Correlation between locally versus centrally processed serum procalcitonin during emergency department research evaluation of febrile infants aged 0-60 days.

Introduction: Procalcitonin (PCT) is a useful biomarker in the initial evaluation of febrile infants for serious bacterial infections (SBIs). However, PCT is not always available locally and must at times be frozen and shipped to a reference laboratory for research studies. We sought to compare PCT measured locally versus centrally at a reference laboratory during a research study. Materials and methods: This was a secondary analysis of a multicenter study of febrile infants ≤60 days evaluated for SBIs from June 2016 to April 2019. A PCT cutoff value of 0.5 ng/mL was used to stratify infants at low-versus high-risk of SBIs. Statistical analyses consisted of Spearman's correlation, Bland-Altman difference plotting, Passing-Bablok regression, Deming regression, and Fisher's exact testing at the 0.5 ng/mL threshold. Results: 241 febrile infants had PCT levels measured both locally and at the reference laboratory. PCT levels measured locally on 5 different platforms and from the frozen research samples demonstrated strong Spearman's correlation (ρ = 0.83) and had similar mean PCT values with an average relative difference of 0.02%. Eleven infants with SBIs had PCT values < 0.5 ng/mL in both the clinical and research samples. Six other infants had differences in SBI prediction based on PCT values at the 0.5 ng/mL threshold between the clinical and research platforms. Conclusions: We found no significant differences in detection of febrile infants at high risk for SBI based on locally (on multiple platforms) versus centrally processed PCT. Testing at a central reference laboratory after freezing and shipping is an accurate and reliable alternative for research studies or when rapid turnaround is not required.

PECARN prediction rules for CT imaging of children presenting to the emergency department with blunt abdominal or minor head trauma: a multicentre prospective validation study.

BACKGROUND: The intra-abdominal injury and traumatic brain injury prediction rules derived by the Pediatric Emergency Care Applied Research Network (PECARN) were designed to reduce inappropriate use of CT in children with abdominal and head trauma, respectively. We aimed to validate these prediction rules for children presenting to emergency departments with blunt abdominal or minor head trauma. METHODS: For this prospective validation study, we enrolled children and adolescents younger than 18 years presenting to six emergency departments in Sacramento (CA), Dallas (TX), Houston (TX), San Diego (CA), Los Angeles (CA), and Oakland (CA), USA between Dec 27, 2016, and Sept 1, 2021. We excluded patients who were pregnant or had pre-existing neurological disorders preventing examination, penetrating trauma, injuries more than 24 h before arrival, CT or MRI before transfer, or high suspicion of non-accidental trauma. Children presenting with blunt abdominal trauma were enrolled into an abdominal trauma cohort, and children with minor head trauma were enrolled into one of two age-segregated minor head trauma cohorts (younger than 2 years vs aged 2 years and older). Enrolled children were clinically examined in the emergency department, and CT scans were obtained at the attending clinician's discretion. All enrolled children were evaluated against the variables of the pertinent PECARN prediction rule before CT results were seen. The primary outcome of interest in the abdominal trauma cohort was intra-abdominal injury undergoing acute intervention (therapeutic laparotomy, angiographic embolisation, blood transfusion, intravenous fluid for ≥2 days for pancreatic or gastrointestinal injuries, or death from intra-abdominal injury). In the age-segregated minor head trauma cohorts, the primary outcome of interest was clinically important traumatic brain injury (neurosurgery, intubation for >24 h for traumatic brain injury, or hospital admission ≥2 nights for ongoing symptoms and CT-confirmed traumatic brain injury; or death from traumatic brain injury). FINDINGS: 7542 children with blunt abdominal trauma and 19 999 children with minor head trauma were enrolled. The intra-abdominal injury rule had a sensitivity of 100·0% (95% CI 98·0-100·0; correct test for 145 of 145 patients with intra-abdominal injury undergoing acute intervention) and a negative predictive value (NPV) of 100·0% (95% CI 99·9-100·0; correct test for 3488 of 3488 patients without intra-abdominal injuries undergoing acute intervention). The traumatic brain injury rule for children younger than 2 years had a sensitivity of 100·0% (93·1-100·0; 42 of 42) for clinically important traumatic brain injuries and an NPV of 100·0%; 99·9-100·0; 2940 of 2940), whereas the traumatic brain injury rule for children aged 2 years and older had a sensitivity of 98·8% (95·8-99·9; 168 of 170) and an NPV of 100·0% (99·9-100·0; 6015 of 6017). The two children who were misclassified by the traumatic brain injury rule were admitted to hospital for observation but did not need neurosurgery. INTERPRETATION: The PECARN intra-abdominal injury and traumatic brain injury rules were validated with a high degree of accuracy. Their implementation in paediatric emergency departments can therefore be considered a safe strategy to minimise inappropriate CT use in children needing high-quality care for abdominal or head trauma. FUNDING: The Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Leukopenia, neutropenia, and procalcitonin levels in young febrile infants with invasive bacterial infections.

