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Limited data exist to inform antibiotic selection among people with cystic fibrosis (CF) with airway infection by multiple CF-related microorganisms. This study aimed to determine among children with CF co-infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pa) if the addition of anti-MRSA antibiotics to antipseudomonal antibiotic treatment for pulmonary exacerbations (PEx) would be associated with improved clinical outcomes compared with antipseudomonal antibiotics alone.Retrospective cohort study using data from the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. The odds of returning to baseline lung function and having a subsequent PEx requiring intravenous antibiotics were compared between PEx treated with anti-MRSA and antipseudomonal antibiotics and those treated with antipseudomonal antibiotics alone, adjusting for confounding by indication using inverse probability of treatment weighting.943 children with CF co-infected with MRSA and Pa contributed 2,989 PEx for analysis. Of these, 2,331 (78%) PEx were treated with both anti-MRSA and antipseudomonal antibiotics and 658 (22%) PEx were treated with antipseudomonal antibiotics alone. Compared with PEx treated with antipseudomonal antibiotics alone, the addition of anti-MRSA antibiotics to antipseudomonal antibiotic therapy was not associated with a higher odds of returning to ≥90% or ≥100% of baseline lung function or a lower odds of future PEx requiring intravenous antibiotics.Children with CF co-infected with MRSA and Pa may not benefit from the addition of anti-MRSA antibiotics for PEx treatment. Prospective studies evaluating optimal antibiotic selection strategies for PEx treatment are needed to optimize clinical outcomes following PEx treatment.

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Although viral etiologies predominate, antibiotics are frequently prescribed for community-acquired pneumonia (CAP).We evaluated the association between antibiotic use and outcomes among children hospitalized with suspected CAP.We performed a secondary analysis of a prospective cohort of children hospitalized with suspected CAP.The exposure was the receipt of antibiotics in the emergency department (ED).Clinical outcomes included length of stay (LOS), care escalation, postdischarge treatment failure, 30-day ED revisit, and quality-of-life (QoL) measures from a follow-up survey 7-15 days post discharge. To minimize confounding by indication (e.g., radiographic CAP), we performed inverse probability treatment weighting with propensity analyses.Among 523 children, 66% were5 years, 88% were febrile, 55% had radiographic CAP, and 55% received ED antibiotics. The median LOS was 41 h (IQR: 25, 54). After propensity analyses, there were no differences in LOS, escalated care, treatment failure, or revisits between children who received antibiotics and those who did not. Seventy-one percent of patients completed follow-up surveys after discharge. Among 16% of patients with fevers after discharge, the median fever duration was 2 days, and those who received antibiotics had a 37% decrease in the mean number of days with fever (95% confidence interval: 20% and 51%). We found no statistical differences in other QoL measures.

We sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children.We collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were18 years old, had signs or symptoms of, or risk factors for acute SARS-CoV-2 infection, and had nucleic acid testing performed. To determine if SARS-CoV-2 test status was independently associated with corticosteroid administration, we used a multivariable conditional logistic regression model matched by study site to compare treatments administered based on SARS-CoV-2 test and disposition status. This analysis was repeated for the subgroup of study participants who were hospitalized.30.3% (3,121/10,315) of participants were SARS-CoV-2-positive. Although remdesivir was more commonly administered to SARS-CoV-2-positive children, use was infrequent (25/3120 [0.8%] vs 1/7188 [0.01%]; P = .001). Corticosteroid use was less common among SARS-CoV-2-positive children (219/3120 [7.0%] vs 759/7190 [10.6%]; P.001). Among hospitalized children, there were no differences in provision of inotropes, respiratory support, chest drainage or extracorporeal membrane oxygenation between groups. Corticosteroid administration was associated with age, history of asthma, wheezing, study month, hospitalization and intensive care unit admission; it was not associated with a positive SARS-CoV-2 test result overall (aOR: 0.91; 95%CI: 0.74, 1.12) or among the subgroup of those hospitalized (aOR: 1.04; 95%CI: 0.75, 1.44).Few disease-specific treatments are provided to SARS-CoV-2-positive children; clinical trials evaluating therapies in children are urgently needed.

Despite the increased availability of diagnostic tests for respiratory viruses, their clinical utility for children with community-acquired pneumonia (CAP) remains uncertain.To identify patterns of respiratory virus testing across children's hospitals prior to the COVID-19 pandemic and to determine whether hospital-level rates of viral testing were associated with clinical outcomes.Multicenter retrospective cohort study of children hospitalized for CAP at 19 children's hospitals in the United States from 2010-2019.Using a novel method to identify the performance of viral testing, we assessed time trends in the use of viral tests, both overall and stratified by testing method. Adjusted proportions of encounters with viral testing were compared across hospitals and were correlated with length of stay, antibiotic and oseltamivir use, and performance of ancillary laboratory testing.There were 46,038 hospitalizations for non-severe CAP among children without complex chronic conditions. The proportion with viral testing increased from 38.8% to 44.2% during the study period (p .001). Molecular testing increased (27.2% to 40.0%, p .001) and antigen testing decreased (33.2% to 7.8%, p .001). Hospital-specific adjusted proportions of testing ranged from 10.0% to 83.5% and were not associated with length of stay, antibiotic use, or antiviral use. Hospitals that performed more viral testing did not have lower rates of ancillary laboratory testing.Viral testing practices varied widely across children's hospitals and were not associated with clinically important process or outcome measures. Viral testing may not influence clinical management for many children hospitalized with CAP.

