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Predicting Delayed Shock in Multisystem Inflammatory Disease in Children: A Multicenter Analysis From the New York City Tri-State Region

Levine, Deborah A; Uy, Vincent; Krief, William; Bornstein, Cara; Daswani, Dina; Patel, Darshan; Kriegel, Marni; Jamal, Nazreen; Patel, Kavita; Liang, Tian; Arroyo, Alexander; Strother, Christopher; Lim, Czer Anthoney; Langhan, Melissa L; Hassoun, Ameer; Chamdawala, Haamid; Kaplan, Carl Philip; Waseem, Muhammad; Tay, Ee Tein; Mortel, David; Sivitz, Adam B; Kelly, Christopher; Lee, Horton James; Qiu, Yuqing; Gorelick, Mark; Platt, Shari L; Dayan, Peter
OBJECTIVES/OBJECTIVE:Patients with multisystem inflammatory disease in children (MIS-C) are at risk of developing shock. Our objectives were to determine independent predictors associated with development of delayed shock (≥3 hours from emergency department [ED] arrival) in patients with MIS-C and to derive a model predicting those at low risk for delayed shock. METHODS:We conducted a retrospective cross-sectional study of 22 pediatric EDs in the New York City tri-state area. We included patients meeting World Health Organization criteria for MIS-C and presented April 1 to June 30, 2020. Our main outcomes were to determine the association between clinical and laboratory factors to the development of delayed shock and to derive a laboratory-based prediction model based on identified independent predictors. RESULTS:Of 248 children with MIS-C, 87 (35%) had shock and 58 (66%) had delayed shock. A C-reactive protein (CRP) level greater than 20 mg/dL (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 2.4-12.1), lymphocyte percent less than 11% (aOR, 3.8; 95% CI, 1.7-8.6), and platelet count less than 220,000/uL (aOR, 4.2; 95% CI, 1.8-9.8) were independently associated with delayed shock. A prediction model including a CRP level less than 6 mg/dL, lymphocyte percent more than 20%, and platelet count more than 260,000/uL, categorized patients with MIS-C at low risk of developing delayed shock (sensitivity 93% [95% CI, 66-100], specificity 38% [95% CI, 22-55]). CONCLUSIONS:Serum CRP, lymphocyte percent, and platelet count differentiated children at higher and lower risk for developing delayed shock. Use of these data can stratify the risk of progression to shock in patients with MIS-C, providing situational awareness and helping guide their level of care.
PMID: 36811547
ISSN: 1535-1815
CID: 5433902

Interventions Targeting Racial/Ethnic Disparities in Stroke Prevention and Treatment

Levine, Deborah A; Duncan, Pamela W; Nguyen-Huynh, Mai N; Ogedegbe, Olugbenga G
Systemic racism is a public health crisis. Systemic racism and racial/ethnic injustice produce racial/ethnic disparities in health care and health. Substantial racial/ethnic disparities in stroke care and health exist and result predominantly from unequal treatment. This special report aims to summarize selected interventions to reduce racial/ethnic disparities in stroke prevention and treatment. It reviews the social determinants of health and the determinants of racial/ethnic disparities in care. It provides a focused summary of selected interventions aimed at reducing stroke risk factors, increasing awareness of stroke symptoms, and improving access to care for stroke because these interventions hold the promise of reducing racial/ethnic disparities in stroke death rates. It also discusses knowledge gaps and future directions.
PMCID:7594115
PMID: 33104466
ISSN: 1524-4628
CID: 4683992