BACKGROUND AND OBJECTIVE: Serum procalcitonin (PCT) is a highly accurate biomarker for stratifying the risk of invasive bacterial infections (IBIs) in febrile infants ≤60 days old. However, PCT is unavailable in some settings. We explored the association of leukopenia and neutropenia with IBIs in non-critically ill febrile infants ≤60 days old, with and without PCT. METHODS: We conducted a secondary analysis of a prospective observational cohort consisting of 7407 non-critically ill infants ≤60 days old with temperatures ≥38°C. We focused on the risk of IBIs in patients with leukopenia (white blood cell [WBC] count <5000 cells/µL) or neutropenia (absolute neutrophil count [ANC] <1000 cells/µL), categorized to extremes of lower values, and the impact of PCT on these associations. Multiple logistic regression was used to identify independent predictors of IBIs. RESULTS: Final analysis included 6865 infants with complete data; 45% (3098) had PCT data available. Of the 6865, a total of 111 (1.6%) had bacteremia without bacterial meningitis, 18 (0.3%) had bacterial meningitis without bacteremia, and 19 (0.3%) had both bacteremia and bacterial meningitis. IBI was present in four of 20 (20%) infants with WBC counts ≤2500 cells/µL and four of 311 (1.3%) with ANC <1000 cells/µL. In multivariable logistic regression analysis not including PCT, a WBC count <2500 cells/µL was significantly associated with IBI (OR 13.48, 95% CI 2.92-45.35). However, no patients with leukopenia or neutropenia and PCT ≤0.5 ng/mL had IBIs. CONCLUSIONS: Leukopenia ≤2500 cells/µL in febrile infants ≤60 days old is associated with IBIs. However, in the presence of normal PCT levels, no patients with leukopenia had IBIs. While this suggests leukopenia ≤2500 cells/µL is a risk factor for IBIs in non-critically ill young febrile infants only when PCT is unavailable or elevated, the overall low frequency of leukopenia in this cohort warrants caution in interpretation, with future validation required.

Household Transmission Dynamics of Asymptomatic SARS-CoV-2-Infected Children: A Multinational, Controlled Case-Ascertained Prospective Study.

BACKGROUND: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. METHODS: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up. RESULTS: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC. CONCLUSIONS: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC.

Presentations and Outcomes Among Infants ≤90 Days With and Without SARS-CoV-2.

OBJECTIVES: To compare symptoms and outcomes among infants aged ≤90 days tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a broad, international sample of emergency departments (EDs). METHODS: This was a secondary analysis of infants aged 0 to 90 days with suspected SARS-CoV-2 infections tested using molecular approaches and with 14-day follow-up. The parent studies were conducted at 41 EDs in 10 countries (the global Pediatric Emergency Research Network; March 2020-June 2021) and 14 EDs across Canada (Pediatric Emergency Research Canada network; August 2020-February 2022). Symptom profiles included presence and number of presenting symptoms. Clinical outcomes included hospitalization, ICU admission, and severe outcomes (a composite of intensive interventions, severe organ impairment, or death). RESULTS: Among 1048 infants tested for SARS-CoV-2, 1007 (96.1%) were symptomatic at presentation and 432 (41.2%) were SARS-CoV-2-positive. A systemic symptom (any of the following: Apnea, drowsiness, irritability, or lethargy) was most common and present in 646 (61.6%) infants, regardless of SARS-CoV-2 status. Although fever and upper respiratory symptoms were more common among SARS-CoV-2-positive infants, dehydration, gastrointestinal, skin, and oral symptoms, and the overall number of presenting symptoms did not differ between groups. Infants with SARS-CoV-2 infections were less likely to be hospitalized (32.9% vs 44.8%; difference -11.9% [95% confidence interval (CI) -17.9% to -6.0%]), require intensive care (1.4% vs 5.0%; difference -3.6% [95% CI -5.7% to -1.6%]), and experience severe outcomes (1.4% vs 5.4%; difference -4.0% [95% CI -6.1% to -1.9%]). CONCLUSIONS: SARS-CoV-2 infections may be difficult to differentiate from similar illnesses among the youngest infants but are generally milder. SARS-CoV-2 testing can help inform clinical management.

