Congruency of Crash- and Hospital- Reported Injuries Among Child Passengers.

INTRODUCTION: Prior work has found incongruencies in injury information reported by crash and hospital records. However, no work has focused on child passengers. The objective of this study was to compare crash scene and hospital-reported injury information for crash-involved child passengers. This study also explored injury location and severity by child age and restraint type. METHODS: Utilizing linked New Jersey data from 2017 through 2019, the authors identified crash-involved child passengers <13 years old and their injuries in crash and hospital reports. Then, they characterized the congruency of injury frequency, severity, and location, as well as the frequency of injuries by child age and restraint type. Analyses were conducted from December 2023 through February 2024. RESULTS: Of 84,060 crash-involved child passengers, crash reports documented 7,858 (9%) children with at least "possible" injuries, while 2,577 (3%) had at least one injury in hospital events. Crash report and hospital data were incongruent for both body region of injury and injury severity. The proportion of children injured increased as children's ages increased and as restraint type progressed. CONCLUSIONS: Crash reports overestimated the number of injured child passengers and misrepresented injury severity and locations. Child restraint systems mitigated a child's injury risk. Importantly, injury information documented on crash reports currently informs the allocation of traffic safety resources. These results highlight the importance of improving these reports' accuracy and underscore calls to link administrative datasets for public health efforts.

Youth Suicide and Preceding Mental Health Diagnosis.

Importance: Suicide is a leading cause of death among US youths, and mental health disorders are a known factor associated with increased suicide risk. Knowledge about potential sociodemographic differences in documented mental health diagnoses may guide prevention efforts. Objective: To examine the association of documented mental health diagnosis with (1) sociodemographic and clinical characteristics, (2) precipitating circumstances, and (3) mechanism among youth suicide decedents. Design, Setting, and Participants: This retrospective, cross-sectional study of youth suicide decedents aged 10 to 24 years used data from the Centers for Disease Control and Prevention National Violent Death Reporting System from 2010 to 2021. Data analysis was conducted from January to November 2023. Exposures: Sociodemographic characteristics, clinical characteristics, precipitating circumstances, and suicide mechanism. Main Outcomes and Measures: The primary outcome was previously documented presence of a mental health diagnosis. Associations were evaluated by multivariable logistic regression. Results: Among 40 618 youth suicide decedents (23 602 aged 20 to 24 years [58.1%]; 32 167 male [79.2%]; 1190 American Indian or Alaska Native [2.9%]; 1680 Asian, Native Hawaiian, or Other Pacific Islander [4.2%]; 5118 Black [12.7%]; 5334 Hispanic [13.2%]; 35 034 non-Hispanic; 30 756 White [76.1%]), 16 426 (40.4%) had a documented mental health diagnosis and 19 027 (46.8%) died by firearms. The adjusted odds of having a mental health diagnosis were lower among youths who were American Indian or Alaska Native (adjusted odds ratio [aOR], 0.45; 95% CI, 0.39-0.51); Asian, Native Hawaiian, or Other Pacific Islander (aOR, 0.58; 95% CI, 0.52-0.64); and Black (aOR, 0.62; 95% CI, 0.58-0.66) compared with White youths; lower among Hispanic youths (aOR, 0.76; 95% CI, 0.72-0.82) compared with non-Hispanic youths; lower among youths aged 10 to 14 years (aOR, 0.70; 95% CI, 0.65-0.76) compared with youths aged 20 to 24 years; and higher for females (aOR, 1.64; 95% CI, 1.56-1.73) than males. A mental health diagnosis was documented for 6308 of 19 027 youths who died by firearms (33.2%); 1691 of 2743 youths who died by poisonings (61.6%); 7017 of 15 331 youths who died by hanging, strangulation, or suffocation (45.8%); and 1407 of 3181 youths who died by other mechanisms (44.2%). Compared with firearm suicides, the adjusted odds of having a documented mental health diagnosis were higher for suicides by poisoning (aOR, 1.70; 95% CI, 1.62-1.78); hanging, strangulation, and suffocation (aOR, 2.78; 95% CI, 2.55-3.03); and other mechanisms (aOR, 1.59; 95% CI, 1.47-1.72). Conclusions and Relevance: In this cross-sectional study, 3 of 5 youth suicide decedents did not have a documented preceding mental health diagnosis; the odds of having a mental health diagnosis were lower among racially and ethnically minoritized youths than White youths and among firearm suicides compared with other mechanisms. These findings underscore the need for equitable identification of mental health needs and universal lethal means counseling as strategies to prevent youth suicide.