A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections

Kuppermann, Nathan; Dayan, Peter S; Levine, Deborah A; Vitale, Melissa; Tzimenatos, Leah; Tunik, Michael G; Saunders, Mary; Ruddy, Richard M; Roosevelt, Genie; Rogers, Alexander J; Powell, Elizabeth C; Nigrovic, Lise E; Muenzer, Jared; Linakis, James G; Grisanti, Kathleen; Jaffe, David M; Hoyle, John D; Greenberg, Richard; Gattu, Rajender; Cruz, Andrea T; Crain, Ellen F; Cohen, Daniel M; Brayer, Anne; Borgialli, Dominic; Bonsu, Bema; Browne, Lorin; Blumberg, Stephen; Bennett, Jonathan E; Atabaki, Shireen M; Anders, Jennifer; Alpern, Elizabeth R; Miller, Benjamin; Casper, T Charles; Dean, J Michael; Ramilo, Octavio; Mahajan, Prashant
Importance/UNASSIGNED:In young febrile infants, serious bacterial infections (SBIs), including urinary tract infections, bacteremia, and meningitis, may lead to dangerous complications. However, lumbar punctures and hospitalizations involve risks and costs. Clinical prediction rules using biomarkers beyond the white blood cell count (WBC) may accurately identify febrile infants at low risk for SBIs. Objective/UNASSIGNED:To derive and validate a prediction rule to identify febrile infants 60 days and younger at low risk for SBIs. Design, Setting, and Participants/UNASSIGNED:Prospective, observational study between March 2011 and May 2013 at 26 emergency departments. Convenience sample of previously healthy febrile infants 60 days and younger who were evaluated for SBIs. Data were analyzed between April 2014 and April 2018. Exposures/UNASSIGNED:Clinical and laboratory data (blood and urine) including patient demographics, fever height and duration, clinical appearance, WBC, absolute neutrophil count (ANC), serum procalcitonin, and urinalysis. We derived and validated a prediction rule based on these variables using binary recursive partitioning analysis. Main Outcomes and Measures/UNASSIGNED:Serious bacterial infection, defined as urinary tract infection, bacteremia, or bacterial meningitis. Results/UNASSIGNED:We derived the prediction rule on a random sample of 908 infants and validated it on 913 infants (mean age was 36 days, 765 were girls [42%], 781 were white and non-Hispanic [43%], 366 were black [20%], and 535 were Hispanic [29%]). Serious bacterial infections were present in 170 of 1821 infants (9.3%), including 26 (1.4%) with bacteremia, 151 (8.3%) with urinary tract infections, and 10 (0.5%) with bacterial meningitis; 16 (0.9%) had concurrent SBIs. The prediction rule identified infants at low risk of SBI using a negative urinalysis result, an ANC of 4090/µL or less (to convert to ×109 per liter, multiply by 0.001), and serum procalcitonin of 1.71 ng/mL or less. In the validation cohort, the rule sensitivity was 97.7% (95% CI, 91.3-99.6), specificity was 60.0% (95% CI, 56.6-63.3), negative predictive value was 99.6% (95% CI, 98.4-99.9), and negative likelihood ratio was 0.04 (95% CI, 0.01-0.15). One infant with bacteremia and 2 infants with urinary tract infections were misclassified. No patients with bacterial meningitis were missed by the rule. The rule performance was nearly identical when the outcome was restricted to bacteremia and/or bacterial meningitis, missing the same infant with bacteremia. Conclusions and Relevance/UNASSIGNED:We derived and validated an accurate prediction rule to identify febrile infants 60 days and younger at low risk for SBIs using the urinalysis, ANC, and procalcitonin levels. Once further validated on an independent cohort, clinical application of the rule has the potential to decrease unnecessary lumbar punctures, antibiotic administration, and hospitalizations.
PMID: 30776077
ISSN: 2168-6211
CID: 3685742

Epidemiology of paediatric trauma presenting to US emergency departments: 2006-2012

Avraham, Jacob B; Bhandari, Misha; Frangos, Spiros G; Levine, Deborah A; Tunik, Michael G; DiMaggio, Charles J
BACKGROUND: Traumatic injury is the leading cause of paediatric morbidity and mortality in the USA. We present updated national data on emergency department (ED) discharges for traumatic injury for a recent 7-year period. METHODS: We conducted a descriptive epidemiological analysis of the Nationwide Emergency Department Sample Survey, the largest and most comprehensive database in the USA, for 2006-2012. Among children and adolescents, we tracked changes in injury mechanism and severity, cost of care, injury intent and the role of trauma centres. RESULTS: There was an 8.3% (95% CI 7.7 to 8.9) decrease in the annual number of ED visits for traumatic injury in children and adolescents over the study period, from 8 557 904 (SE=5861) in 2006 to 7 846 912 (SE=5191) in 2012. The case-fatality rate was 0.04% for all injuries and 3.2% for severely injured children. Children and adolescents with high-mortality injury mechanisms were more than three times more likely to be treated at a level 1 trauma centre (OR=3.5, 95% CI 3.3 to 3.7), but were more no more likely to die (OR=0.96, 95% CI 0.93 to 1.00). Traumatic brain injury diagnoses increased 22.2% (95% CI 20.6 to 23.9) during the study period. Intentional assault accounted for 3% (SE=0.1) of all child and adolescent ED injury discharges and 7.2% (SE=0.3) of discharges among 15-19 year-olds. There was an 11.3% (95% CI 10.0 to 12.6) decline in motor vehicle injuries from 2009 to 2012. The total cost of care was $23 billion (SE=0.01), a 78% increase from 2006 to 2012. CONCLUSIONS: This analysis presents a recent portrait of paediatric trauma across the USA. These analyses indicate the important role and value of trauma centre care for injured children and adolescents, and that the most common causes and mechanisms of injury are preventable.
PMID: 29056586
ISSN: 1475-5785
CID: 2757522

Risk of Bacterial Coinfections in Febrile Infants 60 Days Old and Younger with Documented Viral Infections

