A rapid host-protein test for differentiating bacterial from viral infection: Apollo diagnostic accuracy study.

Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC). Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up. Results: Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99). Conclusions: MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making.

Enteric Fever in Children: An Epidemiological and Clinical Review of Cases in Southeast Texas.

Extensively drug-resistant (XDR) strains of Salmonella enterica serotype Typhi have emerged in Pakistan and Iraq. We report 13 children with enteric fever in Southeast Texas seen over 3.5 years, of whom 23.1% had XDR isolates.

Gartland classification concordance of supracondylar fractures among pediatric emergency medicine physicians, radiologists, and orthopedic surgeons.

BACKGROUND: The modified Gartland classification is the most widely accepted grading method of supracondylar humeral fractures among orthopedic surgeons and is relevant to identifying fractures that may require surgery. OBJECTIVE: To assess the interobserver reliability of the modified Gartland classification among pediatric radiologists, pediatric orthopedic surgeons, and pediatric emergency medicine physicians. MATERIALS AND METHODS: Elbow radiographs for 100 children with supracondylar humeral fractures were retrospectively independently graded by two pediatric radiologists, two pediatric orthopedic surgeons, and two pediatric emergency medicine physicians using the modified Gartland classification. A third grader of the same subspecialty served as a tie-breaker as needed to reach consensus. Readers were blinded to one another and to the medical record. The modified Gartland grade documented in the medical record by the treating orthopedic provider was used as the reference standard. Interobserver agreement was assessed using kappa statistics. RESULTS: There was substantial interobserver agreement (kappa = 0.77 [95% CI, 0.69-0.85]) on consensus fracture grade between the three subspecialties. Similarly, when discriminating between Gartland type I and higher fracture grades, there was substantial interobserver agreement between specialties (kappa = 0.77 [95% CI, 0.66-0.89]). The grade assigned by pediatric radiologists differed from the reference standard on 15 occasions, pediatric emergency medicine differed on 19 occasions, and pediatric orthopedics differed on 9 occasions. CONCLUSION: The modified Gartland classification for supracondylar humeral fractures is reproducible among pediatric emergency medicine physicians, radiologists, and orthopedic surgeons.

Predicting Serious Bacterial Infections Among Hypothermic Infants in the Emergency Department.

BACKGROUND: There is insufficient evidence to guide the initial evaluation of hypothermic infants. We aimed to evaluate risk factors for serious bacterial infections (SBI) among hypothermic infants presenting to the emergency department (ED). METHODS: We conducted a multicenter case-control study among hypothermic (rectal temperature <36.5°C) infants ≤90 days presenting to the ED who had a blood culture collected. Our outcome was SBI (bacteremia, bacterial meningitis, and/or urinary tract infection). We performed 1:2 matching. Historical, physical examination and laboratory covariables were determined based on the literature review from febrile and hypothermic infants and used logistic regression to identify candidate risk factors. RESULTS: Among 934 included infants, 57 (6.1%) had an SBI. In univariable analyses, the following were associated with SBI: age > 21 days, fever at home or in the ED, leukocytosis, elevated absolute neutrophil count, thrombocytosis, and abnormal urinalysis. Prematurity, respiratory distress, and hypothermia at home were negatively associated with SBI. The full multivariable model exhibited a c-index of 0.91 (95% confidence interval: 0.88-0.94). One variable (abnormal urinalysis) was selected for a reduced model, which had a c-index of 0.82 (95% confidence interval: 0.75-0.89). In a sensitivity analysis among hypothermic infants without fever (n = 22 with SBI among 116 infants), leukocytosis, absolute neutrophil count, and abnormal urinalysis were associated with SBI. CONCLUSIONS: Historical, examination, and laboratory data show potential as variables for risk stratification of hypothermic infants with concern for SBI. Larger studies are needed to definitively risk stratify this cohort, particularly for invasive bacterial infections.

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.

Clinician Management Practices for Infants With Hypothermia in the Emergency Department.

BACKGROUND: Young infants with serious bacterial infections (SBI) or herpes simplex virus (HSV) infections may present to the emergency department (ED) with hypothermia. We sought to evaluate clinician testing and treatment preferences for infants with hypothermia. METHODS: We developed, piloted, and distributed a survey of ED clinicians from 32 US pediatric hospitals between December 2022 to March 2023. Survey questions were related to the management of infants (≤60 days of age) with hypothermia in the ED. Questions pertaining to testing and treatment preferences were stratified by age. We characterized clinician comfort with the management of infants with hypothermia. RESULTS: Of 1935 surveys distributed, 1231 (63.6%) were completed. The most common definition of hypothermia was a temperature of ≤36.0°C. Most respondents (67.7%) could recall caring for at least 1 infant with hypothermia in the previous 6 months. Clinicians had lower confidence in caring for infants with hypothermia compared with infants with fever (P < .01). The proportion of clinicians who would obtain testing was high in infants 0 to 7 days of age (97.3% blood testing for SBI, 79.7% for any HSV testing), but declined for older infants (79.3% for blood testing for SBI and 9.5% for any HSV testing for infants 22-60 days old). A similar pattern was noted for respiratory viral testing, hospitalization, and antimicrobial administration. CONCLUSIONS: Testing and treatment preferences for infants with hypothermia varied by age and frequently reflected observed practices for febrile infants. We identified patterns in management that may benefit from greater research and implementation efforts.

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.

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.

Forgotten Pediatrics: 8 Disturbing Windows on the Past.

The 75 years since Pediatrics was first published has witnessed an explosion of the scientific knowledge base informing child health. Yet, the path leading to the present has not been linear. We examine several articles that illustrate some of the unexpected twists and turns that have characterized our specialty's history. We hope that it will provide a reminder of the ever-changing nature of scientific knowledge and the need to continually re-evaluate how our own cultural assumptions shape medical practice.

A Case of Community-Acquired Tuberculosis in an Infant Presenting with Pneumonia Refractory to Antibiotic Therapy.

Infant tuberculosis (TB) is a rare but potentially deadly infection and difficult to diagnose, especially in infants who may present with non-specific symptoms. Here, we report a case of an United States-born term infant with community-acquired miliary TB and no confirmed TB exposure history. The patient initially presented with respiratory distress at seven weeks of life with chest radiograph showing a right lower lobe (RLL) infiltrate. After failing multiple courses of treatment for community-acquired pneumonia and developing growth faltering, the patient had imaging findings suggestive of TB infection with CNS involvement. The diagnosis of TB was confirmed by QuantiFERON and purified protein derivative (PPD). In infants who fail conventional treatment for bacterial pneumonia, the differential should be broadened to consider alternative etiologies. Additionally, brain imaging should be performed in cases of disseminated TB despite negative cerebrospinal fluid (CSF) studies since these patients are at high risk of central nervous system (CNS) involvement. Topics: Tuberculosis, pneumonia, pediatrics, growth faltering.

Multicenter evaluation of a method to identify delayed diagnosis of diabetic ketoacidosis and sepsis in administrative data.

OBJECTIVES: To derive a method of automated identification of delayed diagnosis of two serious pediatric conditions seen in the emergency department (ED): new-onset diabetic ketoacidosis (DKA) and sepsis. METHODS: Patients under 21 years old from five pediatric EDs were included if they had two encounters within 7 days, the second resulting in a diagnosis of DKA or sepsis. The main outcome was delayed diagnosis based on detailed health record review using a validated rubric. Using logistic regression, we derived a decision rule evaluating the likelihood of delayed diagnosis using only characteristics available in administrative data. Test characteristics at a maximal accuracy threshold were determined. RESULTS: Delayed diagnosis was present in 41/46 (89 %) of DKA patients seen twice within 7 days. Because of the high rate of delayed diagnosis, no characteristic we tested added predictive power beyond the presence of a revisit. For sepsis, 109/646 (17 %) of patients were deemed to have a delay in diagnosis. Fewer days between ED encounters was the most important characteristic associated with delayed diagnosis. In sepsis, our final model had a sensitivity for delayed diagnosis of 83.5 % (95 % confidence interval 75.2-89.9) and specificity of 61.3 % (95 % confidence interval 56.0-65.4). CONCLUSIONS: Children with delayed diagnosis of DKA can be identified by having a revisit within 7 days. Many children with delayed diagnosis of sepsis may be identified using this approach with low specificity, indicating the need for manual case review.