Obesity is associated with increased pediatric dengue virus infection and disease: A 9-year cohort study in Managua, Nicaragua.

BACKGROUND: Obesity is on the rise globally in adults and children, including in tropical areas where diseases such as dengue have a substantial burden, particularly in children. Obesity impacts the risk of severe dengue disease; however, the impact on dengue virus (DENV) infection and dengue cases remains an open question. METHODS: We used 9 years of data from 5,940 children in the Pediatric Dengue Cohort Study in Nicaragua to examine whether pediatric obesity is associated with increased susceptibility to DENV infection and symptomatic presentation. Analysis was performed using Generalized Estimating Equations adjusted for age, sex, and pre-infection DENV antibody titers. RESULTS: From 2011 to 2019, children contributed 26,273 person-years of observation, and we observed an increase in the prevalence of overweight (from 12% to 17%) and obesity (from 7% to 13%). There were 1,682 DENV infections and 476 dengue cases in the study population. Compared to participants with normal weight, participants with obesity had higher odds of DENV infection (Adjusted Odds Ratio [aOR] 1.21, 95% confidence interval [CI] 1.03-1.42) and higher odds of dengue disease given infection (aOR 1.59, 95% CI 1.15-2.19). Children with obesity infected with DENV showed increased odds of presenting fever (aOR 1.46, 95% CI 1.05-2.02), headache (aOR 1.51, 95% CI 1.07-2.14), and rash (aOR 2.26, 95% CI 1.49-3.44) when compared with children with normal weight. CONCLUSIONS: Our results indicate that obesity is associated with increased susceptibility to DENV infection and dengue cases in children, independently of age, sex, and pre-infection DENV antibody titers.

RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events.

Background: Hematopoietic transcription factor RUNX1 is expressed from proximal P2 and distal P1 promoter to yield isoforms RUNX1 B and C, respectively. The roles of these isoforms in RUNX1 autoregulation and downstream-gene regulation in megakaryocytes and platelets are unknown. Objectives: To understand the regulation of RUNX1 and its target genes by RUNX1 isoforms. Methods: We performed studies on RUNX1 isoforms in megakaryocytic HEL cells and HeLa cells (lack endogenous RUNX1), in platelets from 85 healthy volunteers administered aspirin or ticagrelor, and on the association of RUNX1 target genes with acute events in 587 patients with cardiovascular disease (CVD). Results: In chromatin immunoprecipitation and luciferase promoter assays, RUNX1 isoforms B and C bound and regulated P1 and P2 promoters. In HeLa cells RUNX1B decreased and RUNX1C increased P1 and P2 activities, respectively. In HEL cells, RUNX1B overexpression decreased RUNX1C and RUNX1A expression; RUNX1C increased RUNX1B and RUNX1A. RUNX1B and RUNX1C regulated target genes (MYL9, F13A1, PCTP, PDE5A and others) differentially in HEL cells. In platelets RUNX1B transcripts (by RNAseq) correlated negatively with RUNX1C and RUNX1A; RUNX1C correlated positively with RUNX1A. RUNX1B correlated positively with F13A1, PCTP, PDE5A, RAB1B, and others, and negatively with MYL9. In our previous studies, RUNX1C transcripts in whole blood were protective against acute events in CVD patients. We found that higher expression of RUNX1 targets F13A1 and RAB31 associated with acute events. Conclusions: RUNX1 isoforms B and C autoregulate RUNX1 and regulate downstream genes in a differential manner and this associates with acute events in CVD.

Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression.

Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.

Preparing to "Live a Life of Possibilities": Experiences of Healthcare Providers Readying Autistic Adolescents and Their Families for Independent Driving.

Autistic adolescents and their families may experience barriers to transportation, including independent driving, which is critical to supporting quality of life and engagement in social, educational, and employment opportunities. Healthcare providers may feel unprepared to provide guidance to autistic adolescents, although they are among the professionals families turn to for guidance. This study describes providers' experiences supporting autistic adolescents and families in the decision to pursue licensure and identifies barriers experienced in providing support. We conducted interviews with 15 healthcare providers focused on how they support autistic adolescents and their families in navigating topics related to independence, driving, and transportation. Key themes identified included: importance of understanding adolescents' perspectives and motivations, approaches to readying caregivers for children to pursue driving, and role of providers in fostering agreement between adolescents and caregivers. Results reflect healthcare providers as intermediaries between autistic adolescents and caregivers making the decision to pursue licensure and bring families to consensus. Our findings emphasize the importance of healthcare providers, in collaboration with community-based providers, in supporting autistic adolescents and their families considering licensure. Improving conversations between providers and families provides opportunity to better support quality of life among autistic adolescents and their caregivers navigating the transition to independence.

