Increased Muc5AC and Decreased Ciliated Cells in Severe Asthma Partially Restored by Inhibition of IL-4Rα Receptor.

BACKGROUND: The role of IL-13 on the airway epithelium in severe asthma leading to airway remodeling remains poorly understood. OBJECTIVE: To study IL-13 induced airway remodeling on goblet cells and cilia in the airway epithelium in severe asthma and the impact of an anti-IL4Rα antibody, dupilumab, in vitro. METHODS: Quantitative CT (qCT) lungs and endobronchial biopsies and brushings were obtained in 51 participants (22 severe, 11 non-severe asthma and 18 healthy participants) in the Severe Asthma Research Program (SARPIII) and measured for mucin and cilia related proteins. Epithelial cells were differentiated in air-liquid interphase (ALI) with IL-13 +/-dupilumab and assessed for mucin, cilia, cilia beat frequency (CBF) and epithelial integrity (transepithelial electrical resistance, TEER). RESULTS: Increased Muc5AC (Δ+263.2±92.7 lums/EpiArea) and decreased ciliated cells (Δ-0.07±0.03 Foxj1+cells/EpiArea) were observed in biopsies from severe asthma when compared to healthy (p<0.01 and p=0.047 respectively). RNAseq of epithelial cell brushes confirmed a Muc5AC increase with a decrease in a 5-gene cilia-related mean in severe asthma compared to healthy (all p<0.05). IL-13 (5 ng/mL) differentiated ALI cultures of healthy and asthmatic (severe and non-severe participants) increased Muc5AC, decreased cilia (α-acytl-tubulin) in healthy (Δ+6.5±1.5%, Δ-14.1±2.7%; all p<0.001 respectively) and asthma (Δ+4.4±2.5%, Δ-13.1±2.7%; p=0.084, p<0.001 respectively); decreased epithelial integrity (TEER) in healthy (-140.9±21.3 [ohms], p<0.001) while decreasing CBF in asthma (Δ-4.4±1.7 [Hz], p<0.01). When dupilumab was added to ALI with IL-13, there was no significant decrease in Mu5AC but there was restoration of cilia in healthy and asthma participants (absolute increase of 67.5% and 32.5% cilia, all p<0.05 respectively) while CBF increased (Δ+3.6±1.1 [Hz], p<0.001) and TEER decreased (only in asthma Δ-37.8±16.2 [ohms] p<0.05). CONCLUSIONS: IL-13 drives features of airway remodeling in severe asthma which are partially reversed by inhibiting IL-4Rα receptor in vitro.

Incidence of and Factors Associated With Recurrent Firearm Injury Among Patients Presenting to St. Louis Trauma Centers, 2010 to 2019 : A Cohort Study.

BACKGROUND: Firearm injuries are a public health crisis in the United States. OBJECTIVE: To examine the incidence and factors associated with recurrent firearm injuries and death among patients presenting with an acute (index), nonfatal firearm injury. DESIGN: Multicenter, observational, cohort study. SETTING: Four adult and pediatric level I trauma hospitals in St. Louis, Missouri, 2010 to 2019. PARTICIPANTS: Consecutive adult and pediatric patients (n = 9553) presenting to a participating hospital with a nonfatal acute firearm injury. MEASUREMENTS: Data on firearm-injured patient demographics, hospital and diagnostic information, health insurance status, and death were collected from the St. Louis Region-Wide Hospital-Based Violence Intervention Program Data Repository. The Centers for Disease Control and Prevention (CDC) Social Vulnerability Index was used to characterize the social vulnerability of the census tracts of patients' residences. Analysis included descriptive statistics and time-to-event analyses estimating the probability of experiencing a recurrent firearm injury. RESULTS: We identified 10 293 acutely firearm-injured patients of whom 9553 survived the injury and comprised the analytic sample. Over a median follow-up of 3.5 years (IQR, 1.5 to 6.4 years), 1155 patients experienced a recurrent firearm injury including 5 firearm suicides and 149 fatal firearm injuries. Persons experiencing recurrent firearm injury were young (25.3 ± 9.5 years), predominantly male (93%), Black (96%), and uninsured (50%), and resided in high social vulnerability regions (65%). The estimated risk for firearm reinjury was 7% at 1 year and 17% at 8 years. LIMITATIONS: Limited data on comorbidities and patient-level social determinants of health. Inability to account for recurrent injuries presenting to nonstudy hospitals. CONCLUSION: Recurrent injury and death are frequent among survivors of firearm injury, particularly among patients from socially vulnerable areas. Our findings highlight the need for interventions to prevent recurrence. PRIMARY FUNDING SOURCE: Emergency Medicine Foundation-AFFIRM and Missouri Foundation for Health.

Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization.

OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

A systematic review of recurrent firearm injury rates in the United States.

OBJECTIVES: To conduct a systematic review of methodologies, data sources, and best practices for identifying, calculating, and reporting recurrent firearm injury rates in the United States. METHODS: In accordance with PRISMA guidelines, we searched seven electronic databases on December 16, 2021, for peer-reviewed articles that calculated recurrent firearm injury in generalizable populations. Two reviewers independently assessed the risk of bias, screened the studies, extracted data, and a third resolved conflicts. FINDINGS: Of the 918 unique articles identified, 14 met our inclusion criteria and reported recurrent firearm injury rates from 1% to 9.5%. We observed heterogeneity in study methodologies, including data sources utilized, identification of subsequent injury, follow-up times, and the types of firearm injuries studied. Data sources ranged from single-site hospital medical records to comprehensive statewide records comprising medical, law enforcement, and social security death index data. Some studies applied machine learning to electronic health records to differentiate subsequent new firearm injuries from the index injury, while others classified all repeat firearm-related hospital admissions after variably defined cut-off times as a new injury. Some studies required a minimum follow-up observation period after the index injury while others did not. Four studies conducted survival analyses, albeit using different methodologies. CONCLUSIONS: Variability in both the data sources and methods used to evaluate and report recurrent firearm injury limits individual study generalizability of individual and societal factors that influence recurrent firearm injury. Our systematic review highlights the need for development, dissemination, and implementation of standard practices for calculating and reporting recurrent firearm injury.

Family-Based Behavioral Treatment for Childhood Obesity Implemented in Pediatric Primary Care: A Randomized Clinical Trial.

Importance: Intensive behavioral interventions for childhood overweight and obesity are recommended by national guidelines, but are currently offered primarily in specialty clinics. Evidence is lacking on their effectiveness in pediatric primary care settings. Objective: To evaluate the effects of family-based treatment for overweight or obesity implemented in pediatric primary care on children and their parents and siblings. Design, Setting, and Participants: This randomized clinical trial in 4 US settings enrolled 452 children aged 6 to 12 years with overweight or obesity, their parents, and 106 siblings. Participants were assigned to undergo family-based treatment or usual care and were followed up for 24 months. The trial was conducted from November 2017 through August 2021. Interventions: Family-based treatment used a variety of behavioral techniques to develop healthy eating, physical activity, and parenting behaviors within families. The treatment goal was 26 sessions over a 24-month period with a coach trained in behavior change methods; the number of sessions was individualized based on family progress. Main Outcomes and Measures: The primary outcome was the child's change from baseline to 24 months in the percentage above the median body mass index (BMI) in the general US population normalized for age and sex. Secondary outcomes were the changes in this measure for siblings and in BMI for parents. Results: Among 452 enrolled child-parent dyads, 226 were randomized to undergo family-based treatment and 226 to undergo usual care (child mean [SD] age, 9.8 [1.9] years; 53% female; mean percentage above median BMI, 59.4% [n = 27.0]; 153 [27.2%] were Black and 258 [57.1%] were White); 106 siblings were included. At 24 months, children receiving family-based treatment had better weight outcomes than those receiving usual care based on the difference in change in percentage above median BMI (-6.21% [95% CI, -10.14% to -2.29%]). Longitudinal growth models found that children, parents, and siblings undergoing family-based treatment all had outcomes superior to usual care that were evident at 6 months and maintained through 24 months (0- to 24-month changes in percentage above median BMI for family-based treatment and usual care were 0.00% [95% CI, -2.20% to 2.20%] vs 6.48% [95% CI, 4.35%-8.61%] for children; -1.05% [95% CI, -3.79% to 1.69%] vs 2.92% [95% CI, 0.58%-5.26%] for parents; and 0.03% [95% CI, -3.03% to 3.10%] vs 5.35% [95% CI, 2.70%-8.00%] for siblings). Conclusions and Relevance: Family-based treatment for childhood overweight and obesity was successfully implemented in pediatric primary care settings and led to improved weight outcomes over 24 months for children and parents. Siblings who were not directly treated also had improved weight outcomes, suggesting that this treatment may offer a novel approach for families with multiple children. Trial Registration: ClinicalTrials.gov Identifier: NCT02873715.