BACKGROUNDLower respiratory tract infection (LRTI) is a leading cause of death in children worldwide. LRTI diagnosis is challenging because noninfectious respiratory illnesses appear clinically similar and because existing microbiologic tests are often falsely negative or detect incidentally carried microbes, resulting in antimicrobial overuse and adverse outcomes. Lower airway metagenomics has the potential to detect host and microbial signatures of LRTI. Whether it can be applied at scale and in a pediatric population to enable improved diagnosis and treatment remains unclear.METHODSWe used tracheal aspirate RNA-Seq to profile host gene expression and respiratory microbiota in 261 children with acute respiratory failure. We developed a gene expression classifier for LRTI by training on patients with an established diagnosis of LRTI (n = 117) or of noninfectious respiratory failure (n = 50). We then developed a classifier that integrates the host LRTI probability, abundance of respiratory viruses, and dominance in the lung microbiome of bacteria/fungi considered pathogenic by a rules-based algorithm.RESULTSThe host classifier achieved a median AUC of 0.967 by cross-validation, driven by activation markers of T cells, alveolar macrophages, and the interferon response. The integrated classifier achieved a median AUC of 0.986 and increased the confidence of patient classifications. When applied to patients with an uncertain diagnosis (n = 94), the integrated classifier indicated LRTI in 52% of cases and nominated likely causal pathogens in 98% of those.CONCLUSIONLower airway metagenomics enables accurate LRTI diagnosis and pathogen identification in a heterogeneous cohort of critically ill children through integration of host, pathogen, and microbiome features.FUNDINGSupport for this study was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute (UG1HD083171, 1R01HL124103, UG1HD049983, UG01HD049934, UG1HD083170, UG1HD050096, UG1HD63108, UG1HD083116, UG1HD083166, UG1HD049981, K23HL138461, and 5R01HL155418) as well as by the Chan Zuckerberg Biohub.

BACKGROUND Plasma proadrenomedullin (proADM) is a promising biomarker to predict disease severity in community-acquired pneumonia (CAP). Urinary biomarkers offer advantages over blood, including ease of collection. We evaluated the association between urinary proADM and disease severity in pediatric CAP. METHODS We performed a prospective cohort study of children 3 months to 18 years with CAP. Urinary proADM/creatinine (Cr) was calculated. Disease severity was defined as: mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with supplemental oxygen and complicated pneumonia) and severe (eg, vasopressors and invasive ventilation). Outcomes were examined using logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP. RESULTS Of the 427 children included, higher proADM/Cr was associated with increased odds of severe disease compared with nonsevere disease [suspected CAP, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.003, 1.04); radiographic CAP, OR 1.03 (95% CI 1.01, 1.06)] when adjusted for other covariates. ProADM/Cr had an area under the receiver operating characteristic curve of 0.56 (threshold 0.9 pmol/mg) to differentiate severe from nonsevere disease in suspected CAP and 0.65 in radiographic CAP (threshold 0.82 pmol/mg). Healthy controls had less proADM in their urine (median, 0.61 pmol/mg) compared with suspected (0.87 pmol/mg, P = 0.018) and radiographic (0.73 pmol/mg, P = 0.016) CAP. CONCLUSIONS Urinary proADM/Cr ratio measured at the time of emergency department visit was statistically associated with the development of severe outcomes in children with CAP, with stronger discriminatory performance in radiographic disease.

OBJECTIVES To describe testing and treatment practices for Mycoplasma pneumoniae (Mp) among children hospitalized with community-acquired pneumonia (CAP). METHODS We conducted a retrospective cohort study using the Pediatric Health Information Systems database. We included children 3 months to 18 years old hospitalized with CAP between 2012 and 2018 and excluded children who were transferred from another hospital and those with complex chronic conditions. We examined the proportion of patients receiving Mp testing and macrolide therapy at the hospital level and trends in Mp testing and macrolide prescription over time. At the patient level, we examined differences in demographics, illness severity (eg, blood gas, chest tube placement), and outcomes (eg, ICU admission, length of stay, readmission) among patients with and without Mp testing. RESULTS Among 103 977 children hospitalized with CAP, 17.3% underwent Mp testing and 31.1% received macrolides. We found no correlation between Mp testing and macrolide treatment at the hospital level (R2 = 0.05; P = .11). Patients tested for Mp were more likely to have blood gas analysis (15.8% vs 12.8%; P < .1), chest tube placement (1.4% vs 0.8%; P < .1), and ICU admission (3.1% vs 1.4%; P < .1). Mp testing increased (from 15.8% to 18.6%; P < .001), and macrolide prescription decreased (from 40.9% to 20.6%; P < .001) between 2012 and 2018. CONCLUSIONS Nearly one-third of hospitalized children with CAP received macrolide antibiotics, although macrolide prescription decreased over time. Clinicians were more likely to perform Mp testing in children with severe illness, and Mp testing and macrolide treatment were not correlated at the hospital level.

OBJECTIVE To characterize the outcomes of children with community acquired pneumonia (CAP) across 41 United States hospitals and evaluate factors associated with potentially unnecessary admissions. METHODS We performed a cross-sectional study of patients with CAP from 41 United States pediatric hospitals and evaluated clinical outcomes using a composite ordinal severity outcome: mild-discharged (discharged from the emergency department), mild-admitted (hospitalized without other interventions), moderate (provision of intravenous fluids, supplemental oxygen, broadening of antibiotics, complicated pneumonia, and presumed sepsis) or severe (ICU, positive-pressure ventilation, vasoactive infusion, chest drainage, extracorporeal membrane oxygenation, severe sepsis, or death). Our primary outcome was potentially unnecessary admissions (ie, mild-admitted). Among mild-discharged and mild-admitted patients, we constructed a generalized linear mixed model for mild-admitted severity and assessed the role of fixed (demographics and clinical testing) and random effects (institution) on this outcome. RESULTS Of 125 180 children, 68.3% were classified as mild-discharged, 6.6% as mild-admitted, 20.6% as moderate and 4.5% as severe. Among admitted patients (n = 39 692), 8321 (21%) were in the mild-admitted group, with substantial variability in this group across hospitals (median 19.1%, interquartile range 12.8%–28.4%). In generalized linear mixed models comparing mild-admitted and mild-discharge severity groups, hospital had the greatest contribution to model variability compared to all other variables. CONCLUSIONS One in 5 hospitalized children with CAP do not receive significant interventions. Among patients with mild disease, institutional variation is the most important contributor to predict potentially unnecessary admissions. Improved prognostic tools are needed to reduce potentially unnecessary hospitalization of children with CAP.

