR: 1.35; 95% CI: 1.13, 1.61; P = .0009). CONCLUSIONS: A reduced risk of negative general vaccine attitudes observed immediately after SARS-CoV-2 onset was quickly attenuated.

Hepatic abnormalities in youth with Turner syndrome.

BACKGROUND & AIMS: Liver disease in children with Turner Syndrome (TS) is poorly understood relative to associated growth, cardiac and reproductive complications. This study sought to better characterize hepatic abnormalities in a large national cohort of youth with TS. METHODS: Using electronic health record data from PEDSnet institutions, 2145 females with TS were matched to 8580 females without TS on eight demographic variables. Outcomes included liver enzymes (AST and ALT) stratified as normal, 1-2 times above the upper limit of normal (ULN), 2-3 times ULN and >3 times ULN, as well as specific liver disease diagnoses. RESULTS: Fifty-eight percent of youth with TS had elevated liver enzymes. Patients with TS had higher odds of enzymes 1-2 times ULN (OR: 1.7, 95% CI: 1.4-1.9), 2-3 times ULN (OR: 2.7, 95% CI: 1.7-3.3) and >3 times ULN (OR: 1.7, 95% CI: 1.3-2.2). They also had higher odds of any liver diagnosis (OR: 2.4, 95% CI: 1.7-3.3), fatty liver disease (OR: 1.9, 95% CI: 1.1-3.2), hepatitis (OR: 3.7, 95% CI: 1.9-7.1), cirrhosis/fibrosis (OR: 5.8, 95% CI: 1.3-25.0) and liver tumour/malignancy (OR: 4.8, 95% CI: 1.4-17.0). In a multinomial model, age, BMI and presence of cardiovascular disease or diabetes significantly increased the odds of elevated liver enzymes in girls with TS. CONCLUSIONS: Youth with TS have higher odds for elevated liver enzymes and clinically significant liver disease compared with matched controls. These results emphasize the need for clinical screening and additional research into the aetiology and treatment of liver disease in TS. LAY SUMMARY: Turner Syndrome, a chromosomal condition in which females are missing the second sex chromosome, is often associated with short stature, infertility and cardiac complications. Liver abnormalities are less well described in the literature. In this study, nearly 60% of youth with TS have elevated liver enzymes. Furthermore, patients with TS had a diagnosis of liver disease more often than patients without TS. Our results support the importance of early and consistent liver function screening and of additional research to define mechanisms that disrupt liver function in paediatric TS females.

Population-based Assessment of Cardiometabolic-related Diagnoses in Youth With Klinefelter Syndrome: A PEDSnet Study.

CONTEXT: Diabetes and cardiovascular diseases are common among men with Klinefelter syndrome (KS) and contribute to high morbidity and mortality. OBJECTIVE: To determine if cardiometabolic-related diagnoses are more prevalent among youth with KS than matched controls in a large population-based cohort. METHODS: Secondary data analysis of electronic health records from 6 pediatric institutions in the United States (PEDSnet). Patients included all youth with KS in the database (n = 1080) and 4497 youth without KS matched for sex, age (mean 13 years at last encounter), year of birth, race, ethnicity, insurance, site, and duration of care (mean 7 years). The main outcome measures were prevalence of 5 cardiometabolic-related outcomes: overweight/obesity, dyslipidemia, dysglycemia, hypertension, and liver dysfunction. RESULTS: The odds of overweight/obesity (OR 1.6; 95% CI 1.4-1.8), dyslipidemia (3.0; 2.2-3.9), and liver dysfunction (2.0; 1.6-2.5) were all higher in KS than in controls. Adjusting for covariates (obesity, testosterone treatment, and antipsychotic use) attenuated the effect of KS on these outcomes; however, boys with KS still had 45% greater odds of overweight/obesity (95% CI 1.2-1.7) and 70% greater odds of liver dysfunction (95% CI 1.3-2.2) than controls, and both dyslipidemia (1.6; 1.1-2.4) and dysglycemia (1.8; 1.1-3.2) were higher in KS but of borderline statistical significance when accounting for multiple comparisons. The odds of hypertension were not different between groups. CONCLUSION: This large, population-based cohort of youth with KS had a higher odds of most cardiometabolic-related diagnoses than matched controls.

Rare coding variants in RCN3 are associated with blood pressure.

BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries. RESULTS: Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10- 7). CONCLUSIONS: Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.

Behavioral Health Diagnoses in Youth with Gender Dysphoria Compared with Controls: A PEDSnet Study.