Understanding community- and system-capacity change over time: A close look at changing social capital in Evidence2Success communities.

Evidence in majority White and low-population areas suggest that community prevention systems can create social capital that is needed to support high-quality implementation and sustainability of evidence-based programs. This study expands prior work by asking the question: How does community social capital change during the implementation of a community prevention system in low-income, highly populated communities of color? Data were collected from Community Board members and Key Leaders in five communities. Linear mixed effect models analyzed data on reports of social capital over time, first as reported by Community Board members then by Key Leaders. Community Board members reported social capital improved significantly over time during the implementation of the Evidence2Success framework. Key Leader reports did not change significantly over time. These findings suggest that community prevention systems implemented in historically marginalized communities may help communities build social capital that is likely to support the dissemination and sustainability of evidence-based programs.

Resilience among racially diverse adolescent patients with chronic orthopedic conditions.

The theoretical literature on resilience shows there is no consensus regarding whether resilience is an ability; interactive process involving the individual, group, and community; both ability and process; or favorable outcome. A definitive part of the research on children's resilience featured the assessment of an indicator of resilience (e.g., health-related quality of life) and involved pediatric patients with prolonged illnesses. The present study examined resilience directly as an ability and process, and related protective or risk variables, with validated instruments among adolescent patients with chronic orthopedic conditions. One-hundred fifteen adolescent patients assented (parents/legally authorized representatives consented), with 73 completing the study questionnaire. Fifteen, 47, and 10 scored low, normal, or high, respectively, on resilience-ability (one with missing data). These three groups differed significantly on the number of years living with family, individual personal skills, self-esteem, negative affect, anxiety, and depression. Resilience-ability positively correlated with number of years living with family, individual personal skills, and self-esteem, but negatively with duration of chronic orthopedic condition, negative affect, anxiety, and depression. Duration of chronic orthopedic condition negatively correlated with individual peer support among those scoring high on resilience-ability. For girls, duration of chronic orthopedic condition negatively correlated with resilience-ability, educational context, and self-esteem, but positively correlated with caregiver physical and psychological caregiving for boys. Findings underscored the consequence of resilience for these adolescent patients, with their chronic orthopedic conditions affecting daily function and life quality. Implementation of best practices to nurture and enhance their health-related resilience will promote a lifetime of well-being.

Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d'Ivoire.

BACKGROUND: Ivermectin (IVM) plus albendazole (ALB), or IA, is widely used in mass drug administration (MDA) programs that aim to eliminate lymphatic filariasis (LF) in Africa. However, IVM can cause severe adverse events in persons with heavy Loa loa infections that are common in Central Africa. ALB is safe in loiasis, but more information is needed on its efficacy for LF. This study compared the efficacy and safety of 3 years of semiannual treatment with ALB to annual IA in persons with bancroftian filariasis. METHODS: Adults with Wuchereria bancrofti microfilaremia (Mf) were randomized to receive either 3 annual doses of IA (N = 52), 6 semiannual doses of ALB 400 mg (N = 45), or 6 semiannual doses of ALB 800 mg (N = 47). The primary outcome is amicrofilaremia at 36 months. RESULTS: IA was more effective for completely clearing Mf than ALB 400mg or ALB 800mg (79%, 95% confidence interval [CI]: 67-91; vs 48%, 95% CI: 32-66 and 57%, 95% CI: 41-73, respectively). Mean percentage reductions in Mf counts at 36 months relative to baseline tended to be greater after IA (98%, 95% CI: 88-100) than after ALB 400 mg (88%, 95% CI: 78-98) and ALB 800 mg (89%, 95% CI: 79-99) (P = .07 and P = .06, respectively). Adult worm nest numbers (assessed by ultrasound) were reduced in all treatment groups. Treatments were well tolerated. CONCLUSIONS: Repeated semiannual treatment with ALB is macrofilaricidal for W. bancrofti and leads to sustained reductions in Mf counts. This is a safe and effective regimen that could be used as MDA to eliminate LF in areas where ivermectin cannot be used. CLINICAL TRIALS REGISTRATION: NCT02974049.

Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts.

Background Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes. Purpose To determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes. Materials and Methods A retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models. Results A total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P < .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P < .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P < .001). Conclusion Quantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.

Temporal Associations Between EHR-Derived Workload, Burnout, and Errors: a Prospective Cohort Study.