Obesity is associated with increased pediatric dengue virus infection and disease: A 9-year cohort study in Managua, Nicaragua.

Background: Obesity is on the rise globally in adults and children, including in tropical areas where diseases such as dengue have a substantial burden, particularly in children. Obesity impacts the risk of severe dengue disease; however, the impact on dengue virus (DENV) infection and dengue cases remains an open question. Methods: We used 9 years of data from 5,940 children in the Pediatric Dengue Cohort Study in Nicaragua to examine whether pediatric obesity is associated with increased susceptibility to DENV infection and symptomatic presentation. Analysis was performed using Generalized Estimating Equations adjusted for age, sex, and pre-infection DENV antibody titers. Results: From 2011 to 2019, children contributed 26,273 person-years of observation, and we observed an increase in the prevalence of overweight (from 12% to 17%) and obesity (from 7% to 13%). There were 1,682 DENV infections and 476 dengue cases in the study population. Compared to participants with normal weight, participants with obesity had higher odds of DENV infection (Adjusted Odds Ratio [aOR] 1.21, 95% confidence interval [CI] 1.03-1.42) and higher odds of dengue disease given infection (aOR 1.59, 95% CI 1.15-2.19). Children with obesity infected with DENV showed increased odds of presenting fever (aOR 1.46, 95% CI 1.05-2.02), headache (aOR 1.51, 95% CI 1.07-2.14), and rash (aOR 2.26, 95% CI 1.49-3.44) when compared with children with normal weight. Conclusions: Our results indicate that obesity is associated with increased susceptibility to DENV infection and dengue cases in children, independently of age, sex, and pre-infection DENV antibody titers.

Caregivers' Perspectives on Use of and Need for Driving Resources for Their Autistic Adolescent.

Introduction: Autistic individuals who independently travel-or commute without companionship or supervision-report feeling more connected to social, education, and employment opportunities. Despite the potential for independent transportation to improve quality of life, little is known about what transportation-related resources, specifically driving focused ones, exist for autistic individuals or how they and their families find and use them. The objectives of this study were to characterize: (1) where and how families in the United States find driving-related resources for their autistic adolescents; (2) families' perceived availability and utility of identified resources; and (3) resources families believe should be developed. Methods: We conducted semi-structured interviews with 33 caregivers of autistic adolescents aged 16-24 years without an intellectual disability. We used a directed-content approach to develop and implement codes; three trained coders analyzed all transcripts (inter-rater reliability ≥0.8 for all codes). Members of the research team reviewed coded data and created code summaries, which were then developed and discussed by the larger research team to determine final consensus. Results: Caregivers described a few existing resources that were helpful in guiding driving-related decisions. In addition, caregivers voiced that there were limited resources tailored to the unique needs that arise while teaching or learning how to drive, particularly ones that support their own and their adolescent's mental health. The limited resources and services identified as helpful-specifically support groups/perspectives of other families and specialized driving instructors-are seemingly difficult to find, costly, and/or perceived as having geographic- and time-related barriers. Conclusion: There is a critical need and opportunity for stakeholders of the autism community to both expand access to existing and develop novel driving-related resources for families with autistic adolescents, with a particular focus of supporting caregiver and adolescent mental health.

Why is this an important issue?: Many autistic teens and young adults rely on caregivers, siblings, family, and friends to give them rides to the places they need to go. Research has found that resources and services created specifically for autistic people can help them decide whether driving is right for them, and if so, then learn how to drive. However, little is known about if, and if so how, families find or use these resources and services. What was the purpose of this study?: This study had three goals: (1) learn what driving resources and services autistic teens and young adults (and their families) use, (2) learn how they find these resources and services, and (3) learn what other things they think would help them make decisions about driving and learn how to drive. What did the researchers do?: The researchers asked 33 caregivers of autistic teens and young adults without an intellectual disability (ID) (teens and young adults were 16­24 years old) questions about their experiences finding and using driving resources and services. These conversations were recorded and later typed out word for word. What were the results of the study?: Caregivers said that they spend a lot of time looking for driving resources and services for their autistic teen or young adult. Many resources and services were not easy to use or helpful. Caregivers said that behind-the-wheel driving instructors with specific training teaching autistic individuals were the most helpful and/or wanted resource. However, caregivers also said that these instructors and their services were hard to find, cost a lot of money, and require families to spend a lot of time training with them to get results. In the future, caregivers said that making it easier to find and get driving resources and services (e.g., making them less expensive) was necessary. Caregivers also had strong interest in their family participating in support groups related to driving. What do these findings add to what was already known?: Previous research has shown that training, resources, and services designed specifically for autistic people help prepare autistic teens and young adults to drive. Before our study, it was unclear if, and if so how, families actually use these resources and services in the real world, or outside of academic research. Families in our study said that it is hard to find or get access to driving resources and services, especially those created specifically for autistic populations. This difficulty is one reason why families think it is stressful and hard for autistic teens and young adults to learn how to drive. What are the potential weaknesses in the study?: We only asked caregivers who lived in the Northeast part of the United States questions, so our findings may not be true for all families. Also, this study only asked questions to caregivers of autistic teens and young adults who did not have an ID. How will these findings help autistic adults now or in the future?: Our findings can help autistic teens and young adults by showing what resources and services families use and want to use while they are learning how to drive or making decisions about if driving is right for them.