OUTCOMES OF MISSED DIAGNOSIS OF PEDIATRIC APPENDICITIS, NEW-ONSET DIABETIC KETOACIDOSIS, AND SEPSIS IN FIVE PEDIATRIC HOSPITALS.

BACKGROUND: Missed diagnosis can predispose to worse condition-specific outcomes. OBJECTIVE: To determine 90-day complication rates and hospital utilization after a missed diagnosis of pediatric appendicitis, new-onset diabetic ketoacidosis (DKA), and sepsis. METHODS: We evaluated patients under 21 years of age visiting five pediatric emergency departments (EDs) with a study condition. Case patients had a preceding ED visit within 7 days of diagnosis and underwent case review to confirm a missed diagnosis. Control patients had no preceding ED visit. We compared complication rates and utilization between case and control patients after adjusting for age, sex, and insurance. RESULTS: We analyzed 29,398 children with appendicitis, 5366 with DKA, and 3622 with sepsis, of whom 429, 33, and 46, respectively, had a missed diagnosis. Patients with missed diagnosis of appendicitis or DKA had more hospital days and readmissions; there were no significant differences for those with sepsis. Those with missed appendicitis were more likely to have abdominal abscess drainage (adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 2.4-3.6) or perforated appendicitis (aOR 3.1, 95% CI 2.5-3.8). Those with missed DKA were more likely to have cerebral edema (aOR 4.6, 95% CI 1.5-11.3), mechanical ventilation (aOR 13.4, 95% CI 3.8-37.1), or death (aOR 28.4, 95% CI 1.4-207.5). Those with missed sepsis were less likely to have mechanical ventilation (aOR 0.5, 95% CI 0.2-0.9). Other illness complications were not significantly different by missed diagnosis. CONCLUSIONS: Children with delayed diagnosis of appendicitis or new-onset DKA had a higher risk of 90-day complications and hospital utilization than those with a timely diagnosis.

Validation of a multi-analyte immunoassay for distinguishing bacterial vs. viral infections in a pediatric cohort.

BACKGROUND: Clinical presentation of viral and bacterial infections or co-infections overlaps significantly. Pathogen identification is the gold standard for appropriate treatment. Recently, FDA cleared a multivariate index test called MeMed-BV that distinguishes viral and bacterial infections based on the differential expression of 3 host proteins. Here, we sought to validate MeMed-BV immunoassay on MeMed Key analyzer in our pediatric hospital following guidelines from the Clinical and Laboratory Standards Institute. METHODS: The analytical performance of the MeMed-BV test was evaluated with precision (intra- and inter-assay), method comparison and interference studies. The clinical performance (diagnostic sensitivity and specificity) of the MeMed-BV test was assessed by conducting a retrospective cohort study (n = 60) using plasma samples from pediatric patients with acute febrile illness who visited the emergency department of our hospital. RESULTS: MeMed-BV showed acceptable intra- and inter-assay precision with a range of < 3 score units in both the high-score bacterial as well as the low-score viral controls. Diagnostic accuracy studies revealed a sensitivity of 94% and specificity of 88% for identifying bacterial infections or co-infections. Our MeMed-BV results showed an excellent agreement (R = 0.998) with manufacturer's laboratory data and compared well with ELISA studies. Gross hemolysis and icterus did not affect the assay, but gross lipemia showed a considerable bias in samples with moderate likelihood of viral infection. Importantly, the MeMed-BV test performed better than routinely measured infection-related biomarkers like white blood cell counts, procalcitonin and C-reactive protein in classifying bacterial infections. CONCLUSION: MeMed-BV immunoassay demonstrated acceptable analytical performance and is reliable for distinguishing viral and bacterial infections or co-infections in pediatric patients. Future studies are warranted to examine the clinical utility, especially with respect to reducing the need for blood cultures and time to treatment for the patient.

Bacteremia in Pediatric Liver Transplant Recipients.

BACKGROUND: We aimed to determine the frequency of bacteremia, septic shock and bacterial meningitis in pediatric liver transplant recipients (pLTRs) in the outpatient setting and to identify clinical factors associated with bacteremia. METHODS: Multicenter retrospective study of pLTRs evaluated in the emergency department or outpatient clinic between 2010 and 2018 for suspected infection, defined as fever ≥38 °C or a blood culture obtained. We excluded patients with nontransplant immunodeficiency, multiorgan transplants or intestinal failure. The primary outcome was bacteremia; secondary outcomes included fluid-refractory septic shock, bacterial meningitis and antibiotic resistance. The unit of analysis was the encounter. RESULTS: A total of 151 children had 336 encounters for infection evaluation within 2 years of transplant. Of 307 (91.4%) encounters with blood cultures, 17 (5.5%) had bacteremia, with 10 (58.8%) occurring within 3 months of transplant. Fluid-refractory septic shock and bacterial meningitis occurred in 7 of 307 (2.8%) and 0 of 307 encounters, respectively. Factors associated with bacteremia included closer proximity to transplant (<3 months) [odds ratio (OR): 3.6; 95% confidence interval (CI): 1.3-9.8; P = 0 .01], shorter duration of illness (OR: 4.3; 95% CI: 1.5-12.0; P < 0.01) and the presence of a central venous catheter (CVC) (OR: 12.7; 95% CI: 4.4-36.6; P < 0.01). However, 5 (29.4%) encounters with bacteremia had none of these factors. Among Gram-positive pathogens, 1 of 7 (14.2%) isolates were resistant to vancomycin. Among Gram-negative pathogens, 3 of 13 (23.1%) isolates were resistant to 3rd generation cephalosporins. CONCLUSIONS: Bacteremia was an important cause of infection within 2 years of pLTR. Clinical factors increased the risk of bacteremia. Further, large sample studies should derive multivariable models to identify those at high and low risk of bacteremia to optimize antibiotic use.

Diversity among research coordinators in a pediatric emergency medicine research collaborative network.

We conducted a survey study of clinical research coordinators (CRCs) at the member institutions of the Pediatric Emergency Care Applied Research Network, to determine the demographic and linguistic characteristics of CRCs around the network, and any perceived impact of those characteristics on their duties. A total of 53/74 CRCs completed the survey. Most respondents identified as "female," "white," and "not Hispanic/Latino." Most respondents felt that their race/ethnicity and their ability to speak a language other than English would positively impact recruitment. Four female respondents felt that their gender hindered their recruitment efforts and their sense of belonging within the research team.

Identification of delayed diagnosis of paediatric appendicitis in administrative data: a multicentre retrospective validation study.

OBJECTIVE: To derive and validate a tool that retrospectively identifies delayed diagnosis of appendicitis in administrative data with high accuracy. DESIGN: Cross-sectional study. SETTING: Five paediatric emergency departments (EDs). PARTICIPANTS: 669 patients under 21 years old with possible delayed diagnosis of appendicitis, defined as two ED encounters within 7 days, the second with appendicitis. OUTCOME: Delayed diagnosis was defined as appendicitis being present but not diagnosed at the first ED encounter based on standardised record review. The cohort was split into derivation (2/3) and validation (1/3) groups. We derived a prediction rule using logistic regression, with covariates including variables obtainable only from administrative data. The resulting trigger tool was applied to the validation group to determine area under the curve (AUC). Test characteristics were determined at two predicted probability thresholds. RESULTS: Delayed diagnosis occurred in 471 (70.4%) patients. The tool had an AUC of 0.892 (95% CI 0.858 to 0.925) in the derivation group and 0.859 (95% CI 0.806 to 0.912) in the validation group. The positive predictive value (PPV) for delay at a maximal accuracy threshold was 84.7% (95% CI 78.2% to 89.8%) and identified 87.3% of delayed cases. The PPV at a stricter threshold was 94.9% (95% CI 87.4% to 98.6%) and identified 46.8% of delayed cases. CONCLUSIONS: This tool accurately identified delayed diagnosis of appendicitis. It may be used to screen for potential missed diagnoses or to specifically identify a cohort of children with delayed diagnosis.