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Importance Young febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns (“RNA biosignatures”) in response to infections may provide an alternative diagnostic approach. Objective To assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections. Design, Setting, and Participants Prospective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature >38 ° C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type. Exposure RNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections. Main Outcomes and Measures Bacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores. Results Of 1883 febrile infants (median age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections—including 32 with bacteremia and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87% (95% CI, 73%-95%) sensitivity and 89% (95% CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections in the test set with 94% (95% CI, 70%-100%) sensitivity and 95% (95% CI, 88%-98%) specificity. The incremental C statistic for the RNA biosignatures over the YOS score was 0.37 (95% CI, 0.30-0.43). Conclusions and Relevance In this preliminary study, RNA biosignatures were defined to distinguish febrile infants aged 60 days or younger with and without bacterial infections. Further research with larger populations is needed to refine and validate the estimates of test accuracy and to assess the clinical utility of RNA biosignatures in practice.

Objective To determine if patient race/ethnicity is independently associated with cranial computed tomography (CT) use among children with minor blunt head trauma. Design Secondary analysis of a prospective cohort study. Setting Pediatric research network of 25 North American emergency departments. Patients In total, 42 412 children younger than 18 years were seen within 24 hours of minor blunt head trauma. Of these, 39 717 were of documented white non-Hispanic, black non-Hispanic, or Hispanic race/ethnicity. Using a previously validated clinical prediction rule, we classified each child's risk for clinically important traumatic brain injury to describe injury severity. Because no meaningful differences in cranial CT rates were observed between children of black non-Hispanic race/ethnicity vs Hispanic race/ethnicity, we combined these 2 groups. Main Outcome Measure Cranial CT use in the emergency department, stratified by race/ethnicity. Results In total, 13 793 children (34.7%) underwent cranial CT. The odds of undergoing cranial CT among children with minor blunt head trauma who were at higher risk for clinically important traumatic brain injury did not differ by race/ethnicity. In adjusted analyses, children of black non-Hispanic or Hispanic race/ethnicity had lower odds of undergoing cranial CT among those who were at intermediate risk (odds ratio, 0.84; 95% CI, 0.76-0.94) or lowest risk (odds ratio, 0.73; 95% CI, 0.66-0.81) for clinically important traumatic brain injury. Regardless of risk for clinically important traumatic brain injury, parental anxiety and request was commonly cited by physicians as an important influence for ordering cranial CT in children of white non-Hispanic race/ethnicity. Conclusions Disparities may arise from the overuse of cranial CT among patients of nonminority races/ethnicities. Further studies should focus on explaining how medically irrelevant factors, such as patient race/ethnicity, can affect physician decision making, resulting in exposure of children to unnecessary health care risks.

Objective To determine the prevalence of clinically important traumatic brain injuries (TBIs) with severe injury mechanisms in children with minor blunt head trauma but with no other risk factors from the Pediatric Emergency Care Applied Research Network (PECARN) TBI prediction rules (defined as isolated severe injury mechanisms). Design Secondary analysis of a large prospective observational cohort study. Setting Twenty-five emergency departments participating in the PECARN. Patients Children with minor blunt head trauma and Glasgow Coma Scale scores of at least 14. Intervention Treating clinicians completed a structured data form that included injury mechanism (severity categories defined a priori). Main Outcome Measures Clinically important TBIs were defined as intracranial injuries resulting in death, neurosurgical intervention, intubation for more than 24 hours, or hospital admission for at least 2 nights. We investigated the rate of clinically important TBIs in children with either severe injury mechanisms or isolated severe injury mechanisms. Results Of the 42 412 patients enrolled in the overall study, 42 099 (99%) had injury mechanisms recorded, and their data were included for analysis. Of all study patients, 6263 (15%) had severe injury mechanisms, and 3630 (9%) had isolated severe injury mechanisms. Overall, 367 children had clinically important TBIs (0.9%; 95% CI, 0.8%-1.0%). Of the 1330 children younger than 2 years with isolated severe injury mechanisms, 4 (0.3%; 95% CI, 0.1%-0.8%) had clinically important TBIs, as did 12 of the 2300 children 2 years or older (0.5%; 95% CI, 0.3%-0.9%). Conclusion Children with isolated severe injury mechanisms are at low risk of clinically important TBI, and many do not require emergent neuroimaging.