User-Centered Design and Implementation of an Interoperable FHIR Application for Pediatric Pneumonia Prognostication in a Randomized Trial.

OBJECTIVE: To support a pragmatic, electronic health record (EHR)-based randomized controlled trial, we applied user-centered design (UCD) principles, evidence-based risk communication strategies, and interoperable software architecture to design, test, and deploy a prognostic tool for children in emergency departments (EDs) with pneumonia. METHODS: Risk for severe in-hospital outcomes was estimated using a validated ordinal logistic regression model to classify pneumonia severity. To render the results usable for ED clinicians, we created an integrated SMART on FHIR web application built for interoperable use in two pediatric EDs using different EHR vendors: Epic and Cerner. We followed a UCD framework, including problem analysis and user research, conceptual design and early prototyping, user interface development, formative evaluation, and post-deployment summative evaluation. RESULTS: Problem analysis and user research from 39 clinicians and nurses revealed user preferences for risk aversion, accessibility, and timing of risk communication. Early prototyping and iterative design incorporated evidence-based design principles, including numeracy, risk framing, and best-practice visualization techniques. After rigorous unit and end-to-end testing, the application was successfully deployed in both EDs, which facilitatd enrollment, randomization, model visualization, data capture, and reporting for trial purposes. CONCLUSIONS: The successful implementation of a custom application for pneumonia prognosis and clinical trial support in two health systems on different EHRs demonstrates the importance of UCD, adherence to modern clinical data standards, and rigorous testing. Key lessons included the need for understanding users' real-world needs, regular knowledge management, application maintenance, and the recognition that FHIR applications require careful configuration for interoperability.

Yield of abdominal radiographs in children with suspected intussusception; rate of pneumoperitoneum and other abdominal pathology.

OBJECTIVES: Ultrasound is the criterion standard imaging modality for the diagnosis of intussusception. However, to our knowledge the utility of abdominal radiographs to concurrently screen for pneumoperitoneum or other abdominal pathology that could have a similar presentation has not been studied. Our institutional protocol requires the performance of AP supine and left lateral decubitus views of the abdomen prior to ultrasound evaluation for intussusception, providing an opportunity to examine the yield of abdominal radiographs in this setting. Our primary objective was to determine the rate of pneumoperitoneum on screening abdominal radiographs in children undergoing evaluation for intussusception. Our secondary objective was to determine the rate that other clinically significant pathology is found on these screening abdominal radiographs. METHODS: We performed a retrospective chart review of all patients under 6 years of age who had any imaging ordered in our large urban pediatric emergency department to evaluate for suspected intussusception during the calendar years 2018-2020. RESULTS: 1115 patient encounters met our inclusion criteria. Among 1090 who had screening abdominal radiographs, 82 (8%) had findings concerning for intussusception. Of those not concerning for intussusception, 635 (58%) were read as normal, 263 (24%) showed moderate to large stool burden, 107 (10%) showed generalized bowel distention, and 22 (2%) showed abnormal gastric distention. Individually the remainder of all other findings compromised <1% of encounters and included radiopaque foreign body (8), intraabdominal calcification (4), pneumonia/effusion (3), pneumatosis intestinalis, abdominal mass (2), diaphragmatic hernia (1), rib fracture (1), appendicolith (1), feeding tube malposition (1), and bowel wall thickening (1). In one encounter the patient had a bowel perforation with pneumoperitoneum present secondary to ingestion of multiple magnets. CONCLUSIONS: Our study indicates that radiograph-detected pneumoperitoneum is rare in children with suspected intussusception. Constipation is the most common abnormal finding on screening radiographs. Other findings occur in approximately 15% of total cases, some of which require further workup.

Validation of Childhood Pneumonia Prognostic Models for Use in Emergency Care Settings.

