Epidemiology of brief resolved unexplained events and impact of clinical practice guidelines in general and pediatric emergency departments.

OBJECTIVES: The aim of this study was to describe the incidence of brief resolved unexplained events (BRUEs) and compare the impact of a national clinical practice guideline (CPG) on admission and diagnostic testing practices between general and pediatric emergency departments (EDs). METHODS: Using the Nationwide Emergency Department Sample for 2012-2019, we conducted a cross-sectional study of children <1 year of age with an International Classification of Diseases diagnostic code for BRUE. Population incidence rate was estimated using Centers for Disease Control and Prevention birth data. ED incidence rate was estimated for all ED encounters. We used interrupted time series to evaluate the associated impact of the CPG publication on the outcomes of ED disposition (discharge, admission, and transfer) and electrocardiogram (ECG) use. RESULTS: Of 133,972 encounters for BRUE, 80.0% occurred in general EDs. BRUE population incidence was 4.28 per 1000 live births and the annual incidence remained stable (p = 0.19). BRUE ED incidence was 5.06 per 1000 infant ED encounters (p = 0.14). The impact of the BRUE CPG on admission rates was limited to pediatric EDs (level shift -23.3%, p = 0.002). Transfers from general EDs did not change with the CPG (level shift 2.2%, p = 0.17). After the CPG was published, ECGs increased by 13.7% in pediatric EDs (p = 0.005) but did not change in general EDs (level shift -0.2%, p = 0.82). CONCLUSIONS: BRUEs remain a common pediatric problem at a population level and in EDs. Although a disproportionate number of infants present to general EDs, there is differential uptake of the CPG recommendations between pediatric and general EDs. These findings may support quality improvement opportunities aimed at improving care for these infants and decreasing unnecessary hospital admissions or transfers.

A Novel Risk Score to Guide the Evaluation of Acute Hematogenous Osteomyelitis in Children.

OBJECTIVES: To identify independent predictors of and derive a risk score for acute hematogenous osteomyelitis (AHO) in children. METHODS: We conducted a retrospective matched case-control study of children >90 days to <18 years of age undergoing evaluation for a suspected musculoskeletal (MSK) infection from 2017 to 2019 at 23 pediatric emergency departments (EDs) affiliated with the Pediatric Emergency Medicine Collaborative Research Committee. Cases were identified by diagnosis codes and confirmed by chart review to meet accepted diagnostic criteria for AHO. Controls included patients who underwent laboratory and imaging tests to evaluate for a suspected MSK infection and received an alternate final diagnosis. RESULTS: We identified 1135 cases of AHO matched to 2270 controls. Multivariable logistic regression identified 10 clinical and laboratory factors independently associated with AHO. We derived a 4-point risk score for AHO using (1) duration of illness >3 days, (2) history of fever or highest ED temperature ≥38°C, (3) C-reactive protein >2.0 mg/dL, and (4) erythrocyte sedimentation rate >25 mm per hour (area under the curve: 0.892, 95% confidence interval [CI]: 0.881 to 0.901). Choosing to pursue definitive diagnostics for AHO when 3 or more factors are present maximizes diagnostic accuracy at 84% (95% CI: 82% to 85%), whereas children with 0 factors present are highly unlikely to have AHO (sensitivity: 0.99, 95% CI: 0.98 to 1.00). CONCLUSIONS: We identified 10 predictors for AHO in children undergoing evaluation for a suspected MSK infection in the pediatric ED and derived a novel 4-point risk score to guide clinical decision-making.

Omphalitis: Clinical Presentation and Approach to Evaluation and Management.

ABSTRACT: Omphalitis is an uncommon but potentially serious infection in neonates. Findings include erythema and induration around the umbilical stump, and purulent drainage may be present. Fever and signs of systemic illness may occur, or there may only be signs of localized soft tissue infection. Until recently, there have been very few cohort studies of omphalitis in high-income countries, and no literature was available regarding the incidence of concurrent serious bacterial infection such as meningitis or urinary tract infection. A recent large, multicenter study suggests that most omphalitis presents as localized soft tissue infection, with very low rates of concurrent serious bacterial infection or adverse outcomes. Underlying urachal abnormalities should be considered in the infant with umbilical drainage. Treatment of omphalitis consists primarily of antibiotic administration, with surgical intervention rarely needed. Although antibiotics are typically administered intravenously, there may be a role for oral antibiotics in some lower risk infants with omphalitis.