BACKGROUND Antibiotics are frequently used for community-acquired pneumonia (CAP), although viral etiologies predominate. We sought to determine factors associated with antibiotic use among children hospitalized with suspected CAP. METHODS We conducted a prospective cohort study of children who presented to the emergency department (ED) and were hospitalized for suspected CAP. We estimated risk factors associated with receipt of ≥1 dose of inpatient antibiotics and a full treatment course using multivariable Poisson regression with an interaction term between chest radiograph (CXR) findings and ED antibiotic use. We performed a subgroup analysis of children with nonradiographic CAP. RESULTS Among 477 children, 60% received inpatient antibiotics and 53% received a full course. Factors associated with inpatient antibiotics included antibiotic receipt in the ED (relative risk 4.33 [95% confidence interval, 2.63–7.13]), fever (1.66 [1.22–2.27]), and use of supplemental oxygen (1.29 [1.11–1.50]). Children with radiographic CAP and equivocal CXRs had an increased risk of inpatient antibiotics compared with those with normal CXRs, but the increased risk was modest when antibiotics were given in the ED. Factors associated with a full course were similar. Among patients with nonradiographic CAP, 29% received inpatient antibiotics, 21% received a full course, and ED antibiotics increased the risk of inpatient antibiotics. CONCLUSIONS Inpatient antibiotic utilization was associated with ED antibiotic decisions, CXR findings, and clinical factors. Nearly one-third of children with nonradiographic CAP received antibiotics, highlighting the need to reduce likely overuse. Antibiotic decisions in the ED were strongly associated with decisions in the inpatient setting, representing a modifiable target for future interventions.

BACKGROUND Several prediction models have been reported to identify patients with radiographic pneumonia, but none have been validated or broadly implemented into practice. We evaluated 5 prediction models for radiographic pneumonia in children. METHODS We evaluated 5 previously published prediction models for radiographic pneumonia (Neuman, Oostenbrink, Lynch, Mahabee-Gittens, and Lipsett) using data from a single-center prospective study of patients 3 months to 18 years with signs of lower respiratory tract infection. Our outcome was radiographic pneumonia. We compared each model’s area under the receiver operating characteristic curve (AUROC) and evaluated their diagnostic accuracy at statistically-derived cutpoints. RESULTS Radiographic pneumonia was identified in 253 (22.2%) of 1142 patients. When using model coefficients derived from the study dataset, AUROC ranged from 0.58 (95% confidence interval, 0.52–0.64) to 0.79 (95% confidence interval, 0.75–0.82). When using coefficients derived from original study models, 2 studies demonstrated an AUROC >0.70 (Neuman and Lipsett); this increased to 3 after deriving regression coefficients from the study cohort (Neuman, Lipsett, and Oostenbrink). Two models required historical and clinical data (Neuman and Lipsett), and the third additionally required C-reactive protein (Oostenbrink). At a statistically derived cutpoint of predicted risk from each model, sensitivity ranged from 51.2% to 70.4%, specificity 49.9% to 87.5%, positive predictive value 16.1% to 54.4%, and negative predictive value 83.9% to 90.7%. CONCLUSIONS Prediction models for radiographic pneumonia had varying performance. The 3 models with higher performance may facilitate clinical management by predicting the risk of radiographic pneumonia among children with lower respiratory tract infection.

Background Although community-acquired pneumonia (CAP) is one of the most common infections in children, no tools exist to risk stratify children with suspected CAP. We developed and validated a prediction model to risk stratify and inform hospitalization decisions in children with suspected CAP. Methods We performed a prospective cohort study of children aged 3 months to 18 years with suspected CAP in a pediatric emergency department. Primary outcome was disease severity, defined as mild (discharge home or hospitalization for 24 hours), or severe (intensive care unit stay for >24 hours, septic shock, vasoactive agents, positive-pressure ventilation, chest drainage, extracorporeal membrane oxygenation, or death). Ordinal logistic regression and bootstrapped backwards selection were used to derive and internally validate our model. Results Of 1128 children, 371 (32.9%) developed moderate disease and 48 (4.3%) severe disease. Severity models demonstrated excellent discrimination (optimism-corrected c-indices of 0.81) and outstanding calibration. Severity predictors in the final model included respiratory rate, systolic blood pressure, oxygenation, retractions, capillary refill, atelectasis or pneumonia on chest radiograph, and pleural effusion. Conclusions We derived and internally validated a score that accurately predicts disease severity in children with suspected CAP. Once externally validated, this score has potential to facilitate management decisions by providing individualized risk estimates that can be used in conjunction with clinical judgment to improve the care of children with suspected CAP.