BACKGROUND: Unwarranted variation in disposition decisions exist among children with pneumonia. We validated three prognostic models for predicting pneumonia severity among children in the emergency department (ED) and hospital. METHODS: We performed a two-center, prospective study of children 6 months to <18 years presenting to the ED with pneumonia from January 2014 to May 2019. We evaluated three previously developed disease-specific prognostic models which use demographic, clinical, and diagnostic predictor variables, with each model estimating risk for Very Severe (mechanical ventilation or shock), Severe (ICU without very severe features), and Moderate/Mild (Hospitalization without severe features or ED discharge) pneumonia. Predictive accuracy was measured using discrimination (concordance or c-statistic) and re-calibration. RESULTS: There were 1088 children included in one or more of the three models. Median age was 3.6 years and the majority of children were male (53.7%) and identified as non-Hispanic White (63.7%). The distribution for the ordinal severity outcome was mild or moderate (79.1%), severe (15.9%), and very severe (4.9%). The three models each demonstrated excellent discrimination (C-statistic range across models [0.786-0.803]) with no appreciable degradation in predictive accuracy from the derivation cohort. CONCLUSIONS: All three prognostic models accurately identified risk for three clinically meaningful levels of pneumonia severity and demonstrated very good predictive performance. Physiologic variables contributed the most to model prediction. Application of these objective tools may help standardize and improve disposition and other management decisions for children with pneumonia.

Antibiotic clinical decision support for pneumonia in the ED: A randomized trial.

BACKGROUND: Electronic health record-based clinical decision support (CDS) is a promising antibiotic stewardship strategy. Few studies have evaluated the effectiveness of antibiotic CDS in the pediatric emergency department (ED). OBJECTIVE: To compare the effectiveness of antibiotic CDS vs. usual care for promoting guideline-concordant antibiotic prescribing for pneumonia in the pediatric ED. DESIGN: Pragmatic randomized clinical trial. SETTING AND PARTICIPANTS: Encounters for children (6 months-18 years) with pneumonia presenting to two tertiary care children s hospital EDs in the United States. INTERVENTION: CDS or usual care was randomly assigned during 4-week periods within each site. The CDS intervention provided antibiotic recommendations tailored to each encounter and in accordance with national guidelines. MAIN OUTCOME AND MEASURES: The primary outcome was exclusive guideline-concordant antibiotic prescribing within the first 24 h of care. Safety outcomes included time to first antibiotic order, encounter length of stay, delayed intensive care, and 3- and 7-day revisits. RESULTS: 1027 encounters were included, encompassing 478 randomized to usual care and 549 to CDS. Exclusive guideline-concordant prescribing did not differ at 24 h (CDS, 51.7% vs. usual care, 53.3%; odds ratio [OR] 0.94 [95% confidence interval [CI]: 0.73, 1.20]). In pre-specified stratified analyses, CDS was associated with guideline-concordant prescribing among encounters discharged from the ED (74.9% vs. 66.0%; OR 1.53 [95% CI: 1.01, 2.33]), but not among hospitalized encounters. Mean time to first antibiotic was shorter in the CDS group (3.0 vs 3.4 h; p = .024). There were no differences in safety outcomes. CONCLUSIONS: Effectiveness of ED-based antibiotic CDS was greatest among those discharged from the ED. Longitudinal interventions designed to target both ED and inpatient clinicians and to address common implementation challenges may enhance the effectiveness of CDS as a stewardship tool.

Serious infections are rare in well-appearing neonates with hypothermia identified incidentally at routine visits.

OBJECTIVES: It is not established whether diagnostic testing and antimicrobial treatment are warranted in well-appearing neonates without other signs or symptoms who have hypothermia identified incidentally at a routine visit with their primary care provider. METHODS: This was a retrospective observational study of well-appearing neonates who were noted at a routine visit to be hypothermic (<97.7°F or <36.5°C) and referred to a pediatric emergency department over an 8.5-year period. Excluded were those transferred from an outside hospital and those with signs of illness, including apnea, bradycardia, fever, hypoglycemia, ill appearance, lethargy, poor feeding, respiratory distress, tachycardia, or vomiting. Patient characteristics, laboratory results, antimicrobial treatment, and clinical outcomes were recorded. RESULTS: Among a final cohort of 212 neonates with incidental hypothermia, no urine (n = 195) or blood (n = 198) culture grew a bacterial pathogen. No CSF culture (n = 168) grew a bacterial pathogen and no CSF PCR test (n = 142) was positive for herpes simplex virus. Contaminants were isolated in 3 urine and 3 blood cultures. CONCLUSION: Well-appearing neonates with incidentally noted hypothermia at a routine visit are at low risk for serious infection and may not warrant a full sepsis evaluation.