Diagnostic testing for evaluation of brief resolved unexplained events.

BACKGROUND: Since the publication of the American Academy of Pediatrics (AAP) clinical practice guideline for brief resolved unexplained events (BRUEs), a few small, single-center studies have suggested low yield of diagnostic testing in infants presenting with such an event. We conducted this large retrospective multicenter study to determine the role of diagnostic testing in leading to a confirmatory diagnosis in BRUE patients. METHODS: Secondary analysis from a large multicenter cohort derived from 15 hospitals participating in the BRUE Quality Improvement and Research Collaborative. The study subjects were infants < 1 year of age presenting with a BRUE to the emergency departments (EDs) of these hospitals between October 1, 2015, and September 30, 2018. Potential BRUE cases were identified using a validated algorithm that relies on administrative data. Chart review was conducted to confirm study inclusion/exclusion, AAP risk criteria, final diagnosis, and contribution of test results. Findings were stratified by ED or hospital discharge and AAP risk criteria. For each patient, we identified whether any diagnostic test contributed to the final diagnosis. We distinguished true (contributory) results from false-positive results. RESULTS: Of 2036 patients meeting study criteria, 63.2% were hospitalized, 87.1% qualified as AAP higher risk, and 45.3% received an explanatory diagnosis. Overall, a laboratory test, imaging, or an ancillary test supported the final diagnosis in 3.2% (65/2036, 95% confidence interval [CI] 2.7%-4.4%) of patients. Out of 5163 diagnostic tests overall, 1.1% (33/2897, 95% CI 0.8%-1.5%) laboratory tests and 1.5% (33/2266, 95% CI 1.0%-1.9%) of imaging and ancillary studies contributed to a diagnosis. Although 861 electrocardiograms were performed, no new cardiac diagnoses were identified during the index visit. CONCLUSIONS: Diagnostic testing to explain BRUE including for those with AAP higher risk criteria is low yield and rarely contributes to an explanation. Future research is needed to evaluate the role of testing in more specific, at-risk populations.

Omphalitis and Concurrent Serious Bacterial Infection.

OBJECTIVE: Describe the clinical presentation, prevalence of concurrent serious bacterial infection (SBI), and outcomes among infants with omphalitis. METHODS: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants ≤90 days of age with omphalitis seen in the emergency department from January 1, 2008, to December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized. RESULTS: Among 566 infants (median age 16 days), 537 (95%) were well-appearing, 64 (11%) had fever at home or in the emergency department, and 143 (25%) had reported fussiness or poor feeding. Blood, urine, and cerebrospinal fluid cultures were collected in 472 (83%), 326 (58%), and 222 (39%) infants, respectively. Pathogens grew in 1.1% (95% confidence interval [CI], 0.3%-2.5%) of blood, 0.9% (95% CI, 0.2%-2.7%) of urine, and 0.9% (95% CI, 0.1%-3.2%) of cerebrospinal fluid cultures. Cultures from the site of infection were obtained in 320 (57%) infants, with 85% (95% CI, 80%-88%) growing a pathogen, most commonly methicillin-sensitive Staphylococcus aureus (62%), followed by methicillin-resistant Staphylococcus aureus (11%) and Escherichia coli (10%). Four hundred ninety-eight (88%) were hospitalized, 81 (16%) to an ICU. Twelve (2.1% [95% CI, 1.1%-3.7%]) had sepsis or shock, and 2 (0.4% [95% CI, 0.0%-1.3%]) had severe cellulitis or necrotizing soft tissue infection. There was 1 death. Serious complications occurred only in infants aged <28 days. CONCLUSIONS: In this multicenter cohort, mild, localized disease was typical of omphalitis. SBI and adverse outcomes were uncommon. Depending on age, routine testing for SBI is likely unnecessary in most afebrile, well-appearing infants with omphalitis.

Accuracy of Diagnostic Codes for Identifying Brief Resolved Unexplained Events.

