Pediatric Lyme disease: systematic assessment of post-treatment symptoms and quality of life.

BACKGROUND: Lyme disease is common among children and adolescents. Antibiotic treatment is effective, yet some patients report persistent symptoms following treatment, with or without functional impairment. This study characterized long-term outcome of pediatric patients with Lyme disease and evaluated the case definition of post-treatment Lyme disease (PTLD) syndrome. METHODS: The sample included 102 children with confirmed Lyme disease diagnosed 6 months-10 years prior to enrollment (M = 2.0 years). Lyme diagnosis and treatment information was extracted from the electronic health record; parent report identified presence, duration, and impact of symptoms after treatment. Participants completed validated questionnaires assessing health-related quality of life, physical mobility, fatigue, pain, and cognitive impact. RESULTS: Most parents reported their child's symptoms resolved completely, although time to full resolution varied. Twenty-two parents (22%) indicated their child had at least one persistent symptom >6 months post-treatment, 13 without functional impairment (PTLD symptoms) and 9 with functional impairment (PTLD syndrome). Children with PTLD syndrome had lower parent-reported Physical Summary scores and greater likelihood of elevated fatigue. CONCLUSIONS: In the current study, most children with Lyme disease experienced full resolution of symptoms, including those who initially met PTLD syndrome criteria. Effective communication about recovery rates and common symptoms that may persist post-treatment is needed. IMPACT: The majority of pediatric patients treated for all stages of Lyme disease reported full resolution of symptoms within 6 months. 22% of pediatric patients reported one or more symptom persisting >6 months, 9% with and 13% without accompanying functional impairment. Effective communication with families about recovery rates and common symptoms that may persist post-treatment of Lyme disease is needed.

Assessing the Effect of Augmented Reality on Procedural Outcomes During Ultrasound-Guided Vascular Access.

OBJECTIVE: Augmented reality devices are increasingly accepted in health care, though most applications involve education and pre-operative planning. A novel augmented reality ultrasound application, HoloUS, was developed for the Microsoft HoloLens 2 to project real-time ultrasound images directly into the user's field of view. In this work, we assessed the effect of using HoloUS on vascular access procedural outcomes. METHODS: A single-center user study was completed with participants with (N = 22) and without (N = 12) experience performing ultrasound-guided vascular access. Users completed a venipuncture and aspiration task a total of four times: three times on study day 1, and once on study day 2 between 2 and 4 weeks later. Users were randomized to use conventional ultrasound during either their first or second task and the HoloUS application at all other times. Task completion time, numbers of needle re-directions, head adjustments and needle visualization rates were recorded. RESULTS: For expert users, task completion time was significantly faster using HoloUS (11.5 s, interquartile range [IQR] = 6.5-23.5 s vs. 18.5 s, IQR = 11.0-36.5 s; p = 0.04). The number of head adjustments was significantly lower using the HoloUS app (1.0, IQR = 0.0-1.0 vs. 3.0, IQR = 1.0-5.0; p < 0.0001). No significant differences were identified in other measured outcomes. CONCLUSION: This is the first investigation of augmented reality-based ultrasound-guided vascular access using the second-generation HoloLens. It demonstrates equivalent procedural efficiency and accuracy, with favorable usability, ergonomics and user independence when compared with traditional ultrasound techniques.

Cardiac evaluation of hospitalized children with 2019 coronavirus (COVID-19) infection at a single large quaternary center.