Associations between comorbidity-related functional limitations and pneumonia outcomes.

BACKGROUND: Underlying comorbidities are common in children with pneumonia. OBJECTIVE: To determine associations between comorbidity-related functional limitations and risk for severe pneumonia outcomes. DESIGN, SETTING, AND PARTICIPANTS: We prospectively enrolled children <18 years with and without comorbidities presenting to the emergency department with clinical and radiographic pneumonia at two institutions. Comorbidities included chronic conditions requiring daily medications, frequent healthcare visits, or which limited age-appropriate activities. Among children with comorbidities, functional limitations were defined as none or mild, moderate, and severe. MAIN OUTCOMES AND MEASURES: Outcomes included an ordinal severity outcome, categorized as very severe (mechanical ventilation, shock, or death), severe (intensive care without very severe features), moderate (hospitalization without severe features), or mild (discharged home), and length of stay (LOS). Multivariable ordinal logistic regression was used to examine associations between comorbidity-related functional limitations and outcomes, while accounting for relevant covariates. RESULTS: A cohort of 1116 children, including 452 (40.5%) with comorbidities; 200 (44.2%) had none or mild functional limitations, 93 (20.6%) moderate, and 159 (35.2%) had severe limitations. In multivariable analysis, comorbidity-related functional limitations were associated with the ordinal severity outcome and LOS (p < .001 for both). Children with severe functional limitations had tripling of the odds of a more severe ordinal (adjusted odds ratio [aOR]: 3.01, 95% confidence interval [2.05, 4.43]) and quadrupling of the odds for longer LOS (aOR: 4.72 [3.33, 6.70]) as compared to children without comorbidities. CONCLUSION: Comorbidity-related functional limitations are important predictors of disease outcomes in children with pneumonia. Consideration of functional limitations, rather than the presence of comorbidity alone, is critical when assessing risk of severe outcomes.

Reliability of the Behaviorally Anchored Rating Scale (BARS) for assessing non-technical skills of medical students in simulated scenarios.

PURPOSE: Caring for critically ill patients requires non-technical skills such as teamwork, communication, and task management. The Behaviorally Anchored Rating Scale (BARS) is a brief tool used to assess non-technical skills. The investigators determined inter- and intra-rater reliability of the BARS when used to assess medical students in simulated scenarios. METHOD: The investigators created simulation scenarios for medical students during their pediatric clerkship. Content experts reviewed video recordings of the simulations and assigned BARS scores for four performance components (Situational Awareness, Decision-Making, Communication, and Teamwork) for the leader and for the team as a whole. Krippendorff's alpha with ordinal difference was calculated to measure inter- and intra-rater reliability. RESULTS: Thirty medical students had recordings available for review. Inter- and intra-rater reliability for performance components were, respectively, Individual Situational Awareness (0.488, 0.638), Individual Decision-Making (0.529, 0.691), Individual Communication (0.347, 0.473), Individual Teamwork (0.414, 0.466), Team Situational Awareness (0.450, 0.593), Team Decision Making (0.423, 0.703), Team Communication (0.256, 0.517), and Team Teamwork (0.415, 0.490). CONCLUSIONS: The BARS demonstrated limited reliability when assessing medical students during their pediatric clerkship. Given the unique needs of this population, a modified or new objective scoring system for assessing non-technical skills may be needed for medical students.

Association Between Procalcitonin and Antibiotics in Children With Community-Acquired Pneumonia.

