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Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger

Mahajan, Prashant; Kuppermann, Nathan; Mejias, Asuncion; Suarez, Nicolas; Chaussabel, Damien; Casper, T Charles; Smith, Bennett; Alpern, Elizabeth R; Anders, Jennifer; Atabaki, Shireen M; Bennett, Jonathan E; Blumberg, Stephen; Bonsu, Bema; Borgialli, Dominic; Brayer, Anne; Browne, Lorin; Cohen, Daniel M; Crain, Ellen F; Cruz, Andrea T; Dayan, Peter S; Gattu, Rajender; Greenberg, Richard; Hoyle, John D Jr; Jaffe, David M; Levine, Deborah A; Lillis, Kathleen; Linakis, James G; Muenzer, Jared; Nigrovic, Lise E; Powell, Elizabeth C; Rogers, Alexander J; Roosevelt, Genie; Ruddy, Richard M; Saunders, Mary; Tunik, Michael G; Tzimenatos, Leah; Vitale, Melissa; Dean, J Michael; Ramilo, Octavio
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 degrees 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 15 with urinary tract infections-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 vs 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.
PMCID:5122927
PMID: 27552618
ISSN: 1538-3598
CID: 2221122

Relationship of Physician-Identified Patient Race and Ethnicity to Use of Computed Tomography in Pediatric Blunt Torso Trauma

Natale, JoAnne E; Joseph, Jill G; Rogers, Alexander J; Tunik, Michael; Monroe, David; Kerrey, Benjamin; Bonsu, Bema K; Cook, Lawrence J; Page, Kent; Adelgais, Kathleen; Quayle, Kimberly; Kuppermann, Nathan; Holmes, James F
OBJECTIVE: To determine whether a child's race or ethnicity as determined by the treating physician is independently associated with receiving abdominal computed tomography (CT) after blunt torso trauma. METHODS: We performed a planned secondary analysis of a prospective observational cohort of children < 18 years old presenting within 24 hours of blunt torso trauma to 20 North American emergency departments participating in a pediatric research network, 2007-2010. Treating physicians documented race/ethnicity as white non-Hispanic, black non-Hispanic, or Hispanic. Using a previously-derived clinical prediction rule, we classified each child's risk for having an intra-abdominal injury undergoing acute intervention to define injury severity. We performed multivariable analyses using generalized estimating equations to control for confounding and for clustering of children within hospitals. RESULTS: Among 12,044 enrolled patients, treating physicians documented race/ethnicity as white non-Hispanic (n=5,847, 54.0%), black non-Hispanic (n=3,687, 34.1%), or Hispanic of any race (n=1,291, 11.9%). Overall, 51.8% of white non-Hispanic, 32.7% of black non-Hispanic, and 44.2% of Hispanic children underwent abdominal CT imaging. After adjusting for age, sex, abdominal ultrasound use, risk for intra-abdominal injury undergoing acute intervention, and hospital clustering, the likelihood of receiving an abdominal CT was lower (odds ratio 0.8, 95% confidence interval 0.7, 0.9) for black non-Hispanic than for white non-Hispanic children. For Hispanic children, the likelihood of receiving an abdominal CT did not differ from that observed in white non-Hispanic children (odds ratio 0.9, 95% confidence interval 0.8, 1.1). CONCLUSIONS: After blunt torso trauma, pediatric patients identified by the treating physicians as black non-Hispanic were less likely to receive abdominal CT imaging than those identified as white non-Hispanic. This suggests that non-clinical factors influence clinician decision-making regarding use of abdominal CT in children. Further studies should focus on explaining how patient race can affect provider choices regarding emergency department radiographic imaging
PMID: 26914184
ISSN: 1553-2712
CID: 1965482

Comparison of Clinician Suspicion Versus a Clinical Prediction Rule in Identifying Children at Risk for Intra-abdominal Injuries After Blunt Torso Trauma