Background: Cardiac complications of serious SARS-CoV-2 infections, especially Multisystem Inflammatory Syndrome of Children (MIS-C) are well described, however current studies have not considered pediatric patients hospitalized with no cardiac concerns. We established a protocol for cardiac evaluation of all admitted COVID-19 patients three weeks post-discharge, irrespective of cardiac concerns. We assessed cardiovascular outcomes and hypothesized that patients with absent cardiac concerns are at lower risk for cardiac abnormalities. Methods: This was a retrospective study of 160 patients admitted for COVID-19 (excluding MIS-C) between March 2020 and September 2021 with subsequent echocardiogram(s) performed at our center. Patients were divided into 4 subgroups: Group 1 included patients with absent cardiac concerns, admitted to acute care (1a) and intensive care unit (ICU) (1 b). Group 2 included patients with cardiac concerns, admitted to acute care (2a) and ICU (2 b). Groups were compared based on clinical endpoints and echocardiographic measurements, including tissue Doppler imaging (TDI) assessment of diastolic function (z-score of septal Mitral E/TDI E' and lateral E/TDI E'). Chi-squared, Fisher's exact, and Kruskal-Wallis tests were used. Results: Traditional cardiac abnormalities varied significantly between the groups; with Group 2 b having the most (n = 8, 21%), but still found in Group 1a (n = 2, 3%) and Group 1 b (n = 1, 5%). No patients in Group 1 demonstrated abnormal systolic function, compared to Group 2a (n = 1, 3%) and Group 2 b (n = 3, 9%, p = 0.07). When including TDI assessment of diastolic function, the total incidence of abnormalities found on echocardiogram was increased in all groups. Conclusion: Cardiac abnormalities were found in pediatric patients admitted with COVID-19, even those without apparent cardiovascular concerns. The risk was greatest in ICU-admitted patients with cardiac concerns. The clinical significance of diastolic function assessment in these patients remains unknown. Further studies are needed to assess long-term cardiovascular sequelae of children with COVID-19, irrespective of cardiac concerns.

Assessing trainee critical thinking skills using a novel interactive online learning tool.

BACKGROUND: Critical thinking is essential for the accurate diagnosis and management of patients. It is correlated with academic success. OBJECTIVE: Our objective was to design a novel tool for interactive online learning to improve knowledge and to assess trainees' critical thinking skills using the framework of the American Philosophical Association (APA). METHODS: Residents, fellows and students participated in an online, self-directed case-based vignette activity to learn malaria diagnosis and management. Pre and post-tests with multiple choice and open-ended case-based questions assessed knowledge and critical thinking. Comparison between pre and post-test scores across subgroups were performed using paired t-tests or one-way ANOVA. RESULTS: Between 4 April 2017 to 14 July 2019, 62 of 75 (82%) eligible subjects completed both the pre and the post-test. Improved post-test scores occurred in 90% of medical students, p=0.001, 77% of residents, p<0.001, 60% of fellows, p=0.72 and 75% of trainees overall, p=<0.001. Fellows had higher pre-test scores than students or residents but there was no difference by level of training on the post-test. CONCLUSIONS: This interactive online learning activity effectively imparted medical knowledge and improved trainee responses to questions requiring critical thinking. To our knowledge, this is the first time the APA's critical thinking framework has been incorporated into interactive online learning and assessment of critical thinking skills in medical trainees. We applied this innovation specifically in global health education, but there is obvious potential to expand it to a wide variety of areas of clinical training.

Interprofessional Extracorporeal Membrane Oxygenation Cardiopulmonary Resuscitation Simulations Aimed at Decreasing Actual Cannulation Times: A Longitudinal Study.

BACKGROUND: Since 2013, the cardiac intensive care unit (CICU) at Children's National has conducted annual extracorporeal membrane oxygenation cardiopulmonary resuscitation (ECPR) simulations that focus on team dynamics, room setup, and high-quality CPR. In 2019 and 2020, the simulations were expanded to include the surgical and extracorporeal membrane oxygenation (ECMO) teams in an effort to better understand and improve this process. METHODS: During a 4-week period in 2019, 7 peripheral ECPR simulations were conducted, and through a 3-week period in 2020, 7 central ECPR simulations were conducted. Participants in each session included: 8 to 10 CICU nurses, 1 CICU attending, 1 to 2 ICU or cardiology fellows, 1 cardiovascular surgery fellow or attending, and 1 ECMO specialist. For each session, the scenario continued until the simulated patient was on full cardiopulmonary bypass. An ECMO trainer was used for peripheral simulations and a 3-dimensionally-printed heart was used for central cannulations. An ECMO checklist was used to objectively determine when the patient and room were fully prepared for surgical intervention, and simulated cannulation times were recorded for both groups. A retrospective chart review was conducted to compare actual cannulation times before and after the intervention period, and video was used to review the events and assist in dividing them into medical versus surgical phases. Control charts were used to trend the total ECPR times before and after the intervention period, and mean and P values were calculated for both ECPR times and for all other categorical data. RESULTS: Mean peripheral ECPR times decreased significantly from 71.7 to 45.1 minutes ( P = 0.036) after the intervention period, and this was reflected by a centerline shift. Although we could not describe a similar decrease in central ECPR times because there were only 6 postintervention events, the times for each of these events were shorter than the historical mean of 37.8 minutes. There was a trend in improved survival, which did not meet significance both among patients undergoing peripheral ECPR (15.4% ± 10% to 43.8% ± 12.4%, P = 0.10) and central ECPR (36.4% ± 8.4% to 50% ± 25%, P = 0.60). The percentage of time dedicated to the medical phases of the actual versus simulated procedures was very consistent among both peripheral (33.0% vs. 31.9%) and central (39.6% vs. 39.8%) cannulations. CONCLUSIONS: We observed a significant decrease in peripheral cannulation times at our institution after conducting interprofessional ECPR simulations taken to the establishment of full cardiopulmonary bypass. The use of an ECMO trainer and a 3-dimensionally-printed heart allowed for both the medical and surgical phases of the procedure to be studied in detail, providing opportunities to streamline and improve this complex process. Larger multisite studies will be needed in the future to assess the effect of efforts like these on patient survival.

An educational intervention to facilitate appropriate subspecialty referrals: a study assessing resident communication skills.

BACKGROUND: Our goal was to improve pediatric residents' advanced communication skills in the setting of referral to address the entrustable professional activity of subspecialty referral identified by the American Board of Pediatrics. To accomplish this aim, we created a referral and consultation curriculum to teach and assess core communication skills in subspecialty referral involving an adolescent with syncope, an anxiety-provoking symptom that is rarely associated with serious pathology. METHODS: We utilized blended multimodal educational interventions to improve resident communication skills in referral of patients. Trainees participated in 1) an interactive online module on syncope focusing on "red-flag" symptoms that would warrant a subspecialty cardiology referral and 2) a 4-h intervention with Standardized Parents (SPs), focusing on the case-based application of communication skills. Communication skills were assessed by two pre- and post- Objective Structured Clinical Examination encounters of patients with syncope, with an SP evaluation using a 20-item checklist. Analysis was performed with Sign test and McNemar's test. Trainees provided feedback on a Critical Incident Questionnaire, which was analyzed qualitatively. RESULTS: Sixty-four residents participated. There was an overall improvement in communication skills based on SP scores (82.7 ± 10.9% to 91.7 ± 5.0%, p < 0.001), and 13/20 items demonstrated significant improvement post-intervention. Residents' improved performance enabled them to address patient/family emotions, explain referral logistics, and clarify concerns to agree on a plan. CONCLUSIONS: By participating in this curriculum, residents' communication skills improved immediately post-intervention. Further research is needed to assess if this intervention improves patient care by providing residents with enduring skills to judiciously manage the referral process.

Pediatric Mortality and Acute Kidney Injury Are Associated with Chloride Abnormalities in Intensive Care Units in the United States: A Multicenter Observational Study.

Our objective was to determine in children in the intensive care unit (ICU) the incidence of hyperchloremia (>110 mmol/L) and hypochloremia (<98 mmol/L), the association of diagnoses with chloride abnormalities, and the associations of mortality and acute kidney injury (AKI) with chloride abnormalities. We analyzed the initial, maximum, and minimum chloride measurements of 14,684 children in the ICU with ≥1 chloride measurement in the Health Facts database between 2009 and 2016. For hyperchloremia and hypochloremia compared with normochloremia, mortality rates increased three to fivefold and AKI rates increased 1.5 to threefold. The highest mortality rate (7.7%; n = 95/1,234) occurred with hyperchloremia in the minimum chloride measurement group and the highest AKI rate (7.7%; n = 72/930) occurred with hypochloremia in the initial chloride measurement group. The most common diagnostic categories associated with chloride abnormalities were injury and poisoning; respiratory; central nervous system; infectious and parasitic diseases; and endocrine, nutritional, metabolic, and immunity disorders. Controlled for race, gender, age, and diagnostic categories, mortality odds ratios, and AKI odds ratios were significantly higher for hyperchloremia and hypochloremia compared with normochloremia. In conclusion, hyperchloremia and hypochloremia are independently associated with mortality and AKI in children in the ICU.

National Intravenous Acetaminophen Use in Pediatric Inpatients From 2011-2016.

OBJECTIVE: To 1) determine current intravenous (IV) acetaminophen use in pediatric inpatients; and 2) determine the association between opioid medication duration when used with or without IV acetaminophen. METHODS: A retrospective analysis of pediatric inpatients exposed to IV acetaminophen from January 2011 to June 2016, using the national database Health Facts. RESULTS: Eighteen thousand one hundred ninety-seven (2.0%) of 893,293 pediatric inpatients received IV acetaminophen for a median of 14 doses per patient (IQR, 8-56). A greater proportion of IV acetaminophen patients were admitted to the intensive care unit (ICU) (14.8% vs 5.1%, p < 0.0001), received positive pressure ventilation (2.0% vs 1.5%, p < 0.0001), had a higher hospital mortality rate (0.9% vs 0.3%, p < 0.0001), and were operative (35.5% vs 12.8%, p < 0.001) than those not receiving IV acetaminophen. The most common operations associated with IV acetaminophen use were musculoskeletal and digestive system operations. Prescription of IV acetaminophen increased over time, both in prescription rates and number of per patient doses. Of the 18,197 patients prescribed IV acetaminophen, 16,241 (89.2%) also were prescribed opioids during their hospitalization. A multivariate analysis revealed patients prescribed both IV acetaminophen and opioids had a 54.8% increase in opioid duration as compared with patients who received opioids alone. CONCLUSIONS: This is the first study to assess IV acetaminophen prescription practices for pediatric inpatients. Intravenous acetaminophen prescription was greater in the non-operative pediatric inpatient population than operative patients. Intravenous acetaminophen prescription was associated with an increase in opioid duration as compared with patients who received opioids alone, suggesting that it is commonly used to supplement opioids for pain relief.

Autoantibody cluster analysis in juvenile lupus nephritis.

OBJECTIVE: Demographics, clinical features, and biomarkers do not consistently anticipate risk of end-stage renal disease (ESRD) in juvenile lupus nephritis (LN). Here, the existence of autoantibody clusters predictive of ESRD was explored in a cohort of biopsy-proven juvenile LN. METHODS: A retrospective chart review was performed of patients with juvenile systemic lupus erythematosus (jSLE) and biopsy-confirmed LN. Primary endpoints were ESRD and mortality. Patients were included for K-medians cluster analysis if they had a complete autoantibody profile, which included ANA titer, anti-dsDNA, anti-Smith, anti-RNP, anti-Ro/SSA, anti-La/SSB. Chi-square test was used for categorical variables and one-way ANOVA for continuous measures. Significance was p<0.05. RESULTS: Fifty-three met inclusion criteria, of which 45 were female and 37 were black. Over 80% developed LN within one year of jSLE onset and more than half (n=29) had LN at diagnosis of jSLE. Six developed ESRD. No mortalities were reported. Forty-six had a complete autoantibody profile, including four with ESRD. Three clusters were identified. Group 1 (n=8) was defined by anti-dsDNA; group 2 (n=28) by high-titer ANA (>1:1280), anti-Smith, anti-RNP, and anti-Ro/SSA; and group 3 (n=10) by anti-dsDNA and anti-Ro/SSA. There was no difference between the groups in demographics, jSLE manifestations, or markers of renal function. One in group 2 and three in group 3 developed ESRD. Those in group 3 were younger at diagnosis of LN (p=0.084) and had the highest frequency of ESRD (p=0.025). CONCLUSION: Cluster analysis revealed the highest frequency of ESRD in the group with LN defined by anti-Ro/SSA and anti-dsDNA co-positivity. Key Points • Lupus nephritis commonly is present at diagnosis of juvenile systemic lupus erythematosus or develops within the first year. • End-stage renal disease was more frequent in the cluster defined by anti-dsDNA and anti-Ro/SSA co-positivity; patients with this profile may benefit from more aggressive immunosuppression.