To evaluate clinical outcomes in young children with acute asthma exacerbations treated with prednisone/prednisolone versus dexamethasone in the primary care setting.Retrospective cohort study of children ages 3-9 years with a primary care clinic visit for asthma and an associated oral corticosteroid (OCS) prescription fill in the Colorado All Payers Claim Database between 2/2013-3/2019. This was a secondary analysis of a dataset extracted to analyze risk of future development of asthma in younger children. The primary outcome was subsequent ED visit or hospital admission for asthma within 2-14 days after the index clinic visit. Demographics and asthma health services characteristics were assessed. Multivariable logistic regression was used to estimate the association between type of OCS prescription filled within 1 day of the index clinic visit and the primary outcome.There were 3236 index clinic visits for asthma for 1918 children during the study period. Sixty-two percent were male and 66% were 3-4 years old. Prednisone/prednisolone accounted for 84% of OCS prescriptions fills within 1 day of the index clinic visit. One percent visited the ED and 1% required hospital admission within 2-14 days. In multivariate analysis, there was no statistical association between type of OCS prescribed and the primary outcome (OR 0.82; 95% CI: 0.37-1.8).There are no differences in clinical outcomes by type of OCS prescribed for acute asthma exacerbations in the primary care setting. Due to better adherence and side effect profile, primary care providers may consider to use dexamethasone as the preferred OCS.

Background Proadrenomedullin (proADM), a vasodilatory peptide with antimicrobial and anti-inflammatory properties, predicts severe outcomes in adults with community-acquired pneumonia (CAP) to a greater degree than C-reactive protein and procalcitonin. We evaluated the ability of proADM to predict disease severity across a range of clinical outcomes in children with suspected CAP. Methods We performed a prospective cohort study of children 3 months to 18 years with CAP in the emergency department. Disease severity was defined as mild (discharged home), mild–moderate (hospitalized but not moderate–severe or severe), moderate–severe (eg, hospitalized with supplemental oxygen, broadening of antibiotics, complicated pneumonia), and severe (eg, vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined using proportional odds logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP. Results Among 369 children, median proADM increased with disease severity (mild: median [IQR], 0.53 [0.43–0.73]; mild–moderate: 0.56 [0.45–0.71]; moderate–severe: 0.61 [0.47–0.77]; severe: 0.70 [0.55–1.04] nmol/L) (P = .002). ProADM was significantly associated with increased odds of developing severe outcomes (suspected CAP: OR, 1.68; 95% CI, 1.2–2.36; radiographic CAP: OR, 2.11; 95% CI, 1.36–3.38) adjusted for age, fever duration, antibiotic use, and pathogen. ProADM had an AUC of 0.64 (95% CI, .56–.72) in those with suspected CAP and an AUC of 0.77 (95% CI, .68–.87) in radiographic CAP. Conclusions ProADM was associated with severe disease and discriminated moderately well children who developed severe disease from those who did not, particularly in radiographic CAP.

Screening for suicidal ideation in the pediatric emergency department (ED) enhances recognition of suicidality among patients presenting with a nonmental health complaint. Little is known about the assessment of suicide risk factors and disposition among these patients. This study aimed to evaluate pediatric ED providers' documentation of suicide risk factors in this population.We performed a retrospective cohort study of patients screening at risk for suicide on the Ask Suicide-Screening Questions tool. Demographic variables and risk factors for youth suicide were extracted from the electronic health record for eligible patients each month from January 1, 2019, to December 31, 2019. We compared risk factors using χ2 or Fisher exact test.In 2019, of the 7484 patients screened for suicide, 524 (7%) had a positive screen. Of 220 patient charts reviewed, no suicide risk factors were documented in 53.6% of encounters, and only 1 risk factor was documented in 18.2% of encounters. Substance use was the most frequently discussed risk factor, documented in 33.6% of encounters. History of nonsuicidal self-injury was documented in 11.8% of visits. Other risk factors were documented in fewer than 10% of at-risk patients.Pediatric ED providers do not routinely document risk factors for suicide in medical patients screening at risk. Although the Ask Suicide-Screening Questions is an important initial screen, a standardized secondary risk factor assessment is necessary for a more complete risk stratification for patients with suicidal ideation.

Pneumonia has a major impact on childhood health and health care costs. This study was designed to obtain contemporary information on the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children from both inpatient and outpatient settings in the USA.We conducted a prospective, multicenter, observational study of CAP among previously healthy children 2 months to 18 years of age in 6 children's hospitals in Ohio from 2015 to 2018. For pathogen detection, nasopharyngeal swabs were collected from all subjects. Blood and pleural fluid cultures were available per standard of care.We enrolled a convenience sample of 441 patients: 380 hospitalized and 61 outpatients. Tachypnea and radiologic findings of consolidation and pleural effusion were more frequent among inpatients than outpatients. A pathogen was detected in 64.6% of patients: viruses in 55.6%, atypical bacteria in 8.8% and pyogenic bacteria in 4.3%. Eighteen (4.1%) patients had both viruses and bacteria detected. Rhinovirus/enterovirus (RV; 18.6%) and respiratory syncytial virus (RSV; 16.8%) were the viruses most frequently detected, and Mycoplasma pneumoniae (8.2%) and Streptococcus pneumoniae (2.3%) were the most common bacteria. Except for S. pneumoniae, which was identified more frequently in inpatients, there were no significant differences between inpatients and outpatients in the proportions of children with specific pathogens detected.Rhinovirus/enterovirus and RSV among viruses and M. pneumoniae and S. pneumoniae among bacteria were the most common pathogens detected in children with CAP. Tachypnea and chest radiographs with consolidation and/or pleural effusion were associated with hospitalization.