Mahajan, Prashant; Kuppermann, Nathan; Tunik, Michael; Yen, Kenneth; Atabaki, Shireen M; Lee, Lois K; Ellison, Angela M; Bonsu, Bema K; Olsen, Cody S; Cook, Larry; Kwok, Maria Y; Lillis, Kathleen; Holmes, James F
OBJECTIVES: Emergency department (ED) identification and radiographic evaluation of children with intra-abdominal injuries who need acute intervention can be challenging. To date, it is unclear if a clinical prediction rule is superior to unstructured clinician judgment in identifying these children. The objective of this study was to compare the test characteristics of clinician suspicion with a derived clinical prediction rule to identify children at risk of intra-abdominal injuries undergoing acute intervention following blunt torso trauma. METHODS: This was a planned subanalysis of a prospective, multicenter observational study of children (<18 years old) with blunt torso trauma conducted in 20 EDs in the Pediatric Emergency Care Applied Research Network (PECARN). Clinicians documented their suspicion for the presence of intra-abdominal injuries needing acute intervention as <1, 1 to 5, 6 to 10, 11 to 50, or >50% prior to knowledge of abdominal computed tomography (CT) scanning (if performed). Intra-abdominal injuries undergoing acute intervention were defined by a therapeutic laparotomy, angiographic embolization, blood transfusion for abdominal hemorrhage, or intravenous fluid administration for 2 or more days in those with pancreatic or gastrointestinal injuries. Patients were considered to be positive for clinician suspicion if suspicion was documented as >/=1%. Suspicion >/= 1% was compared to the presence of any variable in the prediction rule for identifying children with intra-abdominal injuries undergoing acute intervention. RESULTS: Clinicians recorded their suspicion in 11,919 (99%) of 12,044 patients enrolled in the parent study. Intra-abdominal injuries undergoing acute intervention were diagnosed in 203 (2%) patients. Abdominal CT scans were obtained in the ED in 2,302 of the 2,667 (86%, 95% confidence interval [CI] = 85% to 88%) enrolled patients with clinician suspicion >/=1% and in 3,016 of the 9,252 (33%, 95% CI = 32% to 34%) patients with clinician suspicion < 1%. Sensitivity of the prediction rule for intra-abdominal injuries undergoing acute intervention (197 of 203; 97.0%, 95% CI = 93.7% to 98.9%) was higher than that of clinician suspicion >/=1% (168 of 203; 82.8%, 95% CI = 76.9% to 87.7%; difference = 14.2%, 95% CI = 8.6% to 20.0%). Specificity of the prediction rule (4,979 of the 11,716; 42.5%, 95% CI = 41.6% to 43.4%), however, was lower than that of clinician suspicion (9,217 of the 11,716, 78.7%, 95% CI = 77.9% to 79.4%; difference = -36.2%, 95% CI = -37.3% to -35.0%). Thirty-five (0.4%, 95% CI = 0.3% to 0.5%) patients with clinician suspicion < 1% had intra-abdominal injuries that underwent acute intervention. CONCLUSIONS: The derived clinical prediction rule had a significantly higher sensitivity, but lower specificity, than clinician suspicion for identifying children with intra-abdominal injuries undergoing acute intervention. The higher specificity of clinician suspicion, however, did not translate into clinical practice, as clinicians frequently obtained abdominal CT scans in patients they considered very low risk. If validated, this prediction rule can assist in clinical decision-making around abdominal CT use in children with blunt torso trauma.
PMID: 26302354
ISSN: 1553-2712
CID: 1742042

Benefits of Brain Magnetic Resonance Imaging Over Computed Tomography in Children Requiring Emergency Evaluation of Ventriculoperitoneal Shunt Malfunction: Reducing Lifetime Attributable Risk of Cancer

Kim, In; Torrey, Susan B; Milla, Sarah S; Torch, Marisa C; Tunik, Michael G; Foltin, Jessica C
OBJECTIVES: The rapid growth of computed tomography (CT) has resulted in increased concerns of ionizing radiation exposure and its subsequent risk of cancer development. We evaluated the impact of a new protocol using rapid sequence magnetic resonance imaging (rsMRI) instead of CT in children presenting with possible ventriculoperitoneal shunt (VPS) malfunction to promote patient safety. METHODS: This is a retrospective case series of pediatric patients who received a neuroimaging study for emergency evaluation of possible VPS malfunction at New York University's Tisch Hospital Emergency Department between January 2010 and July 2011. Radiology Charge Master was queried to identify the patient database. The trend in the use of rsMRI and CT was calculated for 3 patient age groups and compared across 3 chronological intervals. The effective dose of ionizing radiation per CT scan was calculated using the CT dose index and dose-length product for each patient. RESULTS: Total of 365 patients with the mean age of 8.87 years received either rsMRI or CT study during the study period. One hundred forty-four of these patients required the imaging studies because of VPS malfunction. Overall, 62% of all VPS malfunction cases used rsMRI instead of CT. The ratio of the number of patients receiving rsMRI divided by CT studies has progressively increased from 1.4:1 to 2.1:1 over 3 chronologic periods. CONCLUSIONS: Children with VPS are subject to multiple neuroimaging studies throughout their lifetime. Rapid sequence MRI is an effective alternative to CT while providing no ionizing radiation exposure or risk of developing radiation-induced cancer.
PMID: 25188755
ISSN: 0749-5161
CID: 1180992

Headache in Traumatic Brain Injuries From Blunt Head Trauma

Dayan, Peter S; Holmes, James F; Hoyle, John Jr; Atabaki, Shireen; Tunik, Michael G; Lichenstein, Richard; Miskin, Michelle; Kuppermann, Nathan
OBJECTIVE: To determine the risk of traumatic brain injuries (TBIs) in children with headaches after minor blunt head trauma, particularly when the headaches occur without other findings suggestive of TBIs (ie, isolated headaches). METHODS: This was a secondary analysis of a prospective observational study of children 2 to 18 years with minor blunt head trauma (ie, Glasgow Coma Scale scores of 14-15). Clinicians assessed the history and characteristics of headaches at the time of initial evaluation, and documented findings onto case report forms. Our outcome measures were (1) clinically important TBI (ciTBI) and (2) TBI visible on computed tomography (CT). RESULTS: Of 27 495 eligible patients, 12 675 (46.1%) had headaches. Of the 12 567 patients who had complete data, 2462 (19.6%) had isolated headaches. ciTBIs occurred in 0 of 2462 patients (0%; 95% confidence interval [CI]: 0%-0.1%) in the isolated headache group versus 162 of 10 105 patients (1.6%; 95% CI: 1.4%-1.9%) in the nonisolated headache group (risk difference, 1.6%; 95% CI: 1.3%-1.9%). TBIs on CT occurred in 3 of 456 patients (0.7%; 95% CI: 0.1%-1.9%) in the isolated headache group versus 271 of 6089 patients (4.5%; 95% CI: 3.9%-5.0%) in the nonisolated headache group (risk difference, 3.8%; 95% CI: 2.3%-4.5%). We found no significant independent associations between the risk of ciTBI or TBI on CT with either headache severity or location. CONCLUSIONS: ciTBIs are rare and TBIs on CT are very uncommon in children with minor blunt head trauma when headaches are their only sign or symptom.
PMID: 25647678
ISSN: 0031-4005
CID: 1456502

Food poisoning

Chapter by: Tunik, Michael G
in: Goldfrank's toxicologic emergencies by Hoffman, Robert S; Howland, Mary Ann; Lewin, Neal A; Nelson, Lewis; Goldfrank, Lewis R; Flomenbaum, Neal [Eds]
New York : McGraw-Hill Education, [2015]
pp. ?-?
ISBN: 0071801847
CID: 2505732

Association of Traumatic Brain Injuries With Vomiting in Children With Blunt Head Trauma