Mahajan, Prashant; Browne, Lorin R; Levine, Deborah A; Cohen, Daniel M; Gattu, Rajender; Linakis, James G; Anders, Jennifer; Borgialli, Dominic; Vitale, Melissa; Dayan, Peter S; Casper, T Charles; Ramilo, Octavio; Kuppermann, Nathan
OBJECTIVE:To determine the risk of serious bacterial infections (SBIs) in young febrile infants with and without viral infections. STUDY DESIGN/METHODS:Planned secondary analyses of a prospective observational study of febrile infants 60 days of age or younger evaluated at 1 of 26 emergency departments who did not have clinical sepsis or an identifiable site of bacterial infection. We compared patient demographics, clinical, and laboratory findings, and prevalence of SBIs between virus-positive and virus-negative infants. RESULTS:Of the 4778 enrolled infants, 2945 (61.6%) had viral testing performed, of whom 1200 (48.1%) were virus positive; 44 of the 1200 had SBIs (3.7%; 95% CI, 2.7%-4.9%). Of the 1745 virus-negative infants, 222 had SBIs (12.7%; 95% CI, 11.2%-14.4%). Rates of specific SBIs in the virus-positive group vs the virus-negative group were: UTIs (33 of 1200 [2.8%; 95% CI, 1.9%-3.8%] vs 186 of 1745 [10.7%; 95% CI, 9.2%-12.2%]) and bacteremia (9 of 1199 [0.8%; 95% CI, 0.3%-1.4%] vs 50 of 1743 [2.9%; 95% CI, 2.1%-3.8%]). The rate of bacterial meningitis tended to be lower in the virus-positive group (0.4%) than in the viral-negative group (0.8%); the difference was not statistically significant. Negative viral status (aOR, 3.2; 95% CI, 2.3-4.6), was significantly associated with SBI in multivariable analysis. CONCLUSIONS:Febrile infants ≤60 days of age with viral infections are at significantly lower, but non-negligible risk for SBIs, including bacteremia and bacterial meningitis.
PMID: 30195552
ISSN: 1097-6833
CID: 3278092

Accuracy of Complete Blood Cell Counts to Identify Febrile Infants 60 Days or Younger With Invasive Bacterial Infections

Cruz, Andrea T; Mahajan, Prashant; Bonsu, Bema K; Bennett, Jonathan E; Levine, Deborah A; Alpern, Elizabeth R; Nigrovic, Lise E; Atabaki, Shireen M; Cohen, Daniel M; VanBuren, John M; Ramilo, Octavio; Kuppermann, Nathan
Importance: Clinicians often risk stratify young febrile infants for invasive bacterial infections (IBIs), defined as bacteremia and/or bacterial meningitis, using complete blood cell count parameters. Objective: To estimate the accuracy of individual complete blood cell count parameters to identify febrile infants with IBIs. Design, Setting, and Participants: Planned secondary analysis of a prospective observational cohort study comprising 26 emergency departments in the Pediatric Emergency Care Applied Research Network from 2008 to 2013. We included febrile (>/=38 degrees C), previously healthy, full-term infants younger than 60 days for whom blood cultures were obtained. All infants had either cerebrospinal fluid cultures or 7-day follow-up. Main Outcomes and Measures: We tested the accuracy of the white blood cell count, absolute neutrophil count, and platelet count at commonly used thresholds for IBIs. We determined optimal thresholds using receiver operating characteristic curves. Results: Of 4313 enrolled infants, 1340 (31%; 95% CI, 30% to 32%) were aged 0 to 28 days, 2412 were boys (56%), and 2471 were white (57%). Ninety-seven (2.2%; 95% CI, 1.8% to 2.7%) had IBIs. Sensitivities were low for common complete blood cell count parameter thresholds: white blood cell count less than 5000/microL, 10% (95% CI, 4% to 16%) (to convert to 109 per liter, multiply by 0.001); white blood cell count >/=15000/microL, 27% (95% CI, 18% to 36%); absolute neutrophil count >/=10000/microL, 18% (95% CI, 10% to 25%) (to convert to x 109 per liter, multiply by 0.001); and platelets <100 x 103/microL, 7% (95% CI, 2% to 12%) (to convert to x 109 per liter, multiply by 1). Optimal thresholds for white blood cell count (11600/microL), absolute neutrophil count (4100/microL), and platelet count (362 x 103/microL) were identified in models that had areas under the receiver operating characteristic curves of 0.57 (95% CI, 0.50-0.63), 0.70 (95% CI, 0.64-0.76), and 0.61 (95% CI, 0.55-0.67), respectively. Conclusions and Relevance: No complete blood cell count parameter at commonly used or optimal thresholds identified febrile infants 60 days or younger with IBIs with high accuracy. Better diagnostic tools are needed to risk stratify young febrile infants for IBIs.
PMID: 28892537
ISSN: 2168-6211
CID: 2772392