OBJECTIVES: Procalcitonin (PCT) is a relatively novel biomarker that may be superior to C-reactive protein (CRP) in identifying bacterial infection. PCT use in pediatric hospitals is relatively unknown. We aimed to evaluate PCT and CRP use, describe PCT testing variability across children’s hospitals, and compare temporal rates of PCT and CRP testing for patients admitted with pneumonia, sepsis, or fever in young infants. METHODS: In this multicenter cohort study, we identified children ≤18 years old hospitalized from 2014–2018 with pneumonia, sepsis, or fever in infants RESULTS: From 2017–2018, PCT testing occurred in 3988 of 34c231 (12%) hospitalizations. Febrile infants had the highest PCT testing proportion (18%), followed by sepsis (15%) and pneumonia (9%). There was across-hospital variability in PCT testing, particularly for febrile infants. Over time, the odds of PCT testing increased at a significantly greater rate than that of CRP. CONCLUSIONS: Despite limited guideline recommendations for PCT testing during the study period, PCT use increased over time with across-hospital variability. For pneumonia and sepsis, given the importance of high-value care, we need to understand the impact of PCT on patient outcomes. With recent guidelines recommending PCT in the evaluation of febrile infants, we identified baseline testing behaviors for future studies on guideline impact.

OBJECTIVE We examined the relationship between recurrent lower respiratory tract infections (LRTI) in young children and subsequent childhood asthma outcomes. METHODS Retrospective cohort study using 2009-2017 Colorado All Payer Claims Database to assess 0- to 2-year-old children with visits due to LRTI and acute gastroenteritis (AGE). The primary exposure was number of LRTI visits prior to 2 years of age. Children with AGE served as the no LRTI comparator group. The primary outcome was incident asthma, defined by ICD-9 (490.XX) or ICD-10 (J45.9XX) codes, in the same children between 3 and 9 years of age. Multivariable accelerated failure time (AFT) models were used to estimate the effect of LRTI visits on median time to asthma diagnosis. Sensitivity analyses were performed using more conservative asthma diagnostic criteria and with hospitalized children only. RESULTS Of 38,441 eligible subjects, 32,729 had ≥1 LRTI and 5,712 had AGE (no LRTI) between 0 and 2 years of age. Children with ≥3 LRTI visits had an 80% decrease in median time to asthma diagnosis relative to those with AGE visits only (time ratio [TR] 0.2; 95% CI 0.16, 0.24). Children with ≥3 LRTI hospitalizations had a 98% reduction in median time to asthma diagnosis relative to those with AGE hospitalizations only (TR 0.02; 95% CI 0.01, 0.07). History of atopy, wheezing, and family history of asthma documented prior to 2 years of age were also associated with earlier asthma diagnosis. CONCLUSIONS Recurrent LRTIs, especially LRTI hospitalizations, before 2 years of age are associated with earlier diagnosis of pediatric asthma.

BACKGROUND Chest radiographs (CXRs) are frequently used in the diagnosis of community-acquired pneumonia (CAP). We sought to construct a predictive model for radiographic CAP based on clinical features to decrease CXR use. METHODS We performed a single-center prospective study of patients 3 months to 18 years of age with signs of lower respiratory infection who received a CXR for suspicion of CAP. We used penalized multivariable logistic regression to develop a full model and bootstrapped backward selection models to develop a parsimonious reduced model. We evaluated model performance at different thresholds of predicted risk. RESULTS Radiographic CAP was identified in 253 (22.2%) of 1142 patients. In multivariable analysis, increasing age, prolonged fever duration, tachypnea, and focal decreased breath sounds were positively associated with CAP. Rhinorrhea and wheezing were negatively associated with CAP. The bootstrapped reduced model retained 3 variables: age, fever duration, and decreased breath sounds. The area under the receiver operating characteristic for the reduced model was 0.80 (95% confidence interval: 0.77–0.84). Of 229 children with a predicted risk of 39%, 140 (61.1%) had CAP (specificity of 90% at a 39% risk threshold). CONCLUSIONS A predictive model including age, fever duration, and decreased breath sounds has excellent discrimination for radiographic CAP. After external validation, this model may facilitate decisions around CXR or antibiotic use in CAP.

BACKGROUND AND OBJECTIVES: Hospital-associated venous thromboembolism (HA-VTE) is a leading cause of preventable in-hospital mortality in adults. Our objective was to describe HA-VTE and evaluate risk factors for its development in adults admitted to a children’s hospital, which has not been previously studied. We also evaluated the performance of commonly used risk assessment tools for HA-VTE. METHODS: A case-control study was performed at a freestanding children’s hospital. Cases of HA-VTE in patients ≥18 years old (2013–2017) and age-matched controls were identified. We extracted patient and HA-VTE characteristics and HA-VTE risk factors on the basis of previous literature. Thrombosis risk assessment was performed retrospectively by using established prospective adult tools (Caprini and Padua scores). RESULTS: Thirty-nine cases and 78 controls were identified. Upper extremities were the most common site of thrombosis (62%). Comorbid conditions were common (91.5%), and malignancy was more common among case patients than controls (P = .04). The presence of a central venous catheter (P < .01), longer length of stay (P < .01), ICU admission (P = .005), and previous admission within 30 days (P = .01) were more common among case patients when compared with controls. Median Caprini score was higher for case patients (P < .01), whereas median Padua score was similar between groups (P = .08). CONCLUSIONS: HA-VTE in adults admitted to children’s hospitals is an important consideration in a growing high-risk patient population. HA-VTE characteristics in our study were more similar to published data in pediatrics.