Dayan, Peter S; Holmes, James F; Atabaki, Shireen; Hoyle, John Jr; Tunik, Michael G; Lichenstein, Richard; Alpern, Elizabeth; Miskin, Michelle; Kuppermann, Nathan
STUDY OBJECTIVE: We aimed to determine the prevalence of traumatic brain injuries in children who vomit after minor blunt head trauma, particularly when the vomiting occurs without other findings suggestive of traumatic brain injury (ie, isolated vomiting). We also aimed to determine the relationship between the timing and degree of vomiting and traumatic brain injury prevalence. METHODS: This was a secondary analysis of children younger than 18 years with minor blunt head trauma. Clinicians assessed for history and characteristics of vomiting at the initial evaluation. We assessed for the prevalence of clinically important traumatic brain injury and traumatic brain injury on computed tomography (CT). RESULTS: Of 42,112 children enrolled, 5,557 (13.2%) had a history of vomiting, of whom 815 of 5,392 (15.1%) with complete data had isolated vomiting. Clinically important traumatic brain injury occurred in 2 of 815 patients (0.2%; 95% confidence interval [CI] 0% to 0.9%) with isolated vomiting compared with 114 of 4,577 (2.5%; 95% CI 2.1% to 3.0%) with nonisolated vomiting (difference -2.3%, 95% CI -2.8% to -1.5%). Of patients with isolated vomiting for whom CT was performed, traumatic brain injury on CT occurred in 5 of 298 (1.7%; 95% CI 0.5% to 3.9%) compared with 211 of 3,284 (6.4%; 95% CI 5.6% to 7.3%) with nonisolated vomiting (difference -4.7%; 95% CI -6.0% to -2.4%). We found no significant independent associations between prevalence of clinically important traumatic brain injury and traumatic brain injury on CT with either the timing of onset or time since the last episode of vomiting. CONCLUSION: Traumatic brain injury on CT is uncommon and clinically important traumatic brain injury is very uncommon in children with minor blunt head trauma when vomiting is their only sign or symptom. Observation in the emergency department before determining the need for CT appears appropriate for many of these children.
PMID: 24559605
ISSN: 0196-0644
CID: 900332

Association of patient race/ethnicity with use of computed tomography among children with blunt torso trauma [Meeting Abstract]

Natale, J A; Joseph, J; Rodgers, A; Tunik, M; Monroe, D; Kerrey, B; Bonsu, B; Kent, P; Adelgais, K; Quayle, K; Kuppermann, N; Holmes, J
Background: Recent evidence suggests race and ethnicity are important factors influencing computed tomography (CT) use in children with blunt head trauma. The effect of race and ethnicity on use of abdominal CT in children with blunt torso trauma is unknown. Objectives: To determine if a child's race and/or ethnicity are associated with abdominal CT use after blunt torso trauma. Methods: We performed a planned secondary analysis of a prospective, multicenter observational study conducted by the Pediatric Emergency Care Applied Research Network of children (<18 years old) with blunt torso trauma. The treating physicians documented patient race and ethnicity, and history and physical examination findings. We compared rates of abdominal CT use between patients who were white non-Hispanic, black non-Hispanic, or Hispanic of any race. We used multivariable logistic regression with generalized estimating equations to control for hospital clustering, other patient demographics, and likelihood of intra-abdominal injury undergoing acute intervention based on a previously derived clinical prediction rule. Results: Among 12,044 enrolled patients, 10,825 had race and ethnicity documented as white non-Hispanic, black non-Hispanic, or Hispanic. Overall, 51.8% of white, 32.7% of black, and 44.2% of Hispanic children underwent abdominal CT imaging. After adjusting for possible covariates, the likelihood of receiving an abdominal CT was lower (odds ratio 0.8, 95% confidence interval 0.7, 0.9) for black than for white children. The likelihood of CT use in Hispanic children did not differ from that observed in white non-Hispanic children (odds ratio 0.9, 95% confidence interval 0.8, 1.1). Conclusion: After blunt torso trauma, black non-Hispanic children are less likely to receive abdominal CT imaging. This suggests, as in minor head trauma, that non-clinical factors may influence clinician decision-making regarding use of abdominal CT in children
EMBASE:71469734
ISSN: 1069-6563
CID: 1058382