Telemedicine vs Telephone Consultations and Medication Prescribing Errors Among Referring Physicians: A Cluster Randomized Crossover Trial.

Importance: Critically ill children presenting to emergency departments (EDs) in non-children's hospitals are at high risk for experiencing medical errors, including medication errors. Video telemedicine consultations with pediatric specialists have the potential to reduce the risk of medication errors beyond the current standard of care, telephone consultations. Objective: To compare the rates of ED physician-related medication errors among critically ill children randomized to receive either video telemedicine or telephone consultations. Design, Setting, and Participants: This cluster randomized, unbalanced crossover trial was conducted at 15 community EDs in northern California between September 2014 and March 2018. Analyses were conducted from May 2022 to January 2023. Participants included acutely ill children younger than 15 years presenting to a participating ED. Interventions: Participating EDs were randomized to use video telemedicine or telephone for consultations with pediatric critical care physicians according to 1 of 4 unbalanced (3 telemedicine to 1 telephone) crossover treatment assignment sequences. Main Outcomes and Measures: Pharmacists reviewed medical records to document physician-related medication errors using a previously validated instrument. Multilevel logistic regression analyses were performed to create models with the medication order as the unit of analysis and adjusting for age, the log-transformed Revised Pediatric Emergency Assessment Tool score, and hospital study period. Results: A total of 696 patient encounters were included in the trial (mean [SD] age, 4.2 [4.6] years; median [IQR] age, 2.1 [0.5-2.1] years; 304 female [43.7%]), with 537 patient encounters (77.2%) assigned to video telemedicine and 159 patient encounters (22.8%) assigned to telephone. At least 1 physician-related medication error occurred for 87 patients (12.5%), including 20 of 159 patients (12.6%) in the telephone cohort and 67 of 537 patients (12.5%) in the telemedicine cohort. Of the 2414 medication orders, errors occurred in 124 cases (5.1%), including 26 of 513 orders (5.1%) in the telephone cohort and 98 of 1901 orders (5.2%) in the telemedicine cohort. In the multivariable analysis, the adjusted odds ratio of experiencing a medication error among those assigned to telemedicine was 0.86 (95% CI, 0.49-1.52; P = .61). Conclusions and Relevance: This cluster randomized crossover trial found no statistically significant differences in physician-related medication errors between critically ill children assigned to receive telephone consultations vs video telemedicine consultations. Trial Registration: ClinicalTrials.gov Identifier: NCT02877810.

Sepsis epidemiology in Australian and New Zealand children (SENTINEL): protocol for a multicountry prospective observational study.

INTRODUCTION: Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will be prospectively evaluated. Sepsis therapies, quality of care, parental awareness and understanding of sepsis and parent-reported outcome measures will be described. Understanding these aspects of sepsis care is fundamental for the design and conduct of interventional trials to improve childhood sepsis outcomes. METHODS AND ANALYSIS: This prospective observational study will include children up to 18 years of age presenting to 12 emergency departments with suspected sepsis within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand. Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, clinician assessment of severity of disease, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length-of-stay, mortality censored at hospital discharge or 30 days from enrolment (whichever comes first) and parent-reported outcomes 90 days from enrolment. We will use these data to determine sepsis epidemiology based on existing and novel diagnostic criteria. We will also validate existing and novel sepsis risk stratification criteria, characterise antimicrobial stewardship, guideline adherence, cost and report parental awareness and understanding of sepsis and parent-reported outcome measures. ETHICS AND DISSEMINATION: Ethics approval was received from the Royal Children's Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/69948/RCHM-2021). This included incorporated informed consent for follow-up. The findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER: ACTRN12621000920897; Pre-results.

Parent and Clinician Views on Not Using Antibiotics for Mild Community-Acquired Pneumonia.