Early reduction in cardiorespiratory fitness and diastolic reserve following radiation therapy for lung cancer.

BACKGROUND: Contemporary radiotherapy for the treatment of lung cancer is effective in targeting tumor tissue while limiting heart exposure, yet cardiac toxicity still occurs, often becoming clinically apparent years later. Cardiorespiratory fitness (CRF) is an independent predictor of cardiovascular, cancer-related, and overall mortality and may serve as a sensitive measure of subclinical cardiac toxicity following anti-cancer treatments. Prior work has demonstrated a significant relationship between reduced CRF and impaired left-ventricular (LV) diastolic reserve in cancer survivors following thoracic radiotherapy. The purpose of this study was to assess early longitudinal changes in CRF and cardiac function in patients with lung cancer following radiotherapy. METHODS: Ten patients (69 [61-76] years, 70% female) with lung cancer without known cardiovascular disease scheduled to receive radiotherapy involving a clinically-relevant heart dose (≥ 5 Gy to > 10% of heart volume) were evaluated prior to and following treatment. Changes in CRF (peak oxygen consumption [VO2peak], oxygen uptake efficiency slope [OUES]), cardiac function (LV ejection fraction [LVEF], rest and exercise diastolic function [diastolic functional reserve index (DFRI)]), cardiac biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity C-reactive protein [hsCRP]), and health-related quality of life (HRQOL; Functional Assessment of Cancer Therapy-General-7 [FACT-G7]) were measured. RESULTS: The VO2peak was reduced at baseline (1.245 [0.882-1.605] L·min- 1; 70 [62-86] %-predicted) and significantly declined (1.095 [0.810-1.448] L·min- 1, P = 0.047; 62 [56-76] %-predicted, P = 0.005) at 6.0 [3.0-6.0] months post-radiotherapy. Similarly, a significant decline in the OUES was observed (1.63 [1.27-1.88] to 1.57 [1.12-1.75], P = 0.032). Systolic cardiac function was normal at baseline and did not change following radiotherapy (LVEF; 62 [56-65]% to 66 [57-68]%, P = 0.475). The DFRI significantly declined following radiotherapy (34.9 [22.7-41.6] vs. 12.8 [3.1-35.9]). The hsCRP increased significantly from 4.4 [1.4-5.8] to 6.1 [3.7-20.7] g/L, P = 0.047 with a trend towards higher levels of NT-proBNP (65 [49-125] to 121 [88-191] pg/mL, P = 0.110). Health-related quality of life significantly decreased (FACT-G7; 21.5 [18.8-25] to 15.5 [11.5-20]; P = 0.021) post-radiotherapy. CONCLUSIONS: Patients with lung cancer receiving radiotherapy with a clinically-significant heart dose experience reductions in CRF (VO2peak, OUES) as early as six months following treatment with concurrent reductions in diastolic reserve (DFRI), HRQOL, and increases in cardiac biomarkers (NT-proBNP, hsCRP).

Platelet RNA Biomarker of Ticagrelor-Responsive Genes Is Associated With Platelet Function and Cardiovascular Events.

BACKGROUND: Identifying patients with the optimal risk:benefit for ticagrelor is challenging. The aim was to identify ticagrelor-responsive platelet transcripts as biomarkers of platelet function and cardiovascular risk. METHODS: Healthy volunteers (n=58, discovery; n=49, validation) were exposed to 4 weeks of ticagrelor with platelet RNA data, platelet function, and self-reported bleeding measured pre-/post-ticagrelor. RNA sequencing was used to discover platelet genes affected by ticagrelor, and a subset of the most informative was summarized into a composite score and tested for validation. This score was further analyzed (1) in CD34+ megakaryocytes exposed to an P2Y12 inhibitor in vitro, (2) with baseline platelet function in healthy controls, (3) in peripheral artery disease patients (n=139) versus patient controls (n=30) without atherosclerosis, and (4) in patients with peripheral artery disease for correlation with atherosclerosis severity and risk of incident major adverse cardiovascular and limb events. RESULTS: Ticagrelor exposure differentially expressed 3409 platelet transcripts. Of these, 111 were prioritized to calculate a Ticagrelor Exposure Signature score, which ticagrelor reproducibly increased in discovery and validation cohorts. Ticagrelor's effects on platelets transcripts positively correlated with effects of P2Y12 inhibition in primary megakaryocytes. In healthy controls, higher baseline scores correlated with lower baseline platelet function and with minor bleeding while receiving ticagrelor. In patients, lower scores independently associated with both the presence and extent of atherosclerosis and incident ischemic events. CONCLUSIONS: Ticagrelor-responsive platelet transcripts are a biomarker for platelet function and cardiovascular risk and may have clinical utility for selecting patients with optimal risk:benefit for ticagrelor use.

Simultaneous exercise stress cardiac magnetic resonance and cardiopulmonary exercise testing to elucidate the Fick components of aerobic exercise capacity: a feasibility and reproducibility study and pilot study in hematologic cancer survivors.

BACKGROUND: Patients treated for hematologic malignancy often experience reduced exercise capacity and increased fatigue; however whether this reduction is related to cardiac dysfunction or impairment of skeletal muscle oxygen extraction during activity is unknown. Cardiopulmonary exercise testing (CPET) coupled with stress cardiac magnetic resonance (ExeCMR), may provide a noninvasive method to identify the abnormalities of cardiac function or skeletal muscle oxygen extraction. This study was performed to determine the feasibility and reproducibility of a ExeCMR + CPET technique to measure the Fick components of peak oxygen consumption (VO2) and pilot its discriminatory potential in hematologic cancer patients experiencing fatigue. METHODS: We studied 16 individuals undergoing ExeCMR to determine exercise cardiac reserve with simultaneous measures of VO2. The arteriovenous oxygen content difference (a-vO2diff) was calculated as the quotient of VO2/cardiac index (CI). Repeatability in measurements of peak VO2, CI, and a-vO2diff was assessed in seven healthy controls. Finally, we measured the Fick determinants of peak VO2 in hematologic cancer survivors with fatigue (n = 6) and compared them to age/gender-matched healthy controls (n = 6). RESULTS: Study procedures were successfully completed without any adverse events in all subjects (N = 16, 100%). The protocol demonstrated good-excellent test-retest reproducibility for peak VO2 (intraclass correlation coefficient [ICC] = 0.992 [95%CI:0.955-0.999]; P < 0.001), peak CI (ICC = 0.970 [95%CI:0.838-0.995]; P < 0.001), and a-vO2diff (ICC = 0.953 [95%CI:0.744-0.992]; P < 0.001). Hematologic cancer survivors with fatigue demonstrated a significantly lower peak VO2 (17.1 [13.5-23.5] vs. 26.0 [19.7-29.5] mL·kg-1·min-1, P = 0.026) and lower peak CI (5.0 [4.7-6.3] vs. 7.4 [7.0-8.8] L·min-1/m2, P = 0.004) without a significant difference in a-vO2diff (14.4 [11.8-16.9] vs. 13.6 [10.9-15.4] mLO2/dL, P = 0.589). CONCLUSIONS: Noninvasive measurement of peak VO2 Fick determinants is feasible and reliable with an ExeCMR + CPET protocol in those treated for a hematologic malignancy and may offer insight into the mechanisms of exercise intolerance in those experiencing fatigue.

Variation in drivers' seat belt use by indicators of community-level vulnerability.

INTRODUCTION: Examining crash reports with linked community-level indicators may optimize efforts aimed at improving traffic safety behaviors, like seat belt use. To examine this, quasi-induced exposure (QIE) methods and linked data were used to (a) estimate trip-level seat belt non-use of New Jersey (NJ) drivers and (b) determine the degree to which seat belt non-use is associated with community-level indicators of vulnerability. METHOD: Driver-specific characteristics were identified from crash reports (age, sex, number of passengers, vehicle type) and licensing data (license status at the time of the crash). Geocoded residential addresses were leveraged within the NJ Safety and Health Outcomes warehouse to create quintiles of community-level vulnerability. QIE methods were applied to estimate trip-level prevalence of seat belt non-use in non-responsible, crash-involved drivers between 2010-2017 (n = 986,837). Generalized linear mixed models were then conducted to calculate adjusted prevalence ratios and 95 % confidence intervals for being unbelted for driver-specific variables and community-level indicators of vulnerability. RESULTS: Drivers were unbelted during 1.2 % of trips. Males, those with suspended licenses, and those without passengers had higher rates of being unbelted than their counterparts. An increase was observed in traveling unbelted with increasing quintiles of vulnerability, such that drivers in the most vulnerable communities were 121 % more likely to be unbelted than those in the least vulnerable communities. CONCLUSIONS: Prevalence of driver seat belt non-use may be lower than previously estimated. Additionally, communities with the highest amount of the population living with three or more indicators of vulnerability have higher rates of seat belt non-use; this may be a particularly useful metric to inform future translational efforts improving seat belt use. PRACTICAL APPLICATIONS: As evidenced by the findings that risk of being unbelted increased as drivers' community vulnerability increased, novel communication efforts tailored to drivers from vulnerable neighborhoods may optimize efforts.