Background There are no reliable signs or symptoms that differentiate Mycoplasma pneumoniae (Mp) infection in community-acquired pneumonia (CAP) from other etiologies. Additionally, current diagnostic tests do not reliably distinguish between Mp infection and carriage. We previously determined that the measurement of Mp-specific immunoglobulin M antibody-secreting cells (ASCs) by enzyme-linked immunospot assay allowed for differentiation between infection and carriage. Using this new diagnostic test, we aimed to identify clinical and laboratory features associated with Mp infection. Methods This is a prospective cohort study of children, 3–18 years of age, with CAP from 2016 to 2017. Clinical features and biomarkers were compared between Mp-positive and -negative groups by Mann-Whitney U test or Fisher exact test, as appropriate. Area under the receiver operating characteristic curve (AUC) differences and optimal thresholds were determined by using the DeLong test and Youden J statistic, respectively. Results Of 63 CAP patients, 29 were Mp-positive (46%). Mp positivity was statistically associated with older age (median, 8.6 vs 4.7 years), no underlying disease, family with respiratory symptoms, prior antibiotic treatment, prolonged prodromal respiratory symptoms and fever, and extrapulmonary (skin) manifestations. Lower levels of C-reactive protein, white blood cell count, absolute neutrophil count, and procalcitonin (PCT), specifically PCT 5 years (AUC = 0.77), prodromal fever and respiratory symptoms >6 days (AUC = 0.79), and PCT, Community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae (Mp) is difficult to diagnose. A combination of clinical features and biomarkers may aid physicians in identifying patients at high risk for Mp CAP.

BACKGROUND AND OBJECTIVES: The yield of blood cultures in children hospitalized with community-acquired pneumonia (CAP) is low. Characteristics of children at increased risk of bacteremia remain largely unknown. METHODS: We conducted a secondary analysis of a retrospective cohort study of children aged 3 months to 18 years hospitalized with CAP in 6 children’s hospitals from 2007 to 2011. We excluded children with complex chronic conditions and children without blood cultures performed at admission. Clinical, laboratory, microbiologic, and radiologic data were assessed to identify predictors of bacteremia. RESULTS: Among 7509 children hospitalized with CAP, 2568 (34.2%) had blood cultures performed on the first day of hospitalization. The median age was 3 years. Sixty-five children with blood cultures performed had bacteremia (2.5%), and 11 children (0.4%) had bacteremia with a penicillin-nonsusceptible pathogen. The prevalence of bacteremia was increased in children with a white blood cell count >20 × 103 cells per µL (5.4%; 95% confidence interval 3.5%–8.1%) and in children with definite radiographic pneumonia (3.3%; 95% confidence interval 2.4%–4.4%); however, the prevalence of penicillin-nonsusceptible bacteremia was below 1% even in the presence of individual predictors. Among children hospitalized outside of the ICU, the prevalence of contaminated blood cultures exceeded the prevalence of penicillin-nonsusceptible bacteremia. CONCLUSIONS: Although the prevalence of bacteremia is marginally higher among children with leukocytosis or radiographic pneumonia, the rates remain low, and penicillin-nonsusceptible bacteremia is rare even in the presence of these predictors. Blood cultures should not be obtained in children hospitalized with CAP in a non-ICU setting.

Pediatric hospital medicine (PHM) is the newest subspecialty recognized by the American Board of Pediatrics. The academic focus of PHM has largely centered on clinical, educational, and health services research, quality improvement, and advocacy, with a notable paucity of either basic or translational research. Advances in biomedical technology, which are increasingly affordable and accessible, allow for an improved ability to identify specific patient phenotypes, tailor treatments, and identify patients at high risk for poor outcomes. This approach improves the care of hospitalized children, which is an essential aspect of PHM. Accordingly, there is a fundamental need to start building capacity to support and promote basic science and translational research to strengthen the existing evidence base for the management of hospitalized children. A critical first step is providing the education and support necessary to ensure interested hospitalists are able to succeed as physician scientists. In this perspectives piece, we provide our opinion as early- to midcareer researchers engaged in basic science and translational research in PHM. Although there are translational researchers within the PHM community,1–5 there is currently no framework for formal training in basic and translational research within PHM, nor is there precedent in the adult hospitalist community; therefore, PHM has an opportunity to lead the way for developing basic and translational researchers.6 Despite the current absence of formalized training, hospitalists already possess skills that are directly applicable to the translational world. Hospitalists routinely manage the pathologies from multiple organ systems, focus on coordination …

BACKGROUND: The British Thoracic Society (BTS) guideline for pediatric community-acquired pneumonia (CAP) outlines severity criteria to guide clinical decision-making. Our objective was to examine the predictive performance of the criteria on the need for hospitalization (NFH) and disposition. METHODS: This was a retrospective cohort study of children 3 months–18 years of age diagnosed with CAP in an urban, pediatric emergency department (ED) in the United States from September 2014 to August 2015. Children with chronic medical conditions, recent ED visits, and ED transfers were excluded. The main outcomes were interventions or diagnoses that necessitate hospitalization (ie, NFH) and disposition (eg, admit vs. discharge). Test characteristics, stratified by age, were calculated for each outcome. RESULTS: Of 518 eligible children, 56.6% (n = 293) were discharged from the ED with 372 children meeting at least 1 BTS criterion. Overall BTS criteria were specific but not sensitive for NFH nor for disposition. For children 0.60 for both outcomes. The areas under the receiver operator characteristic curves for predicting any BTS criteria was 0.57 for NFH and 0.84 for disposition. CONCLUSIONS: The BTS CAP severity criteria had fair to excellent ability to predict NFH and disposition, respectively. Although specific, the low sensitivity and poor discriminatory ability for NFH of these criteria suggest a need for improved prognostic tools for children with CAP.