OBJECTIVES: Preschool-aged children with mild community-acquired pneumonia (CAP) routinely receive antibiotics even though most infections are viral. We sought to identify barriers to the implementation of a "no antibiotic" strategy for mild CAP in young children. METHODS: Qualitative study using semistructured interviews conducted in a large pediatric hospital in the United States from January 2021 to July 2021. Parents of young children diagnosed with mild CAP in the previous 3 years and clinicians practicing in outpatient settings (pediatric emergency department, community emergency department, general pediatrics offices) were included. RESULTS: Interviews were conducted with 38 respondents (18 parents, 20 clinicians). No parent heard of the no antibiotic strategy, and parents varied in their support for the approach. Degree of support related to their desire to avoid unnecessary medications, trust in clinicians, the emotional difficulty of caring for a sick child, desire for relief of suffering, willingness to accept the risk of unnecessary antibiotics, and judgment about the child's illness severity. Eleven (55%) clinicians were familiar with guidelines specifying a no antibiotic strategy. They identified challenges in not using antibiotics, including diagnostic uncertainty, consequences of undertreatment, parental expectations, follow-up concerns, and acceptance of the risks of unnecessary antibiotic treatment of many children if it means avoiding adverse outcomes for some children. CONCLUSIONS: Although both parents and clinicians expressed broad support for the judicious use of antibiotics, pneumonia presents stewardship challenges. Interventions will need to consider the emotional, social, and logistical aspects of managing pneumonia, in addition to developing techniques to improve diagnosis.

Community-Acquired Pneumonia in Children.

ABSTRACT: Community-acquired pneumonia (CAP) is the most common cause of childhood mortality globally. In the United States, CAP is a leading cause of pediatric hospitalization and antibiotic use and is associated with substantial morbidity. There has been a dramatic shift in microbiological etiologies for CAP in children over time as pneumococcal pneumonia has become less common and viral etiologies have become predominant. There is no commonly agreed on approach to the diagnosis of CAP in children. When indicated, antimicrobial treatment should consist of narrow-spectrum antibiotics. In this article, we will describe the current understanding of the microbiological etiologies, clinical presentation, diagnostic approach, risk factors, treatment, and future directions in the diagnosis and management of pediatric CAP.

Stratification of risk for emergent intracranial abnormalities in children with headaches: a Pediatric Emergency Care Applied Research Network (PECARN) study protocol.

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA in children with headaches based on clinically sensible and reliable variables. METHODS AND ANALYSIS: Prospective cohort study of 28 000 children with headaches presenting to any of 18 EDs in the Pediatric Emergency Care Applied Research Network (PECARN). We include children aged 2-17 years with a chief complaint of headache. We exclude children with a clear non-intracranial alternative diagnosis, fever, neuroimaging within previous year, neurological or developmental condition such that patient history or physical examination may be unreliable, Glasgow Coma Scale score<14, intoxication, known pregnancy, history of intracranial surgery, known structural abnormality of the brain, pre-existing condition predisposing to an intracranial abnormality or intracranial hypertension, head injury within 14 days or not speaking English or Spanish. Clinicians complete a standardised history and physical examination of all eligible patients. Primary outcome is the presence of an EIA as determined by neuroimaging or clinical follow-up. We will use binary recursive partitioning and multiple regression analyses to create and internally validate the risk stratification model. ETHICS AND DISSEMINATION: Ethics approval was obtained for all participating sites from the University of Utah single Institutional Review Board. A waiver of informed consent was granted for collection of ED data. Verbal consent is obtained for follow-up contact. Results will be disseminated through international conferences, peer-reviewed publications, and open-access materials.

Rehydration Rates and Outcomes in Overweight Children With Diabetic Ketoacidosis.

BACKGROUND AND OBJECTIVES: The Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis (DKA) (FLUID) Trial found that rapid fluid infusion does not increase the risk of cerebral injury. Concern persists, however, whether fluid rates should be adjusted for overweight or obese patients. We used the FLUID Trial database to evaluate associations between fluid infusion rate and outcomes in these patients. METHODS: We compared children and youth who were overweight, obese, or normal weight, in regard to protocol adherence, mental status changes, time to DKA resolution, and electrolyte abnormalities. We investigated associations between outcomes and the amount of fluid received in these groups. RESULTS: Obese children and youth were more likely to receive fluids at rates slower than dictated by protocol. Overweight and obese children and youth in the fast fluid arms, who received fluids per the study protocol based on their measured weight, had similar rates of mental status changes or clinically apparent cerebral injury as those with normal weights. Risk of hypophosphatemia was increased in those receiving larger initial bolus volumes and reduced in those receiving higher rehydration rates. No other metabolic outcomes were associated with rehydration. CONCLUSIONS: Protocol adherence data in the FLUID Trial suggest that physicians are uncomfortable using weight-based fluid calculations for overweight or obese children. However, higher rates of fluid infusion were not associated with increased risk of mental status changes or cerebral injury, suggesting that physicians should not limit fluid resuscitation in obese children and youth with DKA.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Radiographic pneumonia in young febrile infants presenting to the emergency department: secondary analysis of a prospective cohort study.