OBJECTIVE: To assess the odds of a psychiatric or neurodevelopmental diagnosis among youth with a diagnosis of gender dysphoria compared with matched controls in a large electronic health record dataset from 6 pediatric health systems, PEDSnet. We hypothesized that youth with gender dysphoria would have higher odds of having psychiatric and neurodevelopmental diagnoses than controls. STUDY DESIGN: All youth with a diagnosis of gender dysphoria (n = 4173 age at last visit 16.2 ± 3.4) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables to controls without gender dysphoria (n = 16 648, age at last visit 16.2 ± 4.8) using multivariable logistic regression. The odds of having psychiatric and neurodevelopmental diagnoses were examined using generalized estimating equations. RESULTS: Youth with gender dysphoria had higher odds of psychiatric (OR 4.0 [95% CI 3.8, 4.3] P < .0001) and neurodevelopmental diagnoses (1.9 [1.7, 2.0], P < .0001). Youth with gender dysphoria were more likely to have a diagnosis across all psychiatric disorder subcategories, with particularly high odds of mood disorder (7.3 [6.8, 7.9], P < .0001) and anxiety (5.5 [5.1, 5.9], P < .0001). Youth with gender dysphoria had a greater odds of autism spectrum disorder (2.6, [2.2, 3.0], P < .0001). CONCLUSIONS: Youth with gender dysphoria at large pediatric health systems have greater odds of psychiatric and several neurodevelopmental diagnoses compared with youth without gender dysphoria. Further studies are needed to evaluate changes in mental health over time with access to gender affirming care.

Assessing and Augmenting Predictive Models for Hospital Readmissions With Novel Variables in an Urban Safety-net Population.

BACKGROUND: The performance of existing predictive models of readmissions, such as the LACE, LACE+, and Epic models, is not established in urban safety-net populations. We assessed previously validated predictive models of readmission performance in a socially complex, urban safety-net population, and if augmentation with additional variables such as the Area Deprivation Index, mental health diagnoses, and housing access improves prediction. Through the addition of new variables, we introduce the LACE-social determinants of health (SDH) model. METHODS: This retrospective cohort study included adult admissions from July 1, 2016, to June 30, 2018, at a single urban safety-net health system, assessing the performance of the LACE, LACE+, and Epic models in predicting 30-day, unplanned rehospitalization. The LACE-SDH development is presented through logistic regression. Predictive model performance was compared using C-statistics. RESULTS: A total of 16,540 patients met the inclusion criteria. Within the validation cohort (n=8314), the Epic model performed the best (C-statistic=0.71, P<0.05), compared with LACE-SDH (0.67), LACE (0.65), and LACE+ (0.61). The variables most associated with readmissions were (odds ratio, 95% confidence interval) against medical advice discharge (3.19, 2.28-4.45), mental health diagnosis (2.06, 1.72-2.47), and health care utilization (1.94, 1.47-2.55). CONCLUSIONS: The Epic model performed the best in our sample but requires the use of the Epic Electronic Health Record. The LACE-SDH performed significantly better than the LACE and LACE+ models when applied to a safety-net population, demonstrating the importance of accounting for socioeconomic stressors, mental health, and health care utilization in assessing readmission risk in urban safety-net patients.

Rural Adolescent Immunization: Delivery Practices and Barriers to Uptake.

BACKGROUND: Rural adolescent vaccination rates lag behind urban. We sought to assess rural-urban differences in barriers to adolescent vaccination, perceived parental vaccine attitudes, and immunization delivery practices among public health nursing (PHN), pediatric (Peds), and family medicine (FM) clinicians. METHODS: Internet and mail survey of Colorado PHN, Peds, and FM clinicians from June-August 2019. Study population was recruited from local health plans and the American Medical Association Physician Masterfile. Rural and urban responses were compared using Cochran Armitage trend, Fisher's exact, and chi-square tests. RESULTS: Response rate was 38% (163/433; 91 rural, 72 urban). Rural respondents were less likely than urban to agree most patients have insurance that covers vaccination (86% vs 97%; P = .02). Rural respondents were less likely than urban to indicate most parents in their practice would agree with statements about vaccine benefits (P = .02) and trust in medical providers (P = .05). Rural respondents were more likely than urban to report adolescents were somewhat/very likely to receive vaccines at public health departments (65% vs 28%; P < .0001) and less likely to report adolescents were somewhat/very likely to receive vaccines at pharmacies (26% vs 45%; P = .02). Fewer providers strongly recommended HPV vaccine (81% for females, 80% for males 11 to 12 years) than other adolescent immunizations (Tdap: 97%, MenACWY at 11 to 12 years: 87%; influenza at 11 to 17 years: 87%; each P < .005, rural-urban responses did not differ). CONCLUSIONS: Rural barriers to adolescent vaccination include logistic issues and parental vaccine attitudes. Efforts to improve rural adolescent vaccination should include public health departments and address vaccine confidence and access barriers.