OBJECTIVE: To determine whether empirical antibiotic initiation and selection for children with pneumonia was associated with procalcitonin (PCT) levels when results were blinded to clinicians. METHODS: We enrolled children <18 years with radiographically confirmed pneumonia at 2 children's hospitals from 2014 to 2019. Blood for PCT was collected at enrollment (blinded to clinicians). We modeled associations between PCT and (1) antibiotic initiation and (2) antibiotic selection (narrow versus broad-spectrum) using multivariable logistic regression models. To quantify potential stewardship opportunities, we calculated proportions of noncritically ill children receiving antibiotics who also had a low likelihood of bacterial etiology (PCT <0.25 ng/mL) and those receiving broad-spectrum therapy, regardless of PCT level. RESULTS: We enrolled 488 children (median PCT, 0.37 ng/mL; interquartile range [IQR], 0.11-2.38); 85 (17%) received no antibiotics (median PCT, 0.32; IQR, 0.09-1.33). Among the 403 children receiving antibiotics, 95 (24%) received narrow-spectrum therapy (median PCT, 0.24; IQR, 0.08-2.52) and 308 (76%) received broad-spectrum (median PCT, 0.46; IQR, 0.12-2.83). In adjusted analyses, PCT values were not associated with antibiotic initiation (odds ratio [OR], 1.02, 95% confidence interval [CI], 0.97%-1.06%) or empirical antibiotic selection (OR 1.07; 95% CI, 0.97%-1.17%). Of those with noncritical illness, 246 (69%) were identified as potential targets for antibiotic stewardship interventions. CONCLUSION: Neither antibiotic initiation nor empirical antibiotic selection were associated with PCT values. Whereas other factors may inform antibiotic treatment decisions, the observed discordance between objective likelihood of bacterial etiology and antibiotic use suggests important opportunities for stewardship.

Multi-analyte calibration and verification of a multi-parameter laser-based pulse oximeter.

Almost since its introduction pulse oximetry was known to overestimate oxygen saturation in cases of carbon monoxide poisoning or elevated methemoglobin (metHb) levels. To eliminate this dangerous behavior some manufacturers have added additional LED emitters to try to increase the number of measured hemoglobin species and to improve measurement accuracy, but have not been very successful. We hypothesized that the use of narrow-band laser light sources would make accurate and precise measurement of the four primary species of hemoglobin possible, even in cases of elevated levels of carboxyhemoglobin (COHb). Calibration and verification studies were performed on a tissue simulator that employed an artificial finger pulsating with whole human blood. This simulator allowed safe generation of 165 different combinations of the levels of oxyhemoglobin (O2Hb), COHb, metHb, and reduced hemoglobin (RHb) for calibration of the laser-based pulse oximeter. A follow-on study used 56 mixed hemoglobin levels for verification and statistical analysis of the performance of this device. This laser-based pulse oximeter measured all four species of hemoglobin accurately and precisely (ARMS ≤ 1.8%) for metHb levels in the clinically normal range. At elevated metHb levels the device continued to provide accurate and precise measurements of metHb and RHb (ARMS ≤ 1.7%). The use of monochromatic laser light sources can create a new generation of highly accurate, multi-parameter, pulse oximeters.

Evaluating Discrepancies in Percent Total Body Surface Area Burn Assessments Between Prehospital Providers and Burn Center Physicians.

Burns are routinely assessed at the scene of the incident by prehospital or emergency medical services providers. The initial management of burns is based on the calculation of the extent of the injury, reported as percent total body surface area (TBSA). This study evaluates discrepancies in the estimation of TBSA between prehospital providers and burn team physicians over a 3-year period at an academic, university medical center serving as the regional burn center. A total of 120 adult and 27 pediatric patients (younger than age 16 years) were included in this study; 95 (65%) patients were male, 67 (46%) patients were Caucasian, 62 (42%) patients had no healthcare insurance, and the median age was 35 years (interquartile range [IQR] 27). The most common etiology of burns was hot liquid, 39 (26.5%). Median [IQR] and mean (SD) estimated TBSA (%) were 4 [1-10] and 8.6 (12.8) for prehospital providers and 2 [1-6] and 5.9 (9.9) for burn team physicians. Bland-Altman plots evaluating second- and third-degree burns separately and combined demonstrated that, as burns involved more surface area, agreement decreased between emergency medical service providers and burn physicians. Agreement between prehospital providers and burn physicians decreased as TBSA of burns increased. This finding reaffirms the need for more standardized education and training for all medical personnel.