OBJECTIVE: The lack of evidence-based criteria to guide chest radiograph (CXR) use in young febrile infants results in variation in its use with resultant suboptimal quality of care. We sought to describe the features associated with radiographic pneumonias in young febrile infants. STUDY DESIGN: Secondary analysis of a prospective cohort study in 18 emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Febrile (≥38°C) infants aged ≤60 days who received CXRs were included. CXR reports were categorised as 'no', 'possible' or 'definite' pneumonia. We compared demographics, clinical signs and laboratory tests among infants with and without pneumonias. RESULTS: Of 2612 infants, 568 (21.7%) had CXRs performed; 19 (3.3%) had definite and 34 (6%) had possible pneumonias. Patients with definite (4/19, 21.1%) or possible (11/34, 32.4%) pneumonias more frequently presented with respiratory distress compared with those without (77/515, 15.0%) pneumonias (adjusted OR 2.17; 95% CI 1.04 to 4.51). There were no differences in temperature or HR in infants with and without radiographic pneumonias. The median serum procalcitonin (PCT) level was higher in the definite (0.7 ng/mL (IQR 0.1, 1.5)) vs no pneumonia (0.1 ng/mL (IQR 0.1, 0.3)) groups, as was the median absolute neutrophil count (ANC) (definite, 5.8 K/mcL (IQR 3.9, 6.9) vs no pneumonia, 3.1 K/mcL (IQR 1.9, 5.3)). No infants with pneumonia had bacteraemia. Viral detection was frequent (no pneumonia (309/422, 73.2%), definite pneumonia (11/16, 68.8%), possible pneumonia (25/29, 86.2%)). Respiratory syncytial virus was the predominant pathogen in the pneumonia groups and rhinovirus in infants without pneumonias. CONCLUSIONS: Radiographic pneumonias were uncommon in febrile infants. Viral detection was common. Pneumonia was associated with respiratory distress, but few other factors. Although ANC and PCT levels were elevated in infants with definite pneumonias, further work is necessary to evaluate the role of blood biomarkers in infant pneumonias.

Emergency Department Pediatric Readiness and Disparities in Mortality Based on Race and Ethnicity.

Importance: Presentation to emergency departments (EDs) with high levels of pediatric readiness is associated with improved pediatric survival. However, it is unclear whether children of all races and ethnicities benefit equitably from increased levels of such readiness. Objective: To evaluate the association of ED pediatric readiness with in-hospital mortality among children of different races and ethnicities with traumatic injuries or acute medical emergencies. Design, Setting, and Participants: This cohort study of children requiring emergency care in 586 EDs across 11 states was conducted from January 1, 2012, through December 31, 2017. Eligible participants included children younger than 18 years who were hospitalized for an acute medical emergency or traumatic injury. Data analysis was conducted between November 2022 and April 2023. Exposure: Hospitalization for acute medical emergency or traumatic injury. Main Outcomes and Measures: The primary outcome was in-hospital mortality. ED pediatric readiness was measured through the weighted Pediatric Readiness Score (wPRS) from the 2013 National Pediatric Readiness Project assessment and categorized by quartile. Multivariable, hierarchical, mixed-effects logistic regression was used to evaluate the association of race and ethnicity with in-hospital mortality. Results: The cohort included 633 536 children (median [IQR] age 4 [0-12] years]). There were 557 537 children (98 504 Black [17.7%], 167 838 Hispanic [30.1%], 311 157 White [55.8%], and 147 876 children of other races or ethnicities [26.5%]) who were hospitalized for acute medical emergencies, of whom 5158 (0.9%) died; 75 999 children (12 727 Black [16.7%], 21 604 Hispanic [28.4%], 44 203 White [58.2%]; and 21 609 of other races and ethnicities [27.7%]) were hospitalized for traumatic injuries, of whom 1339 (1.8%) died. Adjusted mortality of Black children with acute medical emergencies was significantly greater than that of Hispanic children, White children, and of children of other races and ethnicities (odds ratio [OR], 1.69; 95% CI, 1.59-1.79) across all quartile levels of ED pediatric readiness; but there were no racial or ethnic disparities in mortality when comparing Black children with traumatic injuries with Hispanic children, White children, and children of other races and ethnicities with traumatic injuries (OR 1.01; 95% CI, 0.89-1.15). When compared with hospitals in the lowest quartile of ED pediatric readiness, children who were treated at hospitals in the highest quartile had significantly lower mortality in both the acute medical emergency cohort (OR 0.24; 95% CI, 0.16-0.36) and traumatic injury cohort (OR, 0.39; 95% CI, 0.25-0.61). The greatest survival advantage associated with high pediatric readiness was experienced for Black children in the acute medical emergency cohort. Conclusions and Relevance: In this study, racial and ethnic disparities in mortality existed among children treated for acute medical emergencies but not traumatic injuries. Increased ED pediatric readiness was associated with reduced disparities; it was estimated that increasing the ED pediatric readiness levels of hospitals in the 3 lowest quartiles would result in an estimated 3-fold reduction in disparity for pediatric mortality. However, increased pediatric readiness did not eliminate disparities, indicating that organizations and initiatives dedicated to increasing ED pediatric readiness should consider formal integration of health equity into efforts to improve pediatric emergency care.