Behavioral Health Diagnoses in Youth with Differences of Sex Development or Congenital Adrenal Hyperplasia Compared with Controls: A PEDSnet Study.

OBJECTIVE: To evaluate the odds of a behavioral health diagnosis among youth with differences of sex development (DSD) or congenital adrenal hyperplasia (CAH) compared with matched controls in the PEDSnet database. STUDY DESIGN: All youth with a diagnosis of DSD (n = 1216) or CAH (n = 1647) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables (1:4) with controls (n = 4864 and 6588, respectively) using multivariable logistic regression. The likelihood of having behavioral health diagnoses was examined using generalized estimating equations. RESULTS: Youth with DSD had higher odds of a behavioral health diagnosis (OR, 1.7; 95% CI, 1.4-2.1; P < .0001) and neurodevelopmental diagnosis (OR, 1.7; 95% CI, 1.4, 2.0; P < .0001) compared with matched controls. Youth with CAH did not have an increased odds of a behavioral health diagnosis (OR, 1.0; 95% CI, 0.9, 1.1; P = .9) compared with matched controls but did have higher odds of developmental delay (OR, 1.8; 95% CI, 1.4, 2.4; P < .0001). CONCLUSIONS: Youth with DSD diagnosis have higher odds of a behavioral health or neurodevelopmental diagnosis compared with matched controls. Youth with CAH have higher odds of developmental delay, highlighting the need for screening in both groups.

Transmission of Intergenerational Parenting Attitudes and Natural Mentorship: Associations Within the LONGSCAN population.

BACKGROUND: Evidence suggests that families transmit child maltreatment and parenting attitudes. Natural mentorship may mediate intergenerational parenting attitudes' risk for maltreatment but has not been studied. OBJECTIVE: To compare parenting attitudes between adolescents exposed to or at risk for maltreatment and their caregivers and to determine if natural mentorship mediates differences in parenting attitudes' maltreatment risk. PARTICIPANTS AND SETTING: The study included 779 children and their caregivers from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) study, METHODS: Standardized measures assessed parenting attitudes, natural mentorship and demographic characteristics. Repeated measures, multivariable logistic regressions were used to predict low risk parenting attitudes for maltreatment among adolescents with and without natural mentors. RESULTS: In adjusted analysis, natural mentorship did not predict an adolescent having low risk parenting attitudes when their caregivers had moderate or high risk attitudes: appropriate empathy adjusted odds ratio [aOR] = 1.26; 95% confidence interval [CI] 0.52 -3.01; appropriate expectations aOR = 1.35; CI 0.62-2.93; physical punishment rejection aOR = 1.74; CI 0.78-3.88; and appropriate roles aOR = 1.11; CI 0.57-2.18. Low risk caregiver parenting attitudes for appropriate empathy related to adolescents having low risk empathy attitudes (aOR = 2.89; CI 1.31-6.37). Male gender, African American race and Hispanic ethnicity were negatively associated with an adolescent having low risk parenting attitudes for maltreatment. CONCLUSIONS: Natural mentorship did not mediate adolescent parenting attitudes. While prevention and intervention strategies should include natural mentoring given positive health impacts, services must be cognizant of and designed for gender, racial and ethnic diversity.

Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data.

In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p < 0.05). One of the genes is RBFOX1, an evolutionarily conserved RNA-binding protein that regulates tissue-specific alternative splicing that we previously reported to be associated with BP using exome array data in CFS. After follow-up analysis of the 25 genes in ten independent TOPMed studies with individuals of European, African, and East Asian ancestry, and Hispanics (N = 29,988), we identified variants in SLX4 (p = 2.19 × 10-4) to be significantly associated with BP traits when accounting for multiple testing. We also replicated the associations previously reported for RBFOX1 (p = 0.007). Follow-up analysis with GTEx eQTL data shows SLX4 variants are associated with gene expression in coronary artery, multiple brain tissues, and right atrial appendage of the heart. Our study demonstrates that linkage analysis of family data can provide an efficient approach for detecting rare variants associated with complex traits in WGS data.

Delays in Diagnosis and Treatment of Breast Cancer: A Safety-Net Population Profile.