Objectives Chest radiographs (CXRs) are often performed in children with respiratory illness to inform the decision to prescribe antibiotics. Our objective was to determine the factors associated with clinicians' plans to treat with antibiotics prior to knowledge of CXR results and the associations between preradiograph plans with antibiotic prescription and return to medical care. Methods Previously healthy children aged 3 months to 18 years with a CXR for suspected pneumonia were enrolled in a prospective cohort study in the emergency department. Our primary outcomes were antibiotic prescription or administration in the emergency department and medical care sought within 7 to 15 days after discharge. Inverse probability treatment weighting was used to limit bias due to treatment selection. Inverse probability treatment weighting was included in a logistic regression model estimating the association between the intention to give antibiotics and outcomes. Results Providers planned to prescribe antibiotics prior to CXR in 68 children (34.9%). There was no difference in the presence of radiographic pneumonia between those with and without a plan for antibiotics. Children who had a plan for antibiotics were more likely to receive antibiotics than those without (odds ratio [OR], 6.39; 95% confidence interval [CI], 3.7-11.0). This association was stronger than the association between radiographic pneumonia and antibiotic receipt (OR, 3.49; 95% CI, 1.98-6.14). Children prescribed antibiotics were more likely to seek care after discharge than children who were not (OR, 1.85; 95% CI, 1.13-3.05). Conclusions Intention to prescribe antibiotics based on clinical impression was the strongest predictor of antibiotic prescription in our study. Prescribing antibiotics may lead to subsequent medical care after controlling for radiographic pneumonia.

In-hospital arrests are uncommon in pediatrics, making it difficult to identify the risk factors for unrecognized deterioration and to determine the effectiveness of rapid response systems. An emergency transfer (ET) is a transfer from an acute care floor to an intensive care unit (ICU) where the patient received intubation, inotropes, or ≥3 fluid boluses in the first hour after arrival or before transfer. Improvement science work has reduced ETs, but ETs have not been validated against important health outcomes. This case–control study aimed to determine the predictive validity of an ET for outcomes in a free-standing children’s hospital. Controls were matched in terms of age, hospital unit, and time of year. Patients who experienced an ET had a significantly higher likelihood of in-hospital mortality (22% vs 9%), longer ICU length of stay (4.9 vs 2.2 days), and longer posttransfer length of stay (26.4 vs 14.7 days) compared with controls (P < .03 for each).

Objectives To compare pediatric emergency clinicians’ attitudes toward three feedback modalities and assess clinicians’ case-based feedback preferences. Methods Electronic survey sent to pediatric emergency medicine (PEM) physicians and fellows; general pediatricians; and advanced practice providers (APPs) with nine questions exploring effectiveness and emotional impact of three feedback modalities: case-based feedback, bounce-back notifications, and biannual performance reports. Additional questions used a four-point ordinal agreement response scale and assessed clinicians’ attitudes toward case review notification, case-based feedback preferences, and emotional support. Survey responses were compared by feedback modality using Pearson’s chi-squared. Results Of 165 eligible providers, 93 (56%) responded. Respondents agreed that case-based feedback was timely (81%), actionable (75%), prompted reflection on decision-making (92%), prompted research on current clinical practice (53%), and encouraged practice change (58%). Pediatric Emergency Care Applied Research Network (PECARN) performance reports scored the lowest on all metrics except positive feedback. No more than 40% of providers indicated that any feedback modality provided emotional support. Regarding case-based feedback, 88% of respondents desired email notification before case review and 88% desired feedback after case review. Clinicians prefer receiving feedback from someone with similar or more experience/training. Clinicians receiving feedback desire succinctness, supporting evidence, consistency, and sensitive delivery. Conclusions Case-based feedback scored highest of the three modalities and is perceived to be the most likely to improve decision-making and promote practice change. Most providers did not perceive emotional support from any feedback modality. Emotional safety warrants purposeful attention in feedback delivery. Critical components of case-based feedback include succinctness, supporting evidence, consistency, and sensitive delivery.

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults and only rarely in children. To investigate whether differences in the upper airway immune response could contribute to this disparity, we compared nasopharyngeal gene expression in 83 children (40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes (ISGs) was robustly activated in both children and adults with SARS-CoV-2 compared to the respective non-viral groups, with only relatively subtle distinctions. Children, however, demonstrated markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including TNF, IFNγ, IL-2 and IL-4 production. Cell type deconvolution confirmed greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibited a decrease in proportions of ciliated cells, the primary target of SARS-CoV-2, upon infection with the virus. These findings demonstrate that children elicit a more robust innate and adaptive immune response to SARS-CoV-2 infection in the upper airway that likely contributes to their protection from severe disease in the lower airway.

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults whereas disease burden in children is lower. To investigate whether differences in the upper airway immune response may contribute to this disparity, we compare nasopharyngeal gene expression in 83 children (40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes is robustly activated in both children and adults with SARS-CoV-2 infection compared to the respective non-viral groups, with only subtle distinctions. Children, however, demonstrate markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including response to TNF and production of IFNγ, IL-2 and IL-4. Cell type deconvolution confirms greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibit a decrease in proportions of ciliated cells, among the primary targets of SARS-CoV-2, upon infection. These findings demonstrate that children elicit a more robust innate and especially adaptive immune response to SARS-CoV-2 in the upper airway that likely contributes to their protection from severe disease in the lower airway.

The human metabolome may vary based on age, over time, and in the presence of viral carriage and bacterial colonization—a common scenario in children. We used nuclear magnetic resonance spectroscopy to identify and quantify urinary metabolites of children without signs or symptoms of respiratory illness. A urine sample and two nasopharyngeal swabs were collected to test for respiratory viral pathogens and colonization by Streptococcus pneumoniae (Sp). Urine samples were collected at the initial visit, 24 h post-enrollment, and 10–14 days post-enrollment. Of the 122 children enrolled, 24% had a virus detected and 19.7% had Sp detected. Intraclass correlation coefficients demonstrated greater within-subject versus between-subject variability for all metabolites detected. In linear mixed models adjusted for age, time, history of asthma, Sp, and viruses, 1-methylnicotinamide was increased by 50% in children with Sp and decreased by 35% in children with rhinovirus/enterovirus. Children with Sp had 83% higher levels of trimethylamine-N-oxide compared with those without Sp. However, when adjusting for multiple comparisons, the association was no longer statistically significant. In conclusion, there appear to be short-term changes within the urinary metabolome of healthy children, but levels of metabolites did not statistically differ in children with viral carriage or Sp detected.