BACKGROUND: The temporal progression and workload-related causal contributors to physician burnout are not well-understood. OBJECTIVE: To characterize burnout's time course and evaluate the effect of time-varying workload on burnout and medical errors. DESIGN: Six-month longitudinal cohort study with measurements of burnout, workload, and wrong-patient orders every 4 weeks. PARTICIPANTS: Seventy-five intern physicians in internal medicine, pediatrics, and anesthesiology at a large academic medical center. MAIN MEASURES: Burnout was measured using the Professional Fulfillment Index survey. Workload was collected from electronic health record (EHR) audit logs and summarized as follows: total time spent on the EHR, after-hours EHR time, patient load, inbox time, chart review time, note-writing time, and number of orders. Wrong-patient orders were assessed using retract-and-reorder events. KEY RESULTS: Seventy-five of 104 interns enrolled (72.1%) in the study. A total of 337 surveys and 8,863,318 EHR-based actions were analyzed. Median burnout score across the cohort across all time points was 1.2 (IQR 0.7-1.7). Individual-level burnout was variable (median monthly change 0.3, IQR 0.1-0.6). In multivariable analysis, increased total EHR time (ß=0.121 for an increase from 54.5 h per month (25th percentile) to 123.0 h per month (75th percentile), 95%CI=0.016-0.226), increased patient load (ß=0.130 for an increase from 4.9 (25th percentile) to 7.1 (75th percentile) patients per day, 95%CI=0.053-0.207), and increased chart review time (ß=0.096 for an increase from 0.39 (25th percentile) to 0.59 (75th percentile) hours per patient per day, 95%CI=0.015-0.177) were associated with an increased burnout score. After adjusting for the total number of ordering sessions, burnout was not statistically associated with an increased rate of wrong-patient orders (rate ratio=1.20, 95%CI=0.76-1.89). CONCLUSIONS: Burnout and recovery were associated with recent clinical workload for a cohort of physician trainees, highlighting the elastic nature of burnout. Wellness interventions should focus on strategies to mitigate sustained elevations of work responsibilities.

Quantitative CT metrics are associated with longitudinal lung function decline and future asthma exacerbations: Results from SARP-3.

BACKGROUND: Currently, there is limited knowledge regarding which imaging assessments of asthma are associated with accelerated longitudinal decline in lung function. OBJECTIVES: We aimed to assess whether quantitative computed tomography (qCT) metrics are associated with longitudinal decline in lung function and morbidity in asthma. METHODS: We analyzed 205 qCT scans of adult patients with asthma and calculated baseline markers of airway remodeling, lung density, and pointwise regional change in lung volume (Jacobian measures) for each participant. Using multivariable regression models, we then assessed the association of qCT measurements with the outcomes of future change in lung function, future exacerbation rate, and changes in validated measurements of morbidity. RESULTS: Greater baseline wall area percent (ß = -0.15 [95% CI = -0.26 to -0.05]; P < .01), hyperinflation percent (ß = -0.25 [95% CI = -0.41 to -0.09]; P < .01), and Jacobian gradient measurements (cranial-caudal ß = 10.64 [95% CI = 3.79-17.49]; P < .01; posterior-anterior ß = -9.14, [95% CI = -15.49 to -2.78]; P < .01) were associated with more severe future lung function decline. Additionally, greater wall area percent (rate ratio = 1.06 [95% CI = 1.01-1.10]; P = .02) and air trapping percent (rate ratio =1.01 [95% CI = 1.00-1.02]; P = .03), as well as lower decline in the Jacobian determinant mean (rate ratio = 0.58 [95% CI = 0.41-0.82]; P < .01) and Jacobian determinant standard deviation (rate ratio = 0.52 [95% CI = 0.32-0.85]; P = .01), were associated with a greater rate of future exacerbations. However, imaging metrics were not associated with clinically meaningful changes in scores on validated asthma morbidity questionnaires. CONCLUSIONS: Baseline qCT measures of more severe airway remodeling, more small airway disease and hyperinflation, and less pointwise regional change in lung volumes were associated with future lung function decline and asthma exacerbations.

Lung function trajectories and bronchial hyperresponsiveness during childhood following severe RSV bronchiolitis in infancy.