Vaccine-preventable diseases in pediatric patients: a review of measles, mumps, rubella, and varicella [digest]

Levine, Deborah A; Pade, Kathryn H
Vaccine-preventable diseases such as measles, mumps, rubella, and varicella continue to plague children and adults worldwide. Although public health programs have helped decrease the prevalence and sequelae of these diseases, outbreaks still occur. To limit the spread of these diseases, emergency clinicians must be able to readily identify the characteristic presentations of the rashes associated with measles, rubella, and varicella, as well as the common presenting features associated with mumps. Diagnostic laboratory studies are not usually necessary, as a complete history and physical examination usually lead to an accurate diagnosis. Treatment for these vaccine-preventable diseases usually consists of supportive care, but, in some cases, severe complications and death may occur. This issue provides a review of the clinical features, differential diagnoses, potential complications, and treatment options for measles, mumps, rubella, and varicella. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].
PMID: 28745854
ISSN: 1549-9650
CID: 3201672

Vaccine-Preventable Diseases In Pediatric Patients: A Review Of Measles, Mumps, Rubella, And Varicella

Levine, Deborah A
Vaccine-preventable diseases such as measles, mumps, rubella, and varicella continue to plague children and adults worldwide. Although public health programs have helped decrease the prevalence and sequelae of these diseases, outbreaks still occur. To limit the spread of these diseases, emergency clinicians must be able to readily identify the characteristic presentations of the rashes associated with measles, rubella, and varicella, as well as the common presenting features associated with mumps. Diagnostic laboratory studies are not usually necessary, as a complete history and physical examination usually lead to an accurate diagnosis. Treatment for these vaccine-preventable diseases usually consists of supportive care, but, in some cases, severe complications and death may occur. This issue provides a review of the clinical features, differential diagnoses, potential complications, and treatment options for measles, mumps, rubella, and varicella.
PMID: 27893360
ISSN: 1549-9650
CID: 2327962

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

Bicycle helmets are highly protective against traumatic brain injury within a dense urban setting

Sethi, Monica; Heidenberg, Jessica; Wall, Stephen P; Ayoung-Chee, Patricia; Slaughter, Dekeya; Levine, Deborah A; Jacko, Sally; Wilson, Chad; Marshall, Gary; Pachter, H Leon; Frangos, Spiros G
BACKGROUND: New York City (NYC) has made significant roadway infrastructure improvements, initiated a bicycle share program, and enacted Vision Zero, an action plan to reduce traffic deaths and serious injuries. The objective of this study was to examine whether bicycle helmets offer a protective advantage against traumatic brain injury (TBI) within a contemporary dense urban setting with a commitment to road safety. METHODS: A prospective observational study of injured bicyclists presenting to a Level I trauma centre was performed. All bicyclists arriving within 24h of injury were included. Data were collected between February, 2012 and August, 2014 and included demographics, imaging studies (e.g. computed tomography (CT)), injury patterns, and outcomes including Glasgow Coma Scale (GCS) and Injury Severity Score. RESULTS: Of 699 patients, 273 (39.1%) were wearing helmets at the time of injury. Helmeted bicyclists were more likely to have a GCS of 15 (96.3% [95% Confidence Interval (CI), 93.3-98.2] vs. 87.6 [95% CI, 84.1-90.6]) at presentation. Helmeted bicyclists underwent fewer head CTs (40.3% [95% CI, 34.4-46.4] vs. 52.8% [95% CI, 48.0-57.6]) and were less likely to sustain intracranial injury (6.3% [95% CI, 2.6-12.5] vs. 19.7% [14.7-25.6]), including skull fracture (0.9% [95% CI, 0.0-4.9] vs. 15.3% [95% CI, 10.8-20.7]) and subdural hematoma (0.0% [95% CI, 0.0-3.2] vs. 8.1% [95% CI, 4.9-12.5]). Helmeted bicyclists were significantly less likely to sustain significant TBI, i.e. Head AIS >/=3 (2.6% [95% CI: 0.7-4.5] vs.10.6% [7.6-12.5]). Four patients underwent craniotomy while three died; all were un-helmeted. A multivariable logistic regression model showed that helmeted bicyclists were 72% less likely to sustain TBI compared with un-helmeted bicyclists (Adjusted Odds Ratio 0.28, 95% CI 0.12-0.61). CONCLUSIONS: Despite substantial road safety measures in NYC, the protective impact of simple bicycle helmets in the event of a crash remains significant. A re-assessment of helmet laws for urban bicyclists is advisable to most effectively translate Vision Zero from a political action plan to public safety reality.
PMID: 26254573
ISSN: 1879-0267
CID: 1721522