Background: Timely detection and treatment of breast cancer is important in optimizing survival and minimizing recurrence. Given disparities in breast cancer outcomes based on socioeconomic status, we examined time to diagnosis and treatment in a safety-net hospital. Methods: We conducted a retrospective review of all patients with breast cancer diagnosed between July 1, 2010, and June 30, 2012 (N=120). We limited our analytic sample to patients with nonrecurrent, primary stage 0-III breast cancer (N=105) and determined intervals from presentation to diagnosis, diagnosis to first treatment, last surgery to chemotherapy initiation, and last surgery to start of radiation therapy (RT). Using logistic regression, we calculated unadjusted odds of receiving timely treatment (< median time) versus more delayed treatment (≥ median time) as a function of age, language, ethnicity, insurance, Charlson comorbidity index, disease stage, method of first presentation (screening mammography vs care provider), symptoms at presentation, and type of surgical treatment. Results: Patients aged 55 to 64 years accounted for most of the sample (n=37; 35.2%). Median time from presentation to diagnosis (23 days), time from diagnosis to first treatment, and time from surgery to chemotherapy initiation fell within intervals published in the literature; median time from last surgery to start of RT was greater than recommended intervals. Factors significantly associated with longer intervals than median time included stage, method of presentation, language, surgical treatment, insurance, and ethnicity. Conclusions: Patients in this safety-net setting experienced acceptable diagnosis and treatment intervals, except for time to RT. Focused interventions that help care providers access imaging quickly for their symptomatic patients could improve time to diagnosis. Concentrating additional efforts on non-English-speaking, Hispanic patients and those who need to receive RT could improve time to treatment.

Timing of Information-Seeking about Infant Vaccines.

OBJECTIVES: To assess among pregnant and recently delivered women the timing of thinking about and seeking information about childhood vaccines and the preferred modes of vaccine education. STUDY DESIGN: An e-mail survey among women in 9 urban and rural obstetrics practices in Colorado was conducted from February to April 2014, timed so that approximately one-half had delivered and one-half were still pregnant, designed to assess the frequency of thinking about and seeking information about vaccines in relation to estimated or actual delivery date. A shortened version of the Parental Attitudes About Childhood Vaccines scale was used to assess vaccine hesitancy. RESULTS: The response rate was 54% (230 of 425); 56% were pregnant, 44% had delivered, and 18% were vaccine-hesitant. Compared with pregnant women, women who had delivered more often reported thinking about vaccines for their infant (pregnant: 19% often, 42% sometimes; delivered: 29% often, 51% sometimes; P < .05) and looking for information about vaccines (pregnant: 6% often, 22% sometimes; delivered: 16% often, 34% sometimes; P < .01). Women most frequently reported seeking information about vaccines 2-4 weeks after delivery, followed by 4-6 weeks after delivery. The most preferred method for vaccine education was their child's doctor (95% acceptable; 92% likely to use) followed by their obstetrician (79% acceptable; 64% likely to use). CONCLUSIONS: Within 6 weeks postdelivery appears to be when the most women seek vaccine information. A child's doctor remains the most acceptable source of vaccine education.

Exploring Facilitators and Barriers to Initiation and Completion of the Human Papillomavirus (HPV) Vaccine Series among Parents of Girls in a Safety Net System.

Objective: To assess, among parents of predominantly minority, low-income adolescent girls who had either not initiated (NI) or not completed (NC) the HPV vaccine series, attitudes and other factors important in promoting the series, and whether attitudes differed by language preference. Design/Methods: From August 2013-October 2013, we conducted a mail survey among parents of girls aged 12-15 years randomly selected from administrative data in a Denver safety net system; 400 parents from each group (NI and NC) were targeted. Surveys were in English or Spanish. RESULTS: The response rate was 37% (244/660; 140 moved or gone elsewhere; 66% English-speaking, 34% Spanish-speaking). Safety attitudes of NIs and NCs differed, with 40% NIs vs. 14% NC's reporting they thought HPV vaccine was unsafe (p < 0.0001) and 43% NIs vs. 21% NCs that it may cause long-term health problems (p < 0.001). Among NCs, 42% reported they did not know their daughter needed more shots (English-speaking, 20%, Spanish-speaking 52%) and 39% reported that "I wasn't worried about the safety of the HPV vaccine before, but now I am" (English-speaking, 23%, Spanish-speaking, 50%). Items rated as very important among NIs in the decision regarding vaccination included: more information about safety (74%), more information saying it prevents cancer (70%), and if they knew HPV was spread mainly by sexual contact (61%). Conclusions: Safety concerns, being unaware of the need for multiple doses, and low perceived risk of infection remain significant barriers to HPV vaccination for at-risk adolescents. Some parents' safety concerns do not appear until initial vaccination.