BACKGROUND: Children with severe respiratory syncytial virus (RSV) bronchiolitis in infancy have increased risks of asthma and reduced lung function in later life. There are limited studies on the longitudinal changes of lung function and bronchial hyperreactivity from early to late childhood in infants hospitalized for RSV bronchiolitis. METHODS: In a prospective cohort of 206 children with their first episode of RSV-confirmed bronchiolitis in the first year of life, 122 had spirometry performed at least twice between 5-16 years of age. Methacholine bronchoprovocation was available in 127 and 79 children at 7 and 12 years of age, respectively. Longitudinal changes in FEV1 , FVC, and FEV1 /FVC z-scores and methacholine PC20 were analyzed. RESULTS: 55% of the study cohort (N = 122) were male, and 55% were Caucasian. During follow-up, longitudinal changes in z-scores for pre- and post-bronchodilator FEV1 (P < .0001) FVC (P < .0001) and FEV1 /FVC (P < .0001 for pre- and 0.007 for post-bronchodilator) from age 5 to 10-16 years were observed. Declined lung function in late childhood was significantly associated with gender, physician diagnosis of asthma, and allergic sensitization. PC20 geometric mean increased from 0.28 mg/mL at 7 years to 0.53 mg/mL at 12 years of age, and the frequency of abnormal bronchial hyperreactivity decreased from 96% to 78% (P = .0003). CONCLUSIONS: Following severe RSV bronchiolitis, there appear to be significant longitudinal changes in pre- and post-bronchodilator lung function during childhood. The study has several limitations including significant dropouts and the lack of a control group and post-bronchodilator measurements. Bronchial hyperreactivity is common in children following severe RSV bronchiolitis; however, it appears to decrease as they enter late childhood.

Single-Session Bronchial Thermoplasty Guided by 129Xe Magnetic Resonance Imaging. A Pilot Randomized Controlled Clinical Trial.

Rationale: Adverse events have limited the use of bronchial thermoplasty (BT) in severe asthma.Objectives: We sought to evaluate the effectiveness and safety of using 129Xe magnetic resonance imaging (129Xe MRI) to prioritize the most involved airways for guided BT.Methods: Thirty subjects with severe asthma were imaged with volumetric computed tomography and 129Xe MRI to quantitate segmental ventilation defects. Subjects were randomized to treatment of the six most involved airways in the first session (guided group) or a standard three-session BT (unguided). The primary outcome was the change in Asthma Quality of Life Questionnaire score from baseline to 12 weeks after the first BT for the guided group compared with after three treatments for the unguided group.Measurements and Main Results: There was no significant difference in quality of life after one guided compared with three unguided BTs (change in Asthma Quality of Life Questionnaire guided = 0.91 [95% confidence interval, 0.28-1.53]; unguided = 1.49 [95% confidence interval, 0.84-2.14]; P = 0.201). After one BT, the guided group had a greater reduction in the percentage of poorly and nonventilated lung from baseline when compared with unguided (-17.2%; P = 0.009). Thirty-three percent experienced asthma exacerbations after one guided BT compared with 73% after three unguided BTs (P = 0.028).Conclusions: Results of this pilot study suggest that similar short-term improvements can be achieved with one BT treatment guided by 129Xe MRI when compared with standard three-treatment-session BT with fewer periprocedure adverse events.

Testing the Feasibility of Using Ecological Momentary Assessment to Collect Real-Time Behavior and Mood to Predict Technology-Measured HIV Medication Adherence.

Identifying distinct patterns of behavior and mood in natural environments that interrupt medication adherence among individuals with HIV will be useful in informing intervention development. This pilot study assessed the initial efficacy of using ecologic momentary assessment to define patterns of alcohol use, mood, and medication adherence. Participants reported intraday alcohol use and mood using app-enabled smartphones and MEMSCap pill bottles to measure medication adherence. There were 34 enrolled participants, 29 of whom completed the 28-day study. Participants drank a mean of 7.75 days of the study period. The positive and negative affect scores ranged from 10 to 50, with a mean of 25.7 and 11.4 for each, respectively. The average medication adherence for the sample was 94.1%. These findings suggest these types of data collection methods are increasingly acceptable in measuring real-time mood and behavior, which may better inform interventions addressed at increasing HIV adherence practices.

Public Health Benefits 16 Years After a Statewide Policy Change: Communities That Care in Pennsylvania.