Liver transaminase concentrations in children with acute SARS-CoV-2 infection.

OBJECTIVE: To evaluate the relationship between SARS-CoV-2 infection and liver injury by comparing transaminase concentrations among children tested for SARS-CoV-2 and other respiratory viruses in pediatric emergency departments. DESIGN & METHODS: Eligible children were <18 years with suspected SARS-CoV-2, tested using molecular approaches in emergency departments between March 7, 2020, and June 15, 2021 (Pediatric Emergency Research Network), and between August 6, 2020, and February 22, 2022 (Pediatric Emergency Research Canada). We compared aspartate (AST) and alanine aminotransferase (ALT) concentrations at presentation for SARS-CoV-2 and other respiratory viruses through a multivariate linear regression model, with the natural log of serum transaminase concentrations as dependent variables. RESULTS: Of 16,892 enrolled children, 2,462 (14.6%) had transaminase concentrations measured; 4318 (25.6%) were SARS-CoV-2 positive, and 3932 (23.3%) were tested for additional respiratory viruses. Among study participants who had additional respiratory virus testing performed, the most frequently identified viruses were enterovirus/rhinovirus [8.7% (343/3,932)], respiratory syncytial virus [4.6% (181/3,932)], and adenovirus [2.6% (103/3,932)]. Transaminase concentrations were elevated in 25.6% (54/211) of children with isolated SARS-CoV-2 detection and 21.6% (117/541) of those with no virus isolated; P = 0.25. In the multivariable model, isolated SARS-CoV-2 detection was not associated with elevated ALT (adjusted geometric mean ratio (IU/L): 0.96; 95%Confidence Interval (CI): 0.84, 1.08) or AST (adjusted geometric mean ratio (IU/L): 1.03; 95%CI: 0.92, 1.16) concentrations, with negative respiratory panel as the referent group. Ninety-day follow-up was completed in 82.2% (3,550/4,318) of SARS-CoV-2 positive children; no cases of new-onset liver disease were reported. CONCLUSION: Among those tested, transaminase concentrations did not vary between SARS-CoV-2-positive children and those with a negative respiratory viral panel. In multivariate analysis, SARS-CoV-2 infection was not associated with increased initial transaminase concentrations compared to other respiratory viruses.

Toward rational use of repeat imaging in children with mild traumatic brain injuries and intracranial injuries.