Lung Ultrasound Protocol and Quality Control of Image Interpretation Using an Adjudication Panel in the Household Air Pollution Intervention Network (HAPIN) Trial.

OBJECTIVE: Lung ultrasound (LUS) is an alternative to chest radiography to confirm a diagnosis of pneumonia. For research and disease surveillance, methods to use LUS to diagnose pneumonia are needed. METHODS: In the Household Air Pollution Intervention Network (HAPIN) trial, LUS was used to confirm a clinical diagnosis of severe pneumonia in infants. We developed a standardized definition of pneumonia, protocols for recruitment and training of sonographers, along with LUS image acquisition and interpretation. We use a blinded panel approach to interpretation with LUS cine-loops randomized to non-scanning sonographers with expert review. DISCUSSION: We obtained 357 lung ultrasound scans: 159, 8 and 190 scans were collected in Guatemala, Peru and Rwanda, respectively. The diagnosis of primary endpoint pneumonia (PEP) required an expert tie breaker in 181 scans (39%). PEP was diagnosed in 141 scans (40%), not diagnosed in 213 (60%), with 3 scans (<1%) deemed uninterpretable. Agreement among the two blinded sonographers and the expert reader in Guatemala, Peru and Rwanda was 65%, 62% and 67%, with a prevalence-and-bias-corrected kappa of 0.30, 0.24 and 0.33, respectively. CONCLUSION: Use of standardized imaging protocols, training and an adjudication panel resulted in high confidence for the diagnosis of pneumonia using LUS.

Transcriptional responses define dysregulated immune activation in Hepatitis C (HCV)-naïve recipients of HCV-infected donor kidneys.

Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to dysregulated immunologic activation secondary to active inflammation from acute viremia at the time of transplantation. This includes increased rates of cytomegalovirus (CMV) DNAemia and allograft rejection. In this study, we evaluate transcriptional responses in circulating leukocytes to define the character, timing, and resolution of this immune dysregulation and assess for biomarkers of adverse outcomes in transplant patients. We enrolled 67 renal transplant recipients (30 controls, 37 HCV recipients) and performed RNA sequencing on serial samples from one, 3-, and 6-months post-transplant. CMV DNAemia and allograft rejection outcomes were measured. Least absolute shrinkage and selection operator was utilized to develop gene expression classifiers predictive of clinical outcomes. Acute HCV incited a marked transcriptomic response in circulating leukocytes of renal transplant recipients in the acute post-transplant setting, despite the presence of immunosuppression, with 109 genes significantly differentially expressed compared to controls. These HCV infection-associated genes were reflective of antiviral immune pathways and generally resolved by the 3-month timepoint after sustained viral response (SVR) for HCV. Differential gene expression was also noted from patients who developed CMV DNAemia or allograft rejection compared to those who did not, although transcriptomic classifiers could not accurately predict these outcomes, likely due to sample size and variable time-to-event. Acute HCV infection incites evidence of immune activation and canonical antiviral responses in the human host even in the presence of systemic immunosuppression. After treatment of HCV with antiviral therapy and subsequent aviremia, this immune activation resolves. Changes in gene expression patterns in circulating leukocytes are associated with some clinical outcomes, although larger studies are needed to develop accurate predictive classifiers of these events.

An antiplatelet response gene expression signature is associated with bleeding.