OBJECTIVES: To evaluate International Classification of Diseases, 10th Revision (ICD-10) coding strategies for the identification of patients with a brief resolved unexplained event (BRUE). METHODS: Multicenter retrospective cohort study, including patients aged <1 year with an emergency department (ED) visit between October 1, 2015, and September 30, 2018, and an ICD-10 code for the following: (1) BRUE; (2) characteristics of BRUE; (3) serious underlying diagnoses presenting as a BRUE; and (4) nonserious diagnoses presenting as a BRUE. Sixteen algorithms were developed by using various combinations of these 4 groups of ICD-10 codes. Manual chart review was used to assess the performance of these ICD-10 algorithms for the identification of (1) patients presenting to an ED who met the American Academy of Pediatrics clinical definition for a BRUE and (2) the subset of these patients discharged from the ED or hospital without an explanation for the BRUE. RESULTS: Of 4512 records reviewed, 1646 (36.5%) of these patients met the American Academy of Pediatrics criteria for BRUE on ED presentation, 1016 (61.7%) were hospitalized, and 959 (58.3%) had no explanation on discharge. Among ED discharges, the BRUE ICD-10 code alone was optimal for case ascertainment (sensitivity: 89.8% to 92.8%; positive predictive value: 51.7% to 72.0%). For hospitalized patients, ICD-10 codes related to the clinical characteristics of BRUE are preferred (specificity 93.2%, positive predictive value 32.7% to 46.3%). CONCLUSIONS: The BRUE ICD-10 code and/or the diagnostic codes for the characteristics of BRUE are recommended, but the choice between approaches depends on the investigative purpose and the specific BRUE population and setting of interest.

Neonatal Mastitis and Concurrent Serious Bacterial Infection.

OBJECTIVES: Describe the clinical presentation, prevalence, and outcomes of concurrent serious bacterial infection (SBI) among infants with mastitis. METHODS: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants aged ≤90 days with mastitis who were seen in the emergency department between January 1, 2008, and December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized. RESULTS: Among 657 infants (median age 21 days), 641 (98%) were well appearing, 138 (21%) had history of fever at home or in the emergency department, and 63 (10%) had reported fussiness or poor feeding. Blood, urine, and cerebrospinal fluid cultures were collected in 581 (88%), 274 (42%), and 216 (33%) infants, respectively. Pathogens grew in 0.3% (95% confidence interval [CI] 0.04-1.2) of blood, 1.1% (95% CI 0.2-3.2) of urine, and 0.4% (95% CI 0.01-2.5) of cerebrospinal fluid cultures. Cultures from the site of infection were obtained in 335 (51%) infants, with 77% (95% CI 72-81) growing a pathogen, most commonly methicillin-resistant Staphylococcus aureus (54%), followed by methicillin-susceptible S aureus (29%), and unspecified S aureus (8%). A total of 591 (90%) infants were admitted to the hospital, with 22 (3.7%) admitted to an ICU. Overall, 10 (1.5% [95% CI 0.7-2.8]) had sepsis or shock, and 2 (0.3% [95% CI 0.04-1.1]) had severe cellulitis or necrotizing soft tissue infection. None received vasopressors or endotracheal intubation. There were no deaths. CONCLUSIONS: In this multicenter cohort, mild localized disease was typical of neonatal mastitis. SBI and adverse outcomes were rare. Evaluation for SBI is likely unnecessary in most afebrile, well-appearing infants with mastitis.

Research environment and resources to support pediatric emergency medicine fellow research.

BACKGROUND: There is a need for pediatric emergency medicine (PEM) researchers, but the current state of PEM fellow research training is not well described. We sought to (1) describe resources and gaps in PEM fellowship research training and (2) assess agreement between fellow and program director (PD) perceptions of these in fellow research experience. METHODS: Surveys were distributed electronically to U.S. PEM fellows and PDs from March to April 2020. Fellows and PDs were queried on program research infrastructure and current gaps in fellow research experience. For programs that had at least one fellow and PD response, each fellow response was compared to their PD's corresponding response (reference standard). For each binary survey item, we determined the percent of responses with agreement between the fellow and PD. RESULTS: Of 79 fellowship programs, 70 (89%) were represented with at least one response, including responses from 59 PDs (75%) and 218 fellows (39% of all fellows, representing 80% of programs). Fellows and PDs identified mentorship and faculty engagement as the most important needs for successful fellowship research; for every one fellow there was a median of 0.8 potential faculty mentors in the division. Twenty percent of fellows were not satisfied with mentorship opportunities. There was no association between fellow career research intent (high, defined as ≥20% dedicated time, or low) with current year of training (p = 0.88), program size (p = 0.67), and area of research focus (p = 0.40). Fellows were often unaware of research being performed by division faculty. CONCLUSION: PEM fellows were not consistently aware of resources available to support research training. To better support PEM fellows' research training, many programs may need to expand mentorship and increase fellows' awareness of local and external resources and opportunities.