Prospective Observational Study of Clinical Outcomes After Intravenous Magnesium for Moderate and Severe Acute Asthma Exacerbations in Children.

BACKGROUND: There is limited knowledge regarding whether intravenous magnesium (IV-Mg) improves outcomes in children with acute asthma exacerbations. OBJECTIVE: To examine whether IV-Mg improves outcomes in children with moderate and severe exacerbations. METHODS: We performed a secondary analysis using data from a prospective observational cohort of children aged 5 to 17 years with moderate and severe exacerbations. Standardized treatment included systemic corticosteroid and inhaled albuterol, with consideration of IV-Mg (75 mg/kg) for patients with insufficient response after 20 minutes. Propensity score (PS) models were used to examine associations of IV-Mg treatment with change in the validated Acute Asthma Intensity Research Score, hospitalization rate, and time to spacing of inhaled albuterol of 4 hours or more among hospitalized participants. RESULTS: Among 301 children, median (interquartile range) age was 8.1 (6.4-10.2) years, 170 were Black (57%), 201 were male (67%), and 84 received IV-Mg (28%). In a PS covariate-adjusted multivariable linear regression model, IV-Mg treatment was associated with a 2-hour increase in the Acute Asthma Intensity Research Score (ß-coefficient = 0.98; 95% confidence interval [CI], 0.20-1.77), indicating increased exacerbation severity. Three additional PS-based models yielded similar results. Participants receiving IV-Mg had 5.8-fold (95% CI, 2.8-11.9) and 6.8-fold (95% CI, 3.6-12.9) greater odds of hospitalization in PS-based multivariable regression models. Among hospitalized participants, there was no difference in time to albuterol of every 4 hours or more in a PS covariate-adjusted Cox proportional hazards model (hazard ratio = 1.2; 95% CI, 0.8-1.8). CONCLUSIONS: Among children with moderate and severe exacerbations, IV-Mg is associated with increased exacerbation severity, increased risk for hospitalization, and no acceleration in exacerbation resolution among hospitalized participants.

Nebulized albuterol delivery is associated with decreased skeletal muscle strength in comparison with metered-dose inhaler delivery among children with acute asthma exacerbations.

OBJECTIVE: Albuterol is a ß2-agonist and causes an intracellular shift of potassium from the interstitium. Whole-body hypokalemia is known to cause skeletal muscle weakness, but whether this occurs as a result of hypokalemia from the intracellular shift during albuterol treatment is unknown. We sought to determine if albuterol total dose or route of administration (nebulization and/or metered-dose inhaler) is associated with skeletal muscle weakness. METHODS: This was a prospective observational study using convenience sampling. Skeletal muscle strength was measured before and after 1 hour of albuterol treatment using a hand-grip dynamometer in participants aged 5-17 years with acute asthma exacerbation in the emergency department. We examined associations of albuterol dose and route of administration with changes in grip strength. RESULTS: Among 50 participants, 10 received continuous albuterol by nebulizer and 40 received albuterol by metered-dose inhaler. The median (interquartile range) in change of grip was -7.8% (interquartile range, -23.3, +5.1) for those treated with a nebulizer and +2.4% (interquartile range, -5%, +12.7%) for those treated with a metered-dose inhaler (P = 0.036 for the difference). In a multiple linear regression model adjusted for the pretreatment Acute Asthma Intensity Research Score and age, participants treated with a nebulizer had a 12.9% decrease in skeletal muscle strength compared with those treated with a metered-dose inhaler. CONCLUSION: Higher doses of albuterol administered via nebulization result in decreased skeletal muscle strength in patients with acute asthma; whereas, albuterol administration via metered-dose inhalers showed no effect on skeletal muscle strength.

Pneumonia Severity in Children: Utility of Procalcitonin in Risk Stratification.

OBJECTIVES: To determine if serum procalcitonin, an indicator of bacterial etiology in pneumonia in all ages and a predictor of severe pneumonia in adults, is associated with disease severity in children with community-acquired pneumonia. METHODS: We prospectively enrolled children 2 months to <18 years with clinical and radiographic pneumonia at 2 children's hospitals (2014-2019). Procalcitonin samples were obtained at presentation. An ordinal outcome scale of pneumonia severity was defined: very severe (intubation, shock, or death), severe (intensive care admission without very severe features and/or high-flow nasal cannula), moderate (hospitalization without severe or very severe features), and mild (discharge). Hospital length of stay (LOS) was also examined. Ordinal logistic regression was used to model associations between procalcitonin and outcomes. We estimated adjusted odds ratios (aORs) for a variety of cut points of procalcitonin ranging from 0.25 to 3.5 ng/mL. RESULTS: The study included 488 children with pneumonia; 30 (6%) were classified as very severe, 106 (22%) as severe, 327 (67%) as moderate, and 25 (5%) as mild. Median procalcitonin in the very severe group was 5.06 (interquartile range [IQR] 0.90-16.83), 0.38 (IQR 0.11-2.11) in the severe group, 0.29 (IQR 0.09-1.90) in the moderate group, and 0.21 (IQR 0.12-1.2) in the mild group. Increasing procalcitonin was associated with increasing severity (range of aORs: 1.03-1.25) and increased LOS (range of aORs: 1.04-1.36). All comparisons were statistically significant. CONCLUSIONS: Higher procalcitonin was associated with increased severity and LOS. Procalcitonin may be useful in helping clinicians evaluate pneumonia severity.

Pilot Study of Peak Plasma Concentration After High-Dose Oral Montelukast in Children With Acute Asthma Exacerbations.

Acute asthma exacerbations are primarily due to airway inflammation and remain one of the most frequent reasons for childhood hospitalizations. Although systemic corticosteroids remain the mainstay of therapy because of their anti-inflammatory properties, not all inflammatory pathways are responsive to systemic corticosteroids, necessitating hospital admission for further management. Cysteinyl leukotrienes (LTs) are proinflammatory mediators that play an important role in systemic corticosteroids non-responsiveness. Montelukast is a potent LT-receptor antagonist, and an intravenous preparation caused rapid, sustained improvement of acute asthma exacerbations in adults. We hypothesized that a 30-mg dose of oral montelukast achieves peak plasma concentrations (Cmax ), comparable to the intravenous preparation (1700 ng/mL) and would be well tolerated in 15 children aged 5 to 12 years with acute asthma exacerbations. After administration of montelukast chewable tablets, blood samples were collected at 0, 15, 30, 45, 60, 120, 180, and 240 minutes. Plasma was separated and frozen at -80°C until analysis for montelukast concentration using liquid chromatography- tandem mass spectrometry. Median time to Cmax (tmax ) was 3.0 hours. Six participants (40%) achieved Cmax of 1700 ng/mL or higher. However, there was high interindividual variability in peak plasma concentration (median Cmax of 1378 ng/mL; range, 16-4895 ng/mL). No participant had side effects or adverse events. Plasma concentrations from this pilot study support the design of a weight-based dose-finding study aimed at selecting an optimal dose for future clinical trials to assess the efficacy of high-dose oral montelukast in children with moderate to severe asthma exacerbations.

Natural Language Processing and Machine Learning to Enable Clinical Decision Support for Treatment of Pediatric Pneumonia.

Pneumonia is the most frequent cause of infectious disease-related deaths in children worldwide. Clinical decision support (CDS) applications can guide appropriate treatment, but the system must first recognize the appropriate diagnosis. To enable CDS for pediatric pneumonia, we developed an algorithm integrating natural language processing (NLP) and random forest classifiers to identify potential pediatric pneumonia from radiology reports. We deployed the algorithm in the EHR of a large children's hospital using real-time NLP. We describe the development and deployment of the algorithm, and evaluate our approach using 9-months of data gathered while the system was in use. Our model, trained on individual radiology reports, had an AUC of 0.954. The intervention, evaluated on patient encounters that could include multiple radiology reports, achieved a sensitivity, specificity, and positive predictive value of0.899, 0.949, and 0.781, respectively.