Communities That Care (CTC), an evidence-based prevention system, has been installed outside of a research context in over 500 communities worldwide. Yet, its effectiveness in a non-research context is unknown. Using a repeated cross-sectional design with propensity score weighting at the school district-level, the purpose of this study was to examine the effect of widespread diffusion of CTC across Pennsylvania on adolescent substance use, delinquency, and depression. Anonymous youth survey data were collected from 6th, 8th, 10th, and 12th grade students every other year from 2001 to 2011. Three-hundred eighty-eight school districts participated in one to six waves of data collection during that time, resulting in a total of 470,798 student-reported observations. The intervention school districts received programming provided by CTC coalitions. Outcome measures were lifetime and past 30-day alcohol, tobacco, marijuana, and other drug use. Lifetime and past year participation in delinquency and current depressive symptoms were also analyzed. Analyses revealed that CTC school districts had significantly lower levels of adolescent substance use, delinquency, and depression. This effect was small to moderate, depending on the particular outcome studied. Overall effects became stronger after accounting for use of evidence-based programs; there are likely differences in implementation quality and other factors that contribute to the observed overall small effect size. Future research needs to unpack these factors.

Identifying Distinct Latent Classes of Adverse Childhood Experiences Among US Children and Their Relationship with Childhood Internalizing Disorders.

This study aimed to determine the relationship between latent classes of adverse childhood experience (ACEs) and internalizing disorders (anxiety and depression) among US children. The 2016 National Survey of Children's Health data for children aged 6-17 was used. Latent class analysis was performed to identify distinct sub-types of ACE exposures and survey-weighted logistic regression models were employed to determine whether these classes were associated with any or comorbid childhood internalizing disorders, after controlling for meaningful covariates. Four latent classes were identified: income hardship, divorce, mental health or substance abuse exposure, and high ACEs overall. Children in three of the four classes were significantly more likely to have any childhood internalizing disorder when compared to children reporting no ACEs, while children in all classes were significantly more likely to have a comorbid history of anxiety and depression. Thus, children exposed to ACEs should receive necessary mental health screenings and treatments.

Determinants of organ donation registration.

Rates of organ donor registration range from 20% to 60% throughout the United States. The purpose of this study was to examine sociogeographic differences in organ donor registration rates throughout Missouri to identify varying patterns The organ donor registration rate from each Department of Motor Vehicle office in Missouri was extracted from the National Organ Registration database, office locations were geocoded, and census tract level sociodemographic characteristics were extracted. Spatial regression analyses were conducted to identify relationships between location of DMV offices and census tract-level concentrated disadvantage. Census tract-level concentrated disadvantage (education attainment, poverty, single-headed households) had a significant negative relationship with organ donor registration rates. Yet, census tract-level African American/Black resident concentration was not significantly related to organ donor registration rates. These findings suggest that race-based interventions to recruit organ donors may no longer be necessary. Yet, identifying how characteristics of concentrated disadvantage may be more influential in determining organ donor registration. Gaining a better understanding of how individual decisions are made is integral in the context of increased life expectancy in conjunction with the complex management of chronic conditions.

Pertussis Vaccination Among Childcare Center Staff, Administrators, and Parents: Uptake, Policies, and Beliefs.

Introduction Little is known about childcare staff's and parents' uptake of and attitudes towards pertussis vaccine. Methods Questionnaires were distributed to St. Louis parents and childcare staff in fall, 2014. Parents versus staff and vaccinated versus unvaccinated individuals' beliefs regarding pertussis vaccine were compared using chi square tests. Multivariate logistic regressions were run to develop predictive models for staff's and parents' vaccine uptake. Results Overall, 351 parents and staff from 23 agencies participated (response rate = 32%). Parents were more likely than staff to have received pertussis vaccine (66.5 vs. 45.8%, X 2 = 12.5, p < .001). Predictors for staff vaccination included willingness to get vaccinated even if there was a cost (OR 6.6; CI 1.8-24.6; p < .01), awareness of vaccination recommendations (OR 5.2; CI 1.2-22.8; p < .05), and healthcare provider recommendation (OR 4.2; CI 1.2-15.1; p < .05). Parents' predictors of vaccination included perceived importance of vaccination (OR 9.9; CI 4.1-23.8; p < .001), healthcare provider recommendation (OR 4.6; CI 1.7-12.6; p < .01), believing vaccination is effective (OR 4.4; CI 1.1-18.0; p < .05), and knowing where to get vaccine (OR 3.5; CI 1.5-8.1; p < .01). Among unvaccinated staff (n = 52), 74.5% (n = 38) and 70.0% (n = 35) would receive pertussis vaccine if it were offered free of charge and onsite, respectively. Conclusions for Practice Childcare staff's and parents' pertussis vaccine uptake was higher than overall U.S. rates, though significantly lower than the Global Pertussis Initiative target. Implementing an education campaign and providing free vaccine on-site are likely to result in increased vaccine uptake.