AIMS: Gene expression biosignatures may hold promise to individualize antiplatelet therapy in conjunction with current guidelines and risk scores. The Aspirin Response Signature (ARS) score is comprised of a weighted sum of correlated, pro-thrombotic gene transcripts measured in whole blood. In prior work where volunteers were exposed to aspirin 325 mg daily, higher ARS score was associated with lower platelet function; separately, in a clinical cohort of patients, higher ARS scores were associated with increased risk of adverse cardiovascular events. To better understand this apparent paradox, we measured ARS gene expression and score in volunteers to determine aspirin dose-response and ticagrelor relationships with ARS score and separately in patients to assess whether ARS is associated with incident bleeding. METHODS AND RESULTS: Blood samples were collected from volunteers (N = 188) who were exposed to 4 weeks of daily aspirin 81 mg, daily aspirin 325 mg, and/or twice-daily ticagrelor 90 mg. ARS scores were calculated from whole blood RNA qPCR, and platelet function and protein expression were assessed in platelet-rich plasma. In mixed linear regression models, aspirin 81 mg exposure was not associated with changes in ARS gene expression or score. Aspirin 325 mg exposure resulted in a 6.0% increase in ARS gene expression (P = 7.5 × 10-9 vs. baseline, P = 2.1 × 10-4 vs. aspirin 81 mg) and an increase in expression of platelet proteins corresponding to ARS genes. Ticagrelor exposure resulted in a 30.7% increase in ARS gene expression (P < 1 × 10-10 vs. baseline and each aspirin dose) and ARS score (P = 7.0 × 10-7 vs. baseline, P = 3.6 × 10-6 and 5.59 × 10-4 vs. aspirin 81 and 325 mg, respectively). Increases in ARS gene expression or score were associated with the magnitude of platelet inhibition across agents. To assess the association between ARS scores and incident bleeding, ARS scores were calculated in patients undergoing cardiac catheterization (N = 1421), of whom 25.4% experienced bleeding events over a median 6.2 years of follow-up. In a Cox model adjusting for demographics and baseline antithrombotic medication use, patients with ARS scores above the median had a higher risk of incident bleeding [hazard ratio 1.26 (95% CI 1.01-1.56), P = 0.038]. CONCLUSIONS: The ARS is an Antiplatelet Response Signature that increases in response to greater platelet inhibition due to antiplatelet therapy and may represent a homeostatic mechanism to prevent bleeding. ARS scores could inform future strategies to prevent bleeding while maintaining antiplatelet therapy's benefit of ischaemic cardiovascular event protection.

Brief Report: Healthcare Providers' Discussions Regarding Transportation and Driving with Autistic and Non-autistic Patients.

OBJECTIVE: To characterize healthcare and behavioral service providers' transportation-related discussions with their autistic and non-autistic patients. METHOD: 78 providers completed a cross-sectional survey assessing their transportation discussions with patients. We used Mann-Whitney U tests and chi-square tests to compare differences in provider reports by patient diagnosis. RESULTS: Compared with one in two providers who reported they discuss transportation with non-autistic patients, only one in five have these conversations with their autistic patients. Few (8%) providers felt prepared to assess driving readiness in autistic patients, yet only a quarter refer patients elsewhere. CONCLUSION: There is a critical need to develop resources for use in medical settings to effectively support autistic adolescents' independence and mobility as they transition into adulthood.

Implementation-effectiveness trial of systematic family health history based risk assessment and impact on clinical disease prevention and surveillance activities.

BACKGROUND: Systematically assessing disease risk can improve population health by identifying those eligible for enhanced prevention/screening strategies. This study aims to determine the clinical impact of a systematic risk assessment in diverse primary care populations. METHODS: Hybrid implementation-effectiveness trial of a family health history-based health risk assessment (HRA) tied to risk-based guideline recommendations enrolling from 2014-2017 with 12 months of post-intervention survey data and 24 months of electronic medical record (EMR) data capture. SETTING: 19 primary care clinics at four geographically and culturally diverse U.S. healthcare systems. PARTICIPANTS: any English or Spanish-speaking adult with an upcoming appointment at an enrolling clinic. METHODS: A personal and family health history based HRA with integrated guideline-based clinical decision support (CDS) was completed by each participant prior to their appointment. Risk reports were provided to patients and providers to discuss at their clinical encounter. OUTCOMES: provider and patient discussion and provider uptake (i.e. ordering) and patient uptake (i.e. recommendation completion) of CDS recommendations. MEASURES: patient and provider surveys and EMR data. RESULTS: One thousand eight hundred twenty nine participants (mean age 56.2 [SD13.9], 69.6% female) completed the HRA and had EMR data available for analysis. 762 (41.6%) received a recommendation (29.7% for genetic counseling (GC); 15.2% for enhanced breast/colon cancer screening). Those with recommendations frequently discussed disease risk with their provider (8.7%-38.2% varied by recommendation, p-values ≤ 0.004). In the GC subgroup, provider discussions increased referrals to counseling (44.4% with vs. 5.9% without, P < 0.001). Recommendation uptake was highest for colon cancer screening (provider = 67.9%; patient = 86.8%) and lowest for breast cancer chemoprevention (0%). CONCLUSIONS: Systematic health risk assessment revealed that almost half the population were at increased disease risk based on guidelines. Risk identification resulted in shared discussions between participants and providers but variable clinical action uptake depending upon the recommendation. Understanding the barriers and facilitators to uptake by both patients and providers will be essential for optimizing HRA tools and achieving their promise of improving population health. TRIAL REGISTRATION: Clinicaltrials.gov number NCT01956773 , registered 10/8/2013.