Multinational Analysis of Children Transfused With Pathogen Inactivated Platelets.

BACKGROUND: Pathogen inactivated (PI) platelets are a technological advancement in blood safety; however, the pediatric experience is not well characterized. We studied pediatric patients who received transfusions of PI platelets across several centers and countries to determine if transfusion reaction rates differed when compared with conventional platelets. METHODS: This is a retrospective multisite study conducted during 2 time periods. The study period started at the time each site began using PI platelets on a widespread basis, and the control period was a similar timespan before PI introduction. Suspected acute transfusion reactions were compared. RESULTS: The study included 3839 pediatric patients who were 0 to 18 years of age who received >7930 platelet transfusions, in total, across 4 centers in 3 countries between 2013 and 2019. The age distribution of patients in the study and control period was not significantly different (P = .190). There was not a difference in the percentage of patients who had any type of transfusion reaction between the time periods (1.0% and 1.1%, P = .803). There were fewer patients with mild allergic reactions in the study period compared with the control period (0.2% and 0.7% of patients with reactions, respectively, P = .018). CONCLUSIONS: Pediatric patients have the same rate of acutely suspected transfusion reactions when receiving PI or conventional platelet transfusions. Subgroup analysis found fewer mild allergic reactions in the study period, which was contemporaneous to the addition of using platelet additive solution more broadly. Future studies of PI platelets should include children to better assess transfusion efficacy and hemostatic outcomes.

Cardiac echocardiogram findings of severe acute respiratory syndrome coronavirus-2-associated multi-system inflammatory syndrome in children.

BACKGROUND: A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic. OBJECTIVES: To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children. METHODS: Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher's exact, and Wilcoxon rank sum. RESULTS: Thirty-nine children with median (interquartile range) age 7.8 (3.6-12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26-61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04). CONCLUSION: Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

Comparison of First and Second Wave Cohorts of Multisystem Inflammatory Disease Syndrome IN Children.

Comparing first and second wave MIS-C cohorts at our quaternary pediatric institution, second wave were older, presented more frequently with shortness of breath, higher maximum troponin and N-terminal BNP, and more frequently required advanced respiratory and inotropic support. Despite increased severity in the second cohort, both cohorts had similar rates of coronary artery abnormalities, systolic dysfunction, and length of stay.

"Sick or not sick?" A mixed methods study evaluating the rapid determination of illness severity in a pediatric emergency department.

OBJECTIVES: Experienced physicians must rapidly identify ill pediatric patients. We evaluated the ability of an illness rating score (IRS) to predict admission to a pediatric hospital and explored the underlying clinical reasoning of the gestalt assessment of illness. METHODS: We used mixed-methods to study pediatric emergency medicine physicians at an academic children's hospital emergency department (ED). Physicians rated patients' illness severity with the IRS, anchored by 0 (totally well) and 10 (critically ill), and shared their rationale with concurrent think-aloud responses. The association between IRS and need for hospitalization, respiratory support, parenteral antibiotics, and resuscitative intravenous (IV) fluids were analyzed with mixed effects linear regression. Area under the curve (AUC) receiver operator characteristic (ROC) curve and test characteristics at different cut-points were calculated for IRS as a predictor of admission. Think-aloud responses were qualitatively analyzed via inductive process. RESULTS: A total of 141 IRS were analyzed (mean 3.56, SD 2.30, range 0-9). Mean IRS were significantly higher for patients requiring admission (4.32 vs. 3.13, p<0.001), respiratory support (6.15 vs. 3.98, p = 0.033), IV fluids (4.53 vs. 3.14, p < 0.001), and parenteral antibiotics (4.68 vs. 3.32, p = 0.009). AUC for IRS as a predictor of admission was 0.635 (95% CI: 0.534-0.737). Analysis of 95 think-aloud responses yielded eight categories that describe the underlying clinical reasoning. CONCLUSIONS: Rapid assessments as captured by the IRS differentiated pediatric patients who required admission and medical interventions. Think-aloud responses for the rationale for rapid assessments may form the basis for teaching the skill of identifying ill pediatric patients.

Association of Intravenous Acetaminophen Administration With the Duration of Intravenous Opioid Use Among Hospitalized Pediatric Patients.

Importance: Adoption of multimodal pain regimens that incorporate nonopioid analgesic medications to reduce inpatient opioid administration can prevent serious opioid-related adverse effects in children, including tolerance, withdrawal, delirium, and respiratory depression. Intravenous (IV) acetaminophen is in widespread pediatric use; however, its effectiveness as an opioid-sparing agent has not been evaluated in general pediatric inpatients. Objective: To determine if IV acetaminophen administered prior to IV opioids is associated with a reduction in the total duration of IV opioids administered compared with IV opioids administered without IV acetaminophen in general pediatric inpatients. Design, Setting, and Participants: This comparative effectiveness research study included data on pediatric inpatients from 274 US hospitals between January 2011 and June 2016 collected from a national database. Outcomes were compared with a propensity score-matched analysis of pediatric inpatients administered IV opioids without IV acetaminophen (control) and those administered IV acetaminophen prior to IV opioids (intervention). Data were analyzed from January 2020 through October 2021. Exposures: Patients in the intervention group received IV acetaminophen prior to IV opioids. Patients in the control group received IV opioids without IV acetaminophen. Main Outcomes and Measures: Total duration of all IV opioids administered during a patient's hospitalization. Results: Of 893 293 pediatric inpatients, a total of 104 579 were included in analysis (median [IQR] age, 1.3 [0-14.7] years; 59 806 [57.2%] female; 21 485 [21.5%] African American, 56 309 [53.8%] White), of whom 18 197 (2.0%) received IV acetaminophen, and 287 504 (34.0%) received IV opioids. After applying exclusion criteria, among patients who received IV acetaminophen, 1739 (10.8%) received IV acetaminophen prior to IV opioids within a median (IQR) treatment time of 1.5 (0.02-7.3) hours. After propensity score matching produced comparable groups in the control and intervention groups (with 839 patients in each group), the multivariable model estimated a 15.5% shorter duration of IV opioid use in the intervention group, with an absolute IV opioid reduction of 7.5 hours (95% CI, 0.7-15.8 hours). Conclusions and Relevance: In this comparative effectiveness study, IV acetaminophen administered prior to IV opioids was associated with a reduction in IV opioid duration by 15.5%. Multimodal pain regimens that use IV acetaminophen prior to IV opioids could reduce IV opioid duration.

Predicting Future Care Requirements Using Machine Learning for Pediatric Intensive and Routine Care Inpatients.

Develop and compare separate prediction models for ICU and non-ICU care for hospitalized children in four future time periods (6-12, 12-18, 18-24, and 24-30 hr) and assess these models in an independent cohort and simulated children's hospital. DESIGN: Predictive modeling used cohorts from the Health Facts database (Cerner Corporation, Kansas City, MO). SETTING: Children hospitalized in ICUs. PATIENTS: Children with greater than or equal to one ICU admission (n = 20,014) and randomly selected routine care children without ICU admission (n = 20,130) from 2009 to 2016 were used for model development and validation. An independent 2017-2018 cohort consisted of 80,089 children. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Initially, we undersampled non-ICU patients for development and comparison of the models. We randomly assigned 64% of patients for training, 8% for validation, and 28% for testing in both clinical groups. Two additional validation cohorts were tested: a simulated children's hospitals and the 2017-2018 cohort. The main outcome was ICU care or non-ICU care in four future time periods based on physiology, therapy, and care intensity. Four independent, sequential, and fully connected neural networks were calibrated to risk of ICU care at each time period. Performance for all models in the test sample were comparable including sensitivity greater than or equal to 0.727, specificity greater than or equal to 0.885, accuracy greater than 0.850, area under the receiver operating characteristic curves greater than or equal to 0.917, and all had excellent calibration (all R2 s > 0.98). Model performance in the 2017-2018 cohort was sensitivity greater than or equal to 0.545, specificity greater than or equal to 0.972, accuracy greater than or equal to 0.921, area under the receiver operating characteristic curves greater than or equal to 0.946, and R2 s greater than or equal to 0.979. Performance metrics were comparable for the simulated children's hospital and for hospitals stratified by teaching status, bed numbers, and geographic location. CONCLUSIONS: Machine learning models using physiology, therapy, and care intensity predicting future care needs had promising performance metrics. Notably, performance metrics were similar as the prediction time periods increased from 6-12 hours to 24-30 hours.