OBJECTIVE: Limited evidence exists on the utility of repeat neuroimaging in children with mild traumatic brain injuries (mTBIs) and intracranial injuries (ICIs). Here, the authors identified factors associated with repeat neuroimaging and predictors of hemorrhage progression and/or neurosurgical intervention. METHODS: The authors performed a multicenter, retrospective cohort study of children at four centers of the Pediatric TBI Research Consortium. All patients were ≤ 18 years and presented within 24 hours of injury with a Glasgow Coma Scale score of 13-15 and evidence of ICI on neuroimaging. The outcomes of interest were 1) whether patients underwent repeat neuroimaging during index admission, and 2) a composite outcome of progression of previously identified hemorrhage ≥ 25% and/or repeat imaging as an indication for subsequent neurosurgical intervention. The authors performed multivariable logistic regression and report odds ratios and 95% confidence intervals. RESULTS: A total of 1324 patients met inclusion criteria; 41.3% of patients underwent repeat imaging. Repeat imaging was associated with clinical change in 4.8% of patients; the remainder of the imaging tests were for routine surveillance (90.9%) or of unclear prompting (4.4%). In 2.6% of patients, repeat imaging findings were reported as an indication for neurosurgical intervention. While many factors were associated with repeat neuroimaging, only epidural hematoma (OR 3.99, 95% CI 2.22-7.15), posttraumatic seizures (OR 2.95, 95% CI 1.22-7.41), and age ≥ 2 years (OR 2.25, 95% CI 1.16-4.36) were significant predictors of hemorrhage progression and/or neurosurgery. Of patients without any of these risk factors, none underwent neurosurgical intervention. CONCLUSIONS: Repeat neuroimaging was commonly used but uncommonly associated with clinical deterioration. Although several factors were associated with repeat neuroimaging, only posttraumatic seizures, age ≥ 2 years, and epidural hematoma were significant predictors of hemorrhage progression and/or neurosurgery. These results provide the foundation for evidence-based repeat neuroimaging practices in children with mTBI and ICI.

Clinical and Laboratory Predictors of Dehydration Severity in Children With Diabetic Ketoacidosis.

STUDY OBJECTIVE: Our primary objective was to characterize the degree of dehydration in children with diabetic ketoacidosis (DKA) and identify physical examination and biochemical factors associated with dehydration severity. Secondary objectives included describing relationships between dehydration severity and other clinical outcomes. METHODS: In this cohort study, we analyzed data from 753 children with 811 episodes of DKA in the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation Study, a randomized clinical trial of fluid resuscitation protocols for children with DKA. We used multivariable regression analyses to identify physical examination and biochemical factors associated with dehydration severity, and we described associations between dehydration severity and DKA outcomes. RESULTS: Mean dehydration was 5.7% (SD 3.6%). Mild (0 to <5%), moderate (5 to <10%), and severe (≥10%) dehydration were observed in 47% (N=379), 42% (N=343), and 11% (N=89) of episodes, respectively. In multivariable analyses, more severe dehydration was associated with new onset of diabetes, higher blood urea nitrogen, lower pH, higher anion gap, and diastolic hypertension. However, there was substantial overlap in these variables between dehydration groups. The mean length of hospital stay was longer for patients with moderate and severe dehydration, both in new onset and established diabetes. CONCLUSION: Most children with DKA have mild-to-moderate dehydration. Although biochemical measures were more closely associated with the severity of dehydration than clinical assessments, neither were sufficiently predictive to inform rehydration practice.

Bedside exclusion of pulmonary embolism in children without radiation (BEEPER): a national study of the Pediatric Emergency Care Applied Research Network-Study protocol.

Background: The Pulmonary Embolism Rule Out Criteria (PERC) Peds rule, derived from the PERC rule, was derived to estimate a low pretest probability for pulmonary embolism (PE) in children but has not been prospectively validated. Objective: The objective of this study was to present a protocol for an ongoing multicenter prospective observational study that evaluates the diagnostic accuracy of the PERC-Peds rule. Methods: This protocol is identified by the acronym, BEdside Exclusion of Pulmonary Embolism without Radiation in children. The study aims were designed to prospectively validate, or if necessary, refine, the accuracy of PERC-Peds and D-dimer in excluding PE among children with clinical suspicion or testing for PE. Multiple ancillary studies will examine clinical characteristics and epidemiology of the participants. Children aged 4 through 17 years were being enrolled at 21 sites through the Pediatric Emergency Care Applied Research Network (PECARN). Patients taking anticoagulant therapy are excluded. PERC-Peds criteria data, clinical gestalt, and demographic information are collected in real time. The criterion standard outcome is image-confirmed venous thromboembolism within 45 days, determined from independent expert adjudication. We assessed interrater reliability of the PERC-Peds, frequency of PERC-Peds use in routine clinical care, and descriptive characteristics of missed eligible and missed patients with PE. Results: Enrollment is currently 60% complete with an anticipated data lock in 2025. Conclusions: This prospective multicenter observational study will not only test whether a set of simple criteria can safely exclude PE without need for imaging but also provide a resource to fill a critical knowledge gap about clinical characteristics of children with suspected and diagnosed PE.