BackgroundLower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children.MethodsWe conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI.FindingsBetween Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92%) children with LRTI, with respiratory syncytial virus (127 [46%]), Haemophilus influenzae (70 [25%]), and Moraxella catarrhalis (65 [24%]) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68%) children without LRTI, with rhinovirus (30 [25%]) being most prevalent. Respiratory syncytial virus (p

We sought to determine whether temporal changes in the lower airway microbiome are associated with ventilator-associated pneumonia (VAP) in children.Using a multicentre prospective study of children aged 31 days to 18 years requiring mechanical ventilation support for >72 h, daily tracheal aspirates were collected and analysed by sequencing of the 16S rRNA gene. VAP was assessed using 2008 Centers for Disease Control and Prevention paediatric criteria. The association between microbial factors and VAP was evaluated using joint longitudinal time-to-event modelling, matched case–control comparisons and unsupervised clustering.Out of 366 eligible subjects, 66 (15%) developed VAP at a median of 5 (interquartile range 3–5) days post intubation. At intubation, there was no difference in total bacterial load (TBL), but Shannon diversity and the relative abundance ofStreptococcus, Lactobacillales andPrevotellawere lower for VAP subjectsversusnon-VAP subjects. However, higher TBL on each sequential day was associated with a lower hazard (hazard ratio 0.39, 95% CI 0.23–0.64) for developing VAP, but sequential values of diversity were not associated with VAP. Similar findings were observed from the matched analysis and unsupervised clustering. The most common dominant VAP pathogens includedPrevotellaspecies (19%),Pseudomonas aeruginosa(14%) andStreptococcus mitis/pneumoniae(10%).MycoplasmaandUreaplasmawere also identified as dominant organisms in several subjects.In mechanically ventilated children, changes over time in microbial factors were marginally associated with VAP risk, although these changes were not suitable for predicting VAP in individual patients. These findings suggest that focusing exclusively on pathogen burden may not adequately inform VAP diagnosis.

Background: There is variability in primary care provider (PCP) oral corticosteroid (OCS) preferences for treatment of children with acute asthma exacerbations. However, the impact of PCP steroid treatment choices on clinical outcomes has not been evaluated. Objective: To evaluate clinical outcomes in children with acute asthma exacerbations treated with prednisone/prednisolone versus dexamethasone at their primary care clinic. Methods: Retrospective cohort study of children ages 3-9 years in the Colorado All Payers Claim Database with a primary care clinic visit for asthma and an associated OCS prescription fill between January 22, 2013 and June 26, 2019. Index clinic …

OBJECTIVES: Many hospitals have transitioned from conventional stool diagnostics to rapid multiplex polymerase chain reaction gastrointestinal panels (GIP). The clinical impact of this testing has not been evaluated in children. In this study, we compare use, results, and patient outcomes between conventional diagnostics and GIP testing. METHODS: This is a multicenter cross-sectional study of children who underwent stool testing from 2013 to 2017. We used bivariate analyses to compare test use, results, and patient outcomes, including length of stay (LOS), ancillary testing, and hospital charges, between the GIP era (24 months after GIP introduction) and conventional diagnostic era (historic control, 24 months before). RESULTS: There were 12 222 tests performed in 8720 encounters. In the GIP era, there was a 21% increase in the proportion of children who underwent stool testing, with a statistically higher percentage of positive results (40% vs 11%), decreased time to result (4 vs 31 hours), and decreased time to treatment (11 vs 35 hours). Although there was a decrease in LOS by 2 days among those who received treatment of a bacterial and/or parasitic pathogen (5.1 vs 3.1; P < .001), this represented only 3% of tested children. In the overall population, there was no statistical difference in LOS, ancillary testing, or charges. CONCLUSIONS: The GIP led to increased pathogen detection and faster results. This translated into improved outcomes for only a small subset of patients, suggesting that unrestricted GIP use leads to low-value care. Similar to other novel rapid diagnostic panels, there is a critical need for diagnostic stewardship to optimize GIP testing.

OBJECTIVES: Validated prognostic tools for pediatric community-acquired pneumonia (CAP) do not exist. Thus, clinicians rely on “gestalt” in management decisions for children with CAP. We sought to determine the ability of clinician gestalt to predict severe outcomes. METHODS: We performed a prospective cohort study of children 3 months to 18 years old presenting to a pediatric emergency department (ED) with lower respiratory infection and receiving a chest radiograph for suspected CAP from 2013 to 2017. Clinicians reported the probability that the patient would develop severe complications of CAP (defined as respiratory failure, empyema or effusion, lung abscess or necrosis, metastatic infection, sepsis or septic shock, or death). The primary outcome was development of severe complications. RESULTS: Of 634 children, 37 (5.8%) developed severe complications. Of children developing severe complications after the ED visit, 62.1% were predicted as having 90% at the 90% at the 10% risk threshold. Gestalt performance was poor in the low-intermediate predicted risk category (1%–10%). Clinicians had only fair ability to discriminate children developing complications from those who did not (area under the receiver operator characteristic curve 0.747), with worse performance from less experienced clinicians (area under the receiver operator characteristic curve 0.693). CONCLUSIONS: Clinicians have only fair ability to discriminate children with CAP who develop severe complications from those who do not. Clinician gestalt performs best at very low or higher predicted risk thresholds, yet many children fall in the low-moderate predicted risk range in which clinician gestalt is limited. Evidence-based prognostic tools likely can improve on clinician gestalt, particularly when risk is low-moderate.