Chronic hematuria and abdominal pain

Connors, N J; Grino, A; Tunik, M G; Hoffman, R S
Abstract An 18-year-old Asian woman with a history of substance abuse presented to the Emergency Department with right-sided abdominal pain and hematuria of several months duration. Physical examination revealed right upper quadrant and suprapubic tenderness. Liver function tests were normal. Urinalysis showed: large blood, 30-50 red blood cells/high-powered field, and no bacteria. She underwent a CT of the abdomen and pelvis following oral and intravenous contrast.
PMID: 24580064
ISSN: 1556-3650
CID: 829552

"Identification of children at very low risk of clinically-important brain injuries after head trauma: A prospective cohort study": Erratum

Kuppermann, Nathan; Holmes, James F; Dayan, Peter S; Hoyle, John D Jr.; Atabaki, Shireen M; Holubkov, Richard; Nadel, Frances M; Monroe, David; Stanley, Rachel M; Borgialli, Dominic A; Badawy, Mohamed K; Schunk, Jeff E; Quayle, Kimberly S; Mahajan, Prashant; Lichenstein, Richard; Lillis, Kathleen A; Tunik, Michael G; Jacobs, Elizabeth S; Callahan, James M; Gorelick, Marc H; Glass, Todd F; Lee, Lois K; Bachman, Michael C; Cooper, Arthur; Powell, Elizabeth C; Gerardi, Michael J; Melville, Kraig A; Muizelaar, J. Paul; Wisner, David H; Zuspan, Sally Jo; Dean, J. Michael; Wootton-Gorges, Sandra L
Reports an error in "Identification of children at very low risk of clinically-important brain injuries after head trauma: A prospective cohort study" by Nathan Kuppermann, James F. Holmes, Peter S. Dayan, John D. Hoyle Jr., Shireen M. Atabaki, Richard Holubkov, Frances M. Nadel, David Monroe, Rachel M. Stanley, Dominic A. Borgialli, Mohamed K. Badawy, Jeff E. Schunk, Kimberly S. Quayle, Prashant Mahajan, Richard Lichenstein, Kathleen A. Lillis, Michael G. Tunik, Elizabeth S. Jacobs, James M. Callahan, Marc H. Gorelick, Todd F. Glass, Lois K. Lee, Michael C. Bachman, Arthur Cooper, Elizabeth C. Powell, Michael J. Gerardi, Kraig A. Melville, J. Paul Muizelaar, David H. Wisner, Sally Jo Zuspan, J. Michael Dean and Sandra L. Wootton-Gorges (The Lancet, 2009[Oct][3], Vol 374[9696], 1160-1170). In the original article, an error in construction of the final analytical database led to the incorrect classification of the mechanism of injury as moderate, rather than severe, for 394 of 42,412 patients. The corrections are present in the erratum. (The following abstract of the original article appeared in record 2009-18411-001). Background: CT imaging of head-injured children has risks of radiation-induced malignancy. Our aim was to identify children at very low risk of clinically-important traumatic brain injuries (ciTBI) for whom CT might be unnecessary. Methods: We enrolled patients younger than 18 years presenting within 24 h of head trauma with Glasgow Coma Scale scores of 14-15 in 25 North American emergency departments. We derived and validated age-specific prediction rules for ciTBI (death from traumatic brain injury, neurosurgery, intubation >24 h, or hospital admission >2 nights). Findings: We enrolled and analysed 42,412 children (derivation and validation populations: 8,502 and 2,216 younger than 2 years, and 25,283 and 6,411 aged 2 years and older). We obtained CT scans on 14,969 (35.3%); ciTBIs occurred in 376 (0.9%), and 60 (0.1%) underwent neurosurgery. In the validation population, the pr!
PSYCH:2014-03712-031
ISSN: 0140-6736
CID: 953382