Restraint use characteristics among crash-involved child passengers: identifying opportunities to enhance optimal restraint use.

OBJECTIVE: Our objective was to describe child passenger restraint use in police reported crashes by key child and driver characteristics. METHODS: We used data from 2017-2019 police reported crashes in New Jersey to identify child passengers who: (1) were less than 13 years of age, (2) were in an identified seating location in the first, second, or third vehicle row, and (3) had a known restraint status at the time of the crash. We described prevalence of child restraint use by key child and driver characteristics (child: age, sex, seating position, and crash-reported injury status; driver: age, sex, restraint use, evidenced alcohol use, and crash fault). We included 108,780 crash-involved child passengers in our analytic sample. RESULTS: A small proportion of child passengers were unrestrained at the time of the crash. Most child passengers <2 years were restrained in a rear-facing restraint (59.7%). However, a sizeable proportion were either forward-facing (26.7%) or belted (11.3%). Use of booster seats among passengers age 5 to 8 years was limited. We observed few fatalities, with most children noted to have no apparent injury (89.8%). Among children with serious, minor, and possible injuries, the greatest proportion of injured children were restrained by the vehicle belt. Regarding driver characteristics, slightly more than half of child passengers riding in vehicles driven by drivers aged 21-34 years were restrained in either rear- or forward-facing restraints (53.0%), whereas the majority of children riding with younger (<21 years) or older (>34 years) drivers were restrained with the vehicle belt. Among unrestrained drivers, drivers with evidence of alcohol use, and drivers at fault for the crash, a larger proportion of children were unrestrained compared to drivers who were restrained, had no evidence of alcohol use, and were not at fault. CONCLUSIONS: While most child passengers were restrained at the time a crash, optimal age-based restraint use was inconsistent, particularly for the youngest child passengers. A sizeable proportion of drivers in this study failed to adhere to best practice recommendations for child restraint use and New Jersey child passenger restraint laws. This was particularly true for drivers who engaged in unsafe driving behaviors, for whom a larger proportion child passengers were unrestrained at the time of the crash. Across all injury categories, the greatest proportion of injured children were restrained by the vehicle belt rather than a child restraint system, suggesting a continued need to understand specific patterns of injuries to inform possible mitigation efforts. Future work to identify intervention opportunities for optimal child restraint practices for drivers is essential to enhancing child passenger safety.

Assault-Related Concussion in a Pediatric Population.

OBJECTIVES: The aim of this study was to compare demographic characteristics, medical care, and outcomes among patients with assault-related concussion (ARC) versus sports and recreation-related concussion (SRC). METHODS: We conducted a retrospective chart review of 124 patients (62 ARC, 62 SRC) aged 8 to 17 years presenting to the care network of a large tertiary care pediatric hospital between July 1, 2012, and June 30, 2014 with a concussion diagnosis at time of presentation. We abstracted patient demographics, initial medical care visit characteristics, and outcome data, and compared proportions using χ2 testing and Fisher exact test and medians using Wilcoxon rank sum test. RESULTS: Patients with ARC were more likely to be Black, publicly insured, and present first for care to the emergency department. Significantly fewer patients with ARC received visio-vestibular testing at initial visit (27% vs 74%, P < 0.001). During recovery, the total number of reported physical, cognitive, emotional, and sleep symptoms did not differ between groups; however, more than twice as many patients with ARC reported decline in grades postinjury compared with patients with SRC (47% vs 20%, P = 0.012). There were trends toward prolonged symptom recovery and time to physician clearance for full return to activities among patients with ARC compared with SRC. CONCLUSIONS: This study highlights potential disparities in the initial evaluation and outcomes of pediatric concussion patients based on mechanism of injury. Patients with ARC were less likely to receive a concussion-specific diagnostic evaluation and reported a greater impact on educational outcomes, suggesting differences in concussion diagnosis and management among assault-injured patients. Further examination in larger populations with prospective studies is needed to address potential inequities in concussion care and outcomes among patients with ARC.