Impact of Anaerobic Antibacterial Spectrum on Cystic Fibrosis Airway Microbiome Diversity and Pulmonary Function.

BACKGROUND: The role of anaerobic organisms in the cystic fibrosis (CF) lung microbiome is unclear. Our objectives were to investigate the effect of broad (BS) versus narrow (NS) spectrum antianaerobic antibiotic activity on lung microbiome diversity and pulmonary function, hypothesizing that BS antibiotics would cause greater change in microbiome diversity without a significant improvement in lung function. METHODS: Pulmonary function tests and respiratory samples were collected prospectively in persons with CF before and after treatment for pulmonary exacerbations. Treatment antibiotics were classified as BS or NS. Gene sequencing data from 16S rRNA were used for diversity analysis and bacterial genera classification. We compared the effects of BS versus NS on diversity indices, lung function and anaerobic/aerobic ratios. Statistical significance was determined by multilevel mixed-effects generalized linear models and mixed-effects regression models. RESULTS: Twenty patients, 6-20 years of age, experienced 30 exacerbations. BS therapy had a greater effect on beta diversity than NS therapy when comparing time points before antibiotics to after and at recovery. After antibiotics, the NS therapy group had a greater return toward baseline forced expiratory volume at 1 second and forced expiratory flow 25%-75% values than the BS group. The ratio of anaerobic/aerobic organisms showed a predominance of anaerobes in the NS group with aerobes dominating in the BS group. CONCLUSIONS: BS antianaerobic therapy had a greater and possibly longer lasting effect on the lung microbiome of persons with CF, without achieving the recovery of pulmonary function seen with the NS therapy. Specific antibiotic therapies may affect disease progression by changing the airway microbiome.

Multisystem Inflammatory Syndrome of Children: Subphenotypes, Risk Factors, Biomarkers, Cytokine Profiles, and Viral Sequencing.

OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. CONCLUSIONS: This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.

Contemporary Outcomes in Tetralogy of Fallot With Absent Pulmonary Valve After Fetal Diagnosis.

Background Tetralogy of Fallot with absent pulmonary valve is associated with high mortality, but it remains difficult to predict outcomes prenatally. We aimed to identify risk factors for mortality in a large multicenter cohort. Methods and Results Fetal echocardiograms and clinical data from 19 centers over a 10-year period were collected. Primary outcome measures included fetal demise and overall mortality. Of 100 fetuses, pregnancy termination/postnatal nonintervention was elected in 22. Of 78 with intention to treat, 7 (9%) died in utero and 21 (27%) died postnatally. With median follow-up of 32.9 months, no deaths occurred after 13 months. Of 80 fetuses with genetic testing, 46% had chromosomal abnormalities, with 22q11.2 deletion in 35%. On last fetal echocardiogram, at a median of 34.6 weeks, left ventricular dysfunction independently predicted fetal demise (odds ratio [OR], 7.4; 95% CI 1.3, 43.0; P=0.026). Right ventricular dysfunction independently predicted overall mortality in multivariate analysis (OR, 7.9; 95% CI 2.1-30.0; P=0.002). Earlier gestational age at delivery, mediastinal shift, left ventricular/right ventricular dilation, left ventricular dysfunction, tricuspid regurgitation, and Doppler abnormalities were associated with fetal and postnatal mortality, although few tended to progress throughout gestation on serial evaluation. Pulmonary artery diameters did not correlate with outcomes. Conclusions Perinatal mortality in tetralogy of Fallot with absent pulmonary valve remains high, with overall survival of 64% in fetuses with intention to treat. Right ventricular dysfunction independently predicts overall mortality. Left ventricular dysfunction predicts fetal mortality and may influence prenatal management and delivery planning. Mediastinal shift may reflect secondary effects of airway obstruction and abnormal lung development and is associated with increased mortality.