Predicting Adverse Outcomes for Shiga Toxin-Producing Escherichia coli Infections in Emergency Departments.

OBJECTIVE: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. STUDY DESIGN: We reviewed medical records of children <18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores >13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. RESULTS: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children <5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children <5 years, greatest net benefit was achieved for a threshold probability >26%. CONCLUSIONS: The HUS severity score was able to discriminate between high- and low-risk children <5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.

Invasive Bacterial Infections in Afebrile Infants Diagnosed With Acute Otitis Media.

OBJECTIVES: To determine the prevalence of invasive bacterial infections (IBIs) and adverse events in afebrile infants with acute otitis media (AOM). METHODS: We conducted a 33-site cross-sectional study of afebrile infants ≤90 days of age with AOM seen in emergency departments from 2007 to 2017. Eligible infants were identified using emergency department diagnosis codes and confirmed by chart review. IBIs (bacteremia and meningitis) were determined by the growth of pathogenic bacteria in blood or cerebrospinal fluid (CSF) culture. Adverse events were defined as substantial complications resulting from or potentially associated with AOM. We used generalized linear mixed-effects models to identify factors associated with IBI diagnostic testing, controlling for site-level clustering effect. RESULTS: Of 5270 infants screened, 1637 met study criteria. None of the 278 (0%; 95% confidence interval [CI]: 0%-1.4%) infants with blood cultures had bacteremia; 0 of 102 (0%; 95% CI: 0%-3.6%) with CSF cultures had bacterial meningitis; 2 of 645 (0.3%; 95% CI: 0.1%-1.1%) infants with 30-day follow-up had adverse events, including lymphadenitis (1) and culture-negative sepsis (1). Diagnostic testing for IBI varied across sites and by age; overall, 278 (17.0%) had blood cultures, and 102 (6.2%) had CSF cultures obtained. Compared with infants 0 to 28 days old, older infants were less likely to have blood cultures (P < .001) or CSF cultures (P < .001) obtained. CONCLUSION: Afebrile infants with clinician-diagnosed AOM have a low prevalence of IBIs and adverse events; therefore, outpatient management without diagnostic testing may be reasonable.

Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children aged <18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible. RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/µL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count <250 × 103/µL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/µL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]). CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.

Clinical Practice Guideline: Maintenance Intravenous Fluids in Children.

Maintenance intravenous fluids (IVFs) are used to provide critical supportive care for children who are acutely ill. IVFs are required if sufficient fluids cannot be provided by using enteral administration for reasons such as gastrointestinal illness, respiratory compromise, neurologic impairment, a perioperative state, or being moribund from an acute or chronic illness. Despite the common use of maintenance IVFs, there is high variability in fluid prescribing practices and a lack of guidelines for fluid composition administration and electrolyte monitoring. The administration of hypotonic IVFs has been the standard in pediatrics. Concerns have been raised that this approach results in a high incidence of hyponatremia and that isotonic IVFs could prevent the development of hyponatremia. Our goal in this guideline is to provide an evidence-based approach for choosing the tonicity of maintenance IVFs in most patients from 28 days to 18 years of age who require maintenance IVFs. This guideline applies to children in surgical (postoperative) and medical acute-care settings, including critical care and the general inpatient ward. Patients with neurosurgical disorders, congenital or acquired cardiac disease, hepatic disease, cancer, renal dysfunction, diabetes insipidus, voluminous watery diarrhea, or severe burns; neonates who are younger than 28 days old or in the NICU; and adolescents older than 18 years old are excluded. We specifically address the tonicity of maintenance IVFs in children.The Key Action Statement of the subcommittee is as follows:1A: The American Academy of Pediatrics recommends that patients 28 days to 18 years of age requiring maintenance IVFs should receive isotonic solutions with appropriate potassium chloride and dextrose because they significantly decrease the risk of developing hyponatremia (evidence quality: A; recommendation strength: strong).

Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis.

OBJECTIVE: The goal of this study was to evaluate the effect of antibiotic administration before lumbar puncture on cerebrospinal fluid profiles in children with bacterial meningitis. METHODS: We reviewed the medical records of all children (1 month to 18 years of age) with bacterial meningitis who presented to 20 pediatric emergency departments between 2001 and 2004. Bacterial meningitis was defined by positive cerebrospinal fluid culture results for a bacterial pathogen or cerebrospinal fluid pleocytosis with positive blood culture and/or cerebrospinal fluid latex agglutination results. Probable bacterial meningitis was defined as positive cerebrospinal fluid Gram stain results with negative results of bacterial cultures of blood and cerebrospinal fluid. Antibiotic pretreatment was defined as any antibiotic administered within 72 hours before the lumbar puncture. RESULTS: We identified 231 patients with bacterial meningitis and another 14 with probable bacterial meningitis. Of those 245 patients, 85 (35%) had received antibiotic pretreatment. After adjustment for patient age, duration and severity of illness at presentation, and bacterial pathogen, longer duration of antibiotic pretreatment was not significantly associated with cerebrospinal fluid white blood cell count, cerebrospinal fluid absolute neutrophil count. However, antibiotic pretreatment was significantly associated with higher cerebrospinal fluid glucose and lower cerebrospinal fluid protein levels. Although these effects became apparent earlier, patients with >or=12 hours of pretreatment, compared with patients who either were not pretreated or were pretreated for <12 hours, had significantly higher median cerebrospinal fluid glucose levels (48 mg/dL vs 29 mg/dL) and lower median cerebrospinal fluid protein levels (121 vs 178 mg/dL). CONCLUSIONS: In patients with bacterial meningitis, antibiotic pretreatment is associated with higher cerebrospinal fluid glucose levels and lower cerebrospinal fluid protein levels, although pretreatment does not modify cerebrospinal fluid white blood cell count or absolute neutrophil count results.

Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis.

CONTEXT: Children with cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital and treated with parenteral antibiotics, although few have bacterial meningitis. We previously developed a clinical prediction rule, the Bacterial Meningitis Score, that classifies patients at very low risk of bacterial meningitis if they lack all of the following criteria: positive CSF Gram stain, CSF absolute neutrophil count (ANC) of at least 1000 cells/microL, CSF protein of at least 80 mg/dL, peripheral blood ANC of at least 10,000 cells/microL, and a history of seizure before or at the time of presentation. OBJECTIVE: To validate the Bacterial Meningitis Score in the era of widespread pneumococcal conjugate vaccination. DESIGN, SETTING, AND PATIENTS: A multicenter, retrospective cohort study conducted in emergency departments of 20 US academic medical centers through the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. All children aged 29 days to 19 years who presented at participating emergency departments between January 1, 2001, and June 30, 2004, with CSF pleocytosis (CSF white blood cells > or =10 cells/microL) and who had not received antibiotic treatment before lumbar puncture. MAIN OUTCOME MEASURE: The sensitivity and negative predictive value of the Bacterial Meningitis Score. RESULTS: Among 3295 patients with CSF pleocytosis, 121 (3.7%; 95% confidence interval [CI], 3.1%-4.4%) had bacterial meningitis and 3174 (96.3%; 95% CI, 95.5%-96.9%) had aseptic meningitis. Of the 1714 patients categorized as very low risk for bacterial meningitis by the Bacterial Meningitis Score, only 2 had bacterial meningitis (sensitivity, 98.3%; 95% CI, 94.2%-99.8%; negative predictive value, 99.9%; 95% CI, 99.6%-100%), and both were younger than 2 months old. A total of 2518 patients (80%) with aseptic meningitis were hospitalized. CONCLUSIONS: This large multicenter study validates the Bacterial Meningitis Score prediction rule in the era of conjugate pneumococcal vaccine as an accurate decision support tool. The risk of bacterial meningitis is very low (0.1%) in patients with none of the criteria. The Bacterial Meningitis Score may be helpful to guide clinical decision making for the management of children presenting to emergency departments with CSF pleocytosis.