RNA transcriptional biosignature analysis for identifying febrile infants with serious bacterial infections in the emergency department: a feasibility study.

OBJECTIVES: To develop the infrastructure and demonstrate the feasibility of conducting microarray-based RNA transcriptional profile analyses for the diagnosis of serious bacterial infections in febrile infants 60 days and younger in a multicenter pediatric emergency research network. METHODS: We designed a prospective multicenter cohort study with the aim of enrolling more than 4000 febrile infants 60 days and younger. To ensure success of conducting complex genomic studies in emergency department (ED) settings, we established an infrastructure within the Pediatric Emergency Care Applied Research Network, including 21 sites, to evaluate RNA transcriptional profiles in young febrile infants. We developed a comprehensive manual of operations and trained site investigators to obtain and process blood samples for RNA extraction and genomic analyses. We created standard operating procedures for blood sample collection, processing, storage, shipping, and analyses. We planned to prospectively identify, enroll, and collect 1 mL blood samples for genomic analyses from eligible patients to identify logistical issues with study procedures. Finally, we planned to batch blood samples and determined RNA quantity and quality at the central microarray laboratory and organized data analysis with the Pediatric Emergency Care Applied Research Network data coordinating center. Below we report on establishment of the infrastructure and the feasibility success in the first year based on the enrollment of a limited number of patients. RESULTS: We successfully established the infrastructure at 21 EDs. Over the first 5 months we enrolled 79% (74 of 94) of eligible febrile infants. We were able to obtain and ship 1 mL of blood from 74% (55 of 74) of enrolled participants, with at least 1 sample per participating ED. The 55 samples were shipped and evaluated at the microarray laboratory, and 95% (52 of 55) of blood samples were of adequate quality and contained sufficient RNA for expression analysis. CONCLUSIONS: It is possible to create a robust infrastructure to conduct genomic studies in young febrile infants in the context of a multicenter pediatric ED research setting. The sufficient quantity and high quality of RNA obtained suggests that whole blood transcriptional profile analysis for the diagnostic evaluation of young febrile infants can be successfully performed in this setting.

Management of suicidal risk in the emergency department: A clinical pathway using the computerized adaptive screen for suicidal youth.

Objective: Given the critical need for efficient and tailored suicide screening for youth presenting in the emergency department (ED), this study establishes validated screening score thresholds for the Computerized Adaptive Screen for Suicidal Youth (CASSY) and presents an example of a suicide risk classification pathway. Methods: Participants were primarily from the Study One derivation cohort of the Emergency Department Screen for Teens at Risk for Suicide (ED-STARS) enrolled in collaboration with Pediatric Emergency Care Applied Research Networks (PECARN). CASSY scores corresponded to the predicted probabilities of a suicide attempt in the next 3 months and risk thresholds were classified as minimal (<1%), low (1%-5%), moderate (5%-10%), and high (>10%). CASSY scores were compared to risk thresholds derived from clinical consensus and ED complaints and dispositions. CASSY risk thresholds were also examined as predictors of future suicide attempts in the Study Two validation cohort of ED-STARS. Results: A total of 1452 teens were enrolled with a median age of 15.2 years, 59.5% were female, 55.6% were White, 22% were Black, 22.3% were Latinx, and 42.8% received public assistance. The clinical consensus suicide risk groups were strongly associated with the CASSY-predicted risk thresholds. Suicide attempts in the Study Two cohort occurred at a frequency consistent with the CASSY-predicted thresholds. Conclusions: The CASSY can be a valuable tool in providing patient-specific risk probabilities for a suicide attempt at 3 months and tailor the threshold cutoffs based on the availability of local mental health resources. We give an example of a clinical risk pathway, which should include segmentation of the ED population by medical versus psychiatric chief complaint.

Sex Without Contraceptives in a Multicenter Study of Adolescent Emergency Department Patients.

OBJECTIVES: In the United States, rates of teenage pregnancy and sexually transmitted infections (STIs) remain exceptionally high, and racial and ethnic disparities persist. Emergency departments (EDs) care for over 19 million adolescents each year, the majority being minority and low socioeconomic status. Single-center studies demonstrate infrequent use of contraceptives among adolescent ED patients and an association between risky sex and behaviors such as alcohol and drug use; however, no multicenter ED data exist. The objectives of this study were to 1) determine the prevalence of sex without contraceptives in a large multicenter adolescent ED study and 2) assess patient demographic and risky behaviors associated with sex without contraceptives. METHODS: Participants aged 14 to 17 years (n = 3,247) in 16 pediatric EDs across the United States completed an electronic survey. Questions focused on validated measures of risky sex; use of alcohol, tobacco, marijuana, and other drugs; and depression and violence. In this secondary analysis, we constructed univariable and multivariable models to identify demographic and behavioral factors associated with sex without contraceptives (our primary outcome), separately for adolescent males and females. RESULTS: In the prior year, 17.4% (236/1,356) of males and 15.8% (299/1,891) of females had sex without contraceptives. In the multivariable model, sex without contraceptives for both genders was more likely among teens who were black, with conduct problems and participated in casual sex, binge drinking, or cannabis use. Sex without contraceptives was also more likely among Hispanic and cigarette-smoking males, as well as depressed females. CONCLUSIONS: Adolescent ED patients across the United States are participating in risky sexual behaviors that increase their likelihood of pregnancy and STI acquisition. These adolescents report a number of problem behaviors, including substance use, which are strongly correlated with unprotected sex. The ED visit may be an opportunity to identify at-risk adolescent patients, address risky behaviors, and intervene to improve adolescent health.

Implicit Review Instrument to Evaluate Quality of Care Delivered by Physicians to Children in Emergency Departments.

OBJECTIVE: To evaluate the consistency, reliability, and validity of an implicit review instrument that measures the quality of care provided to children in the emergency department (ED). DATA SOURCES/STUDY SETTING: Medical records of randomly selected children from 12 EDs in the Pediatric Emergency Care Applied Research Network (PECARN). STUDY DESIGN: Eight pediatric emergency medicine physicians applied the instrument to 620 medical records. DATA COLLECTION/EXTRACTION METHODS: We determined internal consistency using Cronbach's alpha and inter-rater reliability using the intraclass correlation coefficient (ICC). We evaluated the validity of the instrument by correlating scores with four condition-specific explicit review instruments. PRINCIPAL FINDINGS: Individual reviewers' Cronbach's alpha had a mean of 0.85 with a range of 0.76-0.97; overall Cronbach's alpha was 0.90. The ICC was 0.49 for the summary score with a range from 0.40 to 0.46. Correlations between the quality of care score and the four condition-specific explicit review scores ranged from 0.24 to 0.38. CONCLUSIONS: The quality of care instrument demonstrated good internal consistency, moderate inter-rater reliability, high inter-rater agreement, and evidence supporting validity. The instrument could be useful for systems' assessment and research in evaluating the care delivered to children in the ED.

Distinct effects of obesity and puberty on risk and age at onset of pediatric MS.

OBJECTIVE: The aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS. METHODS: Case-control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex- and age-stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex-stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity. RESULTS: Only 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls (OR = 1.60, 95% confidence interval [CI]: 1.12, 2.27, P = 0.009) and boys (OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms (P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS (P < 0.001). INTERPRETATION: Higher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity.