Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Hospitalization Among Adults Aged ≥18 Years with Immunocompromising Conditions - VISION Network, September 2023-February 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. As with past COVID-19 vaccines, additional doses may be considered for persons with immunocompromising conditions, who are at higher risk for severe COVID-19 and might have decreased response to vaccination. In this analysis, vaccine effectiveness (VE) of an updated COVID-19 vaccine dose against COVID-19-associated hospitalization was evaluated during September 2023-February 2024 using data from the VISION VE network. Among adults aged ≥18 years with immunocompromising conditions, VE against COVID-19-associated hospitalization was 38% in the 7-59 days after receipt of an updated vaccine dose and 34% in the 60-119 days after receipt of an updated dose. Few persons (18%) in this high-risk study population had received updated COVID-19 vaccine. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccination; persons with immunocompromising conditions may get additional updated COVID-19 vaccine doses ≥2 months after the last recommended COVID-19 vaccine.

Critical Care Utilization in Children With Cancer: U.S. Pediatric Health Information System Database Cohort 2012-2021.

OBJECTIVES: To determine changes in pediatric oncology hospitalizations requiring intensive care over the period 2012-2021. DESIGN: Retrospective study of hospital admission. SETTING: Registry data from 36 children's hospitals in the U.S. Pediatric Health Information Systems database. PATIENTS: Children 18 years or younger admitted to any of 36 hospitals with an oncology diagnosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 55,827 unique patients accounted for 281,221 pediatric oncology hospitalizations over the 10-year period, and 16.6% of hospitalizations included admission to the PICU. Hospitalizations and PICU admissions steadily increased over this decade. Between 2012 and 2016, 15.1% of oncology hospitalizations were admitted to the PICU compared with 18.0% from 2017 to 2021 (difference 2.9% [95% CI, 2.6-3.2%] p ≤ 0.0001). Support with invasive mechanical ventilation also increased over time with 3.7% during 2012-2016 compared with 4.1% from 2017 to 2021 (difference 0.4% [95% CI, 0.2-0.5%] p ≤ 0.0001). Similar results were seen with cardiorespiratory life support using extracorporeal membrane oxygenation (difference 0.05% [95% CI, 0.02-0.07%] p = 0.0002), multiple vasoactive agent use (difference 0.3% [95% CI, 0.2-0.4%] p < 0.0001), central line placement (difference 5.3% [95% CI, 5.1-5.6%], p < 0.001), and arterial line placement (difference 0.4% [95% CI, 0.3-0.4%], p < 0.001). Year-on-year case fatality rate was unchanged over time (1.3%), but admission to the PICU during the second 5 years, compared with the first 5 years, was associated with lower odds of mortality (difference 0.7% [95% CI, 0.3-1.1%]) (odds ratio 0.82 [95% CI, 0.75-0.90%] p < 0.001). CONCLUSIONS: The percentage of pediatric oncology hospitalizations resulting in PICU admission has increased over the past 10 years. Despite the increasing use of PICU admission and markers of acuity, and on comparing 2017-2021 with 2012-2016, there are lower odds of mortality.

Wide Institutional Variability in the Treatment of Pediatric Critical Asthma: A Multicenter Retrospective Study.

OBJECTIVES: Children with status asthmaticus refractory to first-line therapies of systemic corticosteroids and inhaled beta-agonists often receive additional treatments. Because there are no national guidelines on the use of asthma therapies in the PICU, we sought to evaluate institutional variability in the use of adjunctive asthma treatments and associations with length of stay (LOS) and PICU use. DESIGN: Multicenter retrospective cohort study. SETTING: Administrative data from the Pediatric Health Information Systems (PHIS) database. PATIENTS: All inpatients 2-18 years old were admitted to a PHIS hospital between 2013 and 2021 with a diagnostic code for asthma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study included 213,506 inpatient encounters for asthma, of which 29,026 patient encounters included care in a PICU from 39 institutions. Among these PICU encounters, large variability was seen across institutions in both the number of adjunctive asthma therapies used per encounter (min: 0.6, median: 1.7, max: 2.5, p < 0.01) and types of adjunctive asthma therapies (aminophylline, ipratropium, magnesium, epinephrine, and terbutaline) used. The center-level median hospital LOS ranged from 1 (interquartile range [IQR]: 1, 3) to 4 (3, 6) days. Among all the 213,506 inpatient encounters for asthma, the range of asthma admissions that resulted in PICU admission varied between centers from 5.2% to 47.3%. The average number of adjunctive therapies used per institution was not significantly associated with hospital LOS ( p = 0.81) nor the percentage of encounters with PICU admission ( p = 0.47). CONCLUSIONS: Use of adjunctive therapies for status asthmaticus varies widely among large children's hospitals and was not associated with hospital LOS or the percentage of encounters with PICU admission. Wide variance presents an opportunity for standardizing care with evidence-based guidelines to optimize outcomes and decrease adverse treatment effects and hospital costs.

Suicide and Self-Harm in Adolescents During the COVID-19 Pandemic: A U.S. Virtual Pediatric Systems, LLC, Database Study of PICU Admissions, 2016-2021.

OBJECTIVES: To characterize the epidemiology of suicide and self-harm among adolescents admitted to PICUs during the first 2 years of the COVID-19 pandemic in the United States. DESIGN: Descriptive analysis of a large, multicenter, quality-controlled database (Virtual Pediatric Systems [VPS]), and of a national public health dataset (U.S. Centers for Disease Control and Prevention web-based Wide-ranging ONline Data for Epidemiology Research [CDC WONDER]). SETTING: The 69 PICUs participating in the VPS database that contributed data for the entire the study period, January 1, 2016, to December 31, 2021. PATIENTS: Adolescents older than 12 years to younger than 18 years old admitted to a participating PICU during the study period with a diagnosis involving self-harm or a suicide attempt (VPS sample), or adolescent suicide deaths over the same period (CDC WONDER sample). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 10,239 suicide deaths and 7,692 PICU admissions for self-harm, including 5,414 admissions in the pre-pandemic period (Q1-2016 to Q1-2020) and 2,278 in the pandemic period (Q2-2020 to Q4-2021). Compared with the pre-pandemic period, there was no increase in the median (interquartile range) number of suicide deaths per quarter (429 [399-453] vs. 416 [390-482]) or PICU admissions for self-harm per quarter (315 [289-353] vs. 310 [286-387]) during the pandemic period, respectively. There was an increase in the ratio of self-harm PICU admissions to all-cause PICU admissions per quarter during the pandemic (1.98 [1.43-2.12]) compared with the pre-pandemic period per quarter (1.59 [1.46-1.74]). We also observed a significant decrease in all-cause PICU admissions per quarter early in the pandemic compared with the pre-pandemic period (16,026 [13,721-16,297] vs. 19,607 [18,371-20,581]). CONCLUSIONS: The number of suicide deaths and PICU admissions per quarter for self-harm remained relatively constant during the pandemic, while the number of all-cause PICU admissions per quarter decreased compared with the pre-pandemic period. The resultant higher ratio of self-harm admissions to all-cause PICU admissions may have contributed to the perception that more adolescents required critical care for mental health-related conditions early in the pandemic.

Biomarker Assessment of a High-Risk, Data-Driven Pediatric Sepsis Phenotype Characterized by Persistent Hypoxemia, Encephalopathy, and Shock.

OBJECTIVES: Identification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. We sought to the determine reproducibility of the data-driven "persistent hypoxemia, encephalopathy, and shock" (PHES) phenotype and determine its association with inflammatory and endothelial biomarkers, as well as biomarker-based pediatric risk strata. DESIGN: We retrained and validated a random forest classifier using organ dysfunction subscores in the 2012-2018 electronic health record (EHR) dataset used to derive the PHES phenotype. We used this classifier to assign phenotype membership in a test set consisting of prospectively (2003-2023) enrolled pediatric septic shock patients. We compared profiles of the PERSEVERE family of biomarkers among those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk strata. SETTING: Twenty-five PICUs across the United States. PATIENTS: EHR data from 15,246 critically ill patients with sepsis-associated MODS split into derivation and validation sets and 1,270 pediatric septic shock patients in the test set of whom 615 had complete biomarker data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The area under the receiver operator characteristic curve of the modified classifier to predict PHES phenotype membership was 0.91 (95% CI, 0.90-0.92) in the EHR validation set. In the test set, PHES phenotype membership was associated with both increased adjusted odds of complicated course (adjusted odds ratio [aOR] 4.1; 95% CI, 3.2-5.4) and 28-day mortality (aOR of 4.8; 95% CI, 3.11-7.25) after controlling for age, severity of illness, and immunocompromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and were more likely to be stratified as high risk based on PERSEVERE biomarkers predictive of death and persistent MODS. CONCLUSIONS: The PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlapped with higher risk strata based on prospectively validated biomarker approaches.

The Pediatric Data Science and Analytics Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network: Use of Supervised Machine Learning Applications in Pediatric Critical Care Medicine Research.

OBJECTIVE: Perform a scoping review of supervised machine learning in pediatric critical care to identify published applications, methodologies, and implementation frequency to inform best practices for the development, validation, and reporting of predictive models in pediatric critical care. DESIGN: Scoping review and expert opinion. SETTING: We queried CINAHL Plus with Full Text (EBSCO), Cochrane Library (Wiley), Embase (Elsevier), Ovid Medline, and PubMed for articles published between 2000 and 2022 related to machine learning concepts and pediatric critical illness. Articles were excluded if the majority of patients were adults or neonates, if unsupervised machine learning was the primary methodology, or if information related to the development, validation, and/or implementation of the model was not reported. Article selection and data extraction were performed using dual review in the Covidence tool, with discrepancies resolved by consensus. SUBJECTS: Articles reporting on the development, validation, or implementation of supervised machine learning models in the field of pediatric critical care medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5075 identified studies, 141 articles were included. Studies were primarily (57%) performed at a single site. The majority took place in the United States (70%). Most were retrospective observational cohort studies. More than three-quarters of the articles were published between 2018 and 2022. The most common algorithms included logistic regression and random forest. Predicted events were most commonly death, transfer to ICU, and sepsis. Only 14% of articles reported external validation, and only a single model was implemented at publication. Reporting of validation methods, performance assessments, and implementation varied widely. Follow-up with authors suggests that implementation remains uncommon after model publication. CONCLUSIONS: Publication of supervised machine learning models to address clinical challenges in pediatric critical care medicine has increased dramatically in the last 5 years. While these approaches have the potential to benefit children with critical illness, the literature demonstrates incomplete reporting, absence of external validation, and infrequent clinical implementation.

Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID-19-Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions - VISION Network, September 2022-April 2023.

On September 1, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended a single bivalent mRNA COVID-19 booster dose for persons aged ≥12 years who had completed at least a monovalent primary series. Early vaccine effectiveness (VE) estimates among adults aged ≥18 years showed receipt of a bivalent booster dose provided additional protection against COVID-19-associated emergency department and urgent care visits and hospitalizations compared with that in persons who had received only monovalent vaccine doses (1); however, insufficient time had elapsed since bivalent vaccine authorization to assess the durability of this protection. The VISION Network* assessed VE against COVID-19-associated hospitalizations by time since bivalent vaccine receipt during September 13, 2022-April 21, 2023, among adults aged ≥18 years with and without immunocompromising conditions. During the first 7-59 days after vaccination, compared with no vaccination, VE for receipt of a bivalent vaccine dose among adults aged ≥18 years was 62% (95% CI = 57%-67%) among adults without immunocompromising conditions and 28% (95% CI = 10%-42%) among adults with immunocompromising conditions. Among adults without immunocompromising conditions, VE declined to 24% (95% CI = 12%-33%) among those aged ≥18 years by 120-179 days after vaccination. VE was generally lower for adults with immunocompromising conditions. A bivalent booster dose provided the highest protection, and protection was sustained through at least 179 days against critical outcomes, including intensive care unit (ICU) admission or in-hospital death. These data support updated recommendations allowing additional optional bivalent COVID-19 vaccine doses for certain high-risk populations. All eligible persons should stay up to date with recommended COVID-19 vaccines.

The influence of social and environmental determinants of health on hospitalizations for pediatric asthma.

BACKGROUND: Asthma is the most common chronic disease of childhood, and has several social, environmental, and demographic factors potentially influential to its disease burden. This study sought to determine the influence of these factors on hospital admissions and readmissions for pediatric asthma. METHODS: This was a retrospective cohort study using data from the Indiana Network for Patient Care, a state-wide health information exchange in the United States. Study participants were children 2-18 years old admitted to the hospital with a respiratory diagnostic code between 2010 and 2021. Clinical variables were obtained from electronic health record data, and social and environmental determinants of health data were obtained from the Indiana Social Assets and Vulnerabilities Indicators using geocoding systems. Negative binomial models were used to examine community level social and environmental risk factors modifying the relationship between patient characteristics and the risk of asthma-related hospitalizations and 30-day readmissions. RESULTS: The study sample included 25,063 patients with an average follow-up of 9 (SD = 5) years. Of these, there were 17,816 asthma-related admissions. There were a total of 1,037 asthma-related 30-day readmissions, with an incidence rate of readmissions relative to total visits of 0.028 per person-year. A high social vulnerability index (SVI) was associated with an increased rate of hospital admissions (Proportion attributable ratio: 1.09, 95%CI (1.03,1.15), p < 0.05). No environmental determinants of health were significantly associated with hospitalization rate. CONCLUSION: High SVI was significantly associated with increased risk of total hospital admissions for pediatric asthma.

Derivation, Validation, and Clinical Relevance of a Pediatric Sepsis Phenotype With Persistent Hypoxemia, Encephalopathy, and Shock.

OBJECTIVES: Untangling the heterogeneity of sepsis in children and identifying clinically relevant phenotypes could lead to the development of targeted therapies. Our aim was to analyze the organ dysfunction trajectories of children with sepsis-associated multiple organ dysfunction syndrome (MODS) to identify reproducible and clinically relevant sepsis phenotypes and determine if they are associated with heterogeneity of treatment effect (HTE) to common therapies. DESIGN: Multicenter observational cohort study. SETTING: Thirteen PICUs in the United States. PATIENTS: Patients admitted with suspected infections to the PICU between 2012 and 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used subgraph-augmented nonnegative matrix factorization to identify candidate trajectory-based phenotypes based on the type, severity, and progression of organ dysfunction in the first 72 hours. We analyzed the candidate phenotypes to determine reproducibility as well as prognostic, therapeutic, and biological relevance. Overall, 38,732 children had suspected infection, of which 15,246 (39.4%) had sepsis-associated MODS with an in-hospital mortality of 10.1%. We identified an organ dysfunction trajectory-based phenotype (which we termed persistent hypoxemia, encephalopathy, and shock) that was highly reproducible, had features of systemic inflammation and coagulopathy, and was independently associated with higher mortality. In a propensity score-matched analysis, patients with persistent hypoxemia, encephalopathy, and shock phenotype appeared to have HTE and benefit from adjuvant therapy with hydrocortisone and albumin. When compared with other high-risk clinical syndromes, the persistent hypoxemia, encephalopathy, and shock phenotype only overlapped with 50%-60% of patients with septic shock, moderate-to-severe pediatric acute respiratory distress syndrome, or those in the top tier of organ dysfunction burden, suggesting that it represents a nonsynonymous clinical phenotype of sepsis-associated MODS. CONCLUSIONS: We derived and validated the persistent hypoxemia, encephalopathy, and shock phenotype, which is highly reproducible, clinically relevant, and associated with HTE to common adjuvant therapies in children with sepsis.

Ten year trends in hospital encounters for pediatric asthma: an Indiana experience.

INTRODUCTION: Pediatric asthma is a common cause of emergency department visits, hospital admissions, and mortality. Population incidence studies have historically used large-scale survey data. We measured these epidemiologic trends using a health information exchange. METHODS: In this retrospective cohort study, we used electronic health record data from a regional health information exchange to study clinical trends in pediatric patients presenting to the hospital for asthma in the State of Indiana. Data was obtained from 2010 to 2019 and included all patients ages 2-18 years. Study participants were identified using international classification of disease codes. The measured outcomes were number of hospital encounters per year, percentage of admissions per year, and mortality rates. RESULTS: Data included 50,393 unique patients and 88,772 unique encounters, with 57% male patients. Over the ten-year period, hospital encounters ranged from 5000 to 8000 per year with no change in trajectory. Between 2010 and 2012, the percent of encounters admitted to the hospital was ∼30%. This decreased to ∼20-25% for 2015-2019. Patient mortality rates increased from 1 to 3 per 1000 patient encounters in 2010-2014 to between 5 and 7 per 1000 patient encounters from 2016 to 2019. White patients had a significantly higher admission percentage compared to other racial groups, but no difference in mortality rate. CONCLUSIONS: Asthma continues to be a common condition requiring hospital care for pediatric patients. Regional health information exchanges can enable public health researchers to follow asthma trends in near real time, and have potential for informing patient-level public health interventions.

Epidemiology of Pediatric Critical Care Admissions in 43 United States Children's Hospitals, 2014-2019.

OBJECTIVES: To identify trends in the population of patients in PICUs over time. DESIGN: Cross-sectional, retrospective cohort study using the Pediatric Health Information System database. SETTING: Forty-three U.S. children's hospitals. PATIENTS: All patients admitted to Pediatric Health Information System-participating hospitals from January 2014 to December 2019. Individuals greater than 65 years old and normal newborns were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PICU care occurred in 13.8% of all pediatric hospital encounters and increased over the study period from 13.3% to 14.3%. Resource intensity, based on average Hospitalization Resource Intensity Scores for Kids score, increased significantly across epochs (6.5 in 2014-2015 vs 6.9 in 2018-2019; p < 0.001), although this was not consistently manifested as additional procedural exposure. Geometric mean PICU cost per patient encounter was stable. The two most common disease categories in PICU patients were respiratory failure and cardiac and circulatory congenital anomalies. Of all PICU encounters, 35.5% involved mechanical ventilation, and 25.9% involved vasoactive infusions. Hospital-level variation in the percentage of days spent in the PICU ranged from 15.1% to 63.5% across the participating sites. Of the total hospital costs for patients admitted to the PICU, 41.7% of costs were accrued during the patients' PICU stay. CONCLUSIONS: The proportional use of PICU beds is increasing over time, although was variable across centers. Case-based resource use and complexity of pediatric patients are also increasing. Despite the higher use of PICU resources, the standardized costs of PICU care per patient encounter have remained stable. These data may help to inform current PICU resource allocation and future PICU capacity planning.

School Closures in the United States and Severe Respiratory Illnesses in Children: A Normalized Nationwide Sample.

OBJECTIVES: To determine the association between nationwide school closures and prevalence of common admission diagnoses in the pediatric critical care unit. DESIGN: Retrospective cohort study. SETTING: National database evaluation using the Virtual Pediatric Systems LLC database. PATIENTS: All patients admitted to the PICU in 81 contributing hospitals in the United States. MEASUREMENTS AND MAIN RESULTS: Diagnosis categories were determined for all 110,418 patients admitted during the 20-week study period in each year (2018, 2019, and 2020). Admission data were normalized relative to statewide school closure dates for each patient using geographic data. The "before school closure" epoch was defined as 8 weeks prior to school closure, and the "after school closure" epoch was defined as 12 weeks following school closure. For each diagnosis, admission ratios for each study day were calculated by dividing 2020 admissions by 2018-2019 admissions. The 10 most common diagnosis categories were examined. Significant changes in admission ratios were identified for bronchiolitis, pneumonia, and asthma. These changes occurred at 2, 8, and 35 days following school closure, respectively. PICU admissions decreased by 82% for bronchiolitis, 76% for pneumonia, and 76% for asthma. Nonrespiratory diseases such as diabetic ketoacidosis, status epilepticus, traumatic injury, and poisoning/ingestion did not show significant changes following school closure. CONCLUSIONS: School closures are associated with a dramatic reduction in the prevalence of severe respiratory disease requiring PICU admission. School closure may be an effective tool to mitigate future pandemics but should be balanced with potential academic, economic, mental health, and social consequences.

Characteristics and Outcomes of Critically Ill Children With Multisystem Inflammatory Syndrome.

OBJECTIVES: To characterize the prevalence of pediatric critical illness from multisystem inflammatory syndrome in children (MIS-C) and to assess the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain on outcomes. DESIGN: Retrospective cohort study. SETTING: Database evaluation using the Virtual Pediatric Systems Database. PATIENTS: All children with MIS-C admitted to the PICU in 115 contributing hospitals between January 1, 2020, and June 30, 2021. MEASUREMENTS AND MAIN RESULTS: Of the 145,580 children admitted to the PICU during the study period, 1,338 children (0.9%) were admitted with MIS-C with the largest numbers of children admitted in quarter 1 (Q1) of 2021 ( n = 626). The original SARS-CoV-2 viral strain and the D614G Strain were the predominant strains through 2020, with Alpha B.1.1.7 predominating in Q1 and quarter 2 (Q2) of 2021. Overall, the median PICU length of stay (LOS) was 2.7 days (25-75% interquartile range [IQR], 1.6-4.7 d) with a median hospital LOS of 6.6 days (25-75% IQR, 4.7-9.3 d); 15.2% received mechanical ventilation with a median duration of mechanical ventilation of 3.1 days (25-75% IQR, 1.9-5.8 d), and there were 11 hospital deaths. During the study period, there was a significant decrease in the median PICU and hospital LOS and a decrease in the frequency of mechanical ventilation, with the most significant decrease occurring between quarter 3 and quarter 4 (Q4) of 2020. Children admitted to a PICU from the general care floor or from another ICU/step-down unit had longer PICU LOS than those admitted directly from an emergency department. CONCLUSIONS: Overall mortality from MIS-C was low, but the disease burden was high. There was a peak in MIS-C cases during Q1 of 2021, following a shift in viral strains in Q1 of 2021. However, an improvement in MIS-C outcomes starting in Q4 of 2020 suggests that viral strain was not the driving factor for outcomes in this population.

The Heparin-Antithrombin Product: A Novel Value for Pediatric Extracorporeal Anticoagulation.

Hematologic complications are a source of morbidity and mortality for patients receiving extracorporeal membrane oxygenation (ECMO) support. There is no consensus strategy for monitoring anticoagulation for children supported with ECMO. This study evaluated a novel measurement of anticoagulation for children on ECMO. This was a single-center observational study of children supported with ECMO from 2015 to 2020. Each patient's current unfractionated heparin dose was multiplied by the current antithrombin III (AT) level to obtain a novel anticoagulation value, the heparin-antithrombin product (HAP). This value was compared with the heparin dose, AT, and activated clotting time (ACT) to predict anti-Xa value using linear correlation and decision tree methods. Data were obtained from 128 patients supported with ECMO. The HAP value was more highly correlated with anti-Xa level than heparin dose, AT level, and ACT. This correlation was highest in the neonatal population (r = .7). The variable importance metrics from the regression tree and random forest models both identified the HAP value as the most influential predictor variable for anti-Xa value. The HAP value is more highly correlated with the anti-Xa level than heparin dose, AT level, or ACT. Further research is needed to evaluate the effectiveness of the HAP value as a measurement of anticoagulation for children on ECMO.

Epidemiologic Trends In Children With Toxicologic Exposures Requiring Intensive Care Before and During the COVID-19 Pandemic.

OBJECTIVE: Pediatric poison exposures are a common reason for pediatric intensive care unit (PICU) -admission. The purpose of this study was to examine the exposure trends and patient outcomes in 2018-2019 compared with 2020-2021 amidst the COVID-19 pandemic. METHODS: This was a retrospective cohort study of patients 18 years of age or younger with a suspected toxicologic exposure from January 2018 to March 2021. The primary endpoint was rate of PICU admissions between the 2 cohorts. Secondary endpoints included medical outcome stratified by severity, PICU length of stay, and need for mechanical ventilation. RESULTS: Our study included a total of 340 patients with median age 14.5 (IQR, 11.9-16.1) years. There was no significant difference in age, sex, or race between the 2 cohorts. The percentage of patients admitted to the PICU for poison exposures was significantly higher in the COVID-19 cohort compared with the pre-COVID-19 cohort (8.4% vs 3.7%, p < 0.01). Severity of medical outcomes differed between the groups; the COVID-19 cohort had more extreme clinical presentations of no effect or death (p < 0.01). No significant difference was found among the remaining secondary outcomes. Classes of substances ingested were comparable with baseline poison center data. CONCLUSIONS: Poisoning-related PICU admissions occurred at more than twice the pre-pandemic rate. This may emphasize the effect of the COVID-19 pandemic on pediatric access and exposure to poisons.

Noninvasive Respiratory Support for Pediatric Critical Asthma: A Multicenter Cohort Study.

BACKGROUND: Noninvasive respiratory support (NRS) for pediatric critical asthma includes CPAP; bi-level positive airway pressure (BPAP); and heated, humidified, high-flow nasal cannula (HFNC). We used the Virtual Pediatric System database to estimate NRS by prescribing rates for pediatric critical asthma and characterize patient clinical features and in-patient outcomes by the initial NRS device applied. METHODS: We performed a retrospective cohort study from 125 participating pediatric ICUs among children 2-17 years of age hospitalized for critical asthma and prescribed NRS from 2017 through 2021. The primary outcomes were NRS modality prescribing rates and trends. Secondary outcomes were descriptive and included demographics, comorbidities, severity of illness indices, and NRS failure rates (defined as escalation from the initial NRS modality to invasive ventilation, HFNC to BPAP or CPAP, or CPAP to BPAP). RESULTS: Of the 10,083 encounters studied, the initial NRS modalities prescribed varied widely by hospital center (HFNC: 69.7 ± 29.6%; BPAP: 27.2 ± 7.1%; CPAP: 3.1 ± 5.9%). The mean rates of HFNC use increased from 59.7% in 2017 to 71.9% in 2021 (+2.5%/y). In contrast, BPAP (-1.6%/y) and CPAP (-0.8%/y) utilization declined throughout the study period. Older children who were obese and with a higher Pediatric Risk of Mortality III-Probability of Mortality score were more frequently prescribed BPAP and CPAP compared with HFNC. Those children on HFNC experienced higher noninvasive respiratory support failure rates versus BPAP (7.3% vs 2.4%; P < .001) but a lower subsequent invasive ventilation rate versus BPAP (0.8% vs 2.4%; P < .001). CONCLUSIONS: In this multi-center cohort study, we observed that children with critical asthma are increasingly exposed to HFNC compared with BPAP and CPAP. Rates of HFNC failure were greater than those of BPAP failure, but a majority were transitioned to BPAP without subsequent invasive ventilation. The next steps include prospective trials, including practical end points such as patient comfort and optimal delivery of nebulized treatments to distinguish device superiority and suitable NRS utilization.

Institutional Variability in Respiratory Support Use for Pediatric Critical Asthma: A Multicenter Retrospective Study.

Rationale: Over 20,000 children are hospitalized in the United States for asthma every year. Although initial treatment guidelines are well established, there is a lack of high-quality evidence regarding the optimal respiratory support devices for these patients.Objectives: The objective of this study was to evaluate institutional and temporal variability in the use of respiratory support modalities for pediatric critical asthma.Methods: We conducted a retrospective cohort study using data from the Virtual Pediatrics Systems database. Our study population included children older than 2 years old admitted to a VPS contributing pediatric intensive care unit from January 2012 to December 2021 with a primary diagnosis of asthma or status asthmaticus. We evaluated the percentage of encounters using a high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive bilevel positive pressure ventilation (NIV), and invasive mechanical ventilation (IMV) for all institutions, then divided institutions into quintiles based on the volume of patients. We created logistic regression models to determine the influence of institutional volume and year of admission on respiratory support modality use. We also conducted time-series analyses using Kendall's tau.Results: Our population included 77,115 patient encounters from 163 separate institutions. Institutional use of respiratory modalities had significant variation in HFNC (28.3%, interquartile range [IQR], 11.0-49.0%; P < 0.01), CPAP (1.4%; IQR, 0.3-4.3%; P < 0.01), NIV (8.6%; IQR, 3.5-16.1%; P < 0.01), and IMV (5.1%; IQR, 3.1-8.2%; P < 0.01). Increased institutional patient volume was associated with significantly increased use of NIV (odds ratio [OR], 1.33; 1.29-1.36; P < 0.01) and CPAP (OR, 1.20; 1.15-1.25; P < 0.01), and significantly decreased use of HFNC (OR, 0.80; 0.79-0.81; P < 0.01) and IMV (OR, 0.82; 0.79-0.86; P < 0.01). Time was also associated with a significant increase in the use of HFNC (11.0-52.3%; P < 0.01), CPAP (1.6-5.4%; P < 0.01), and NIV (3.7-21.2%; P < 0.01), whereas there was no significant change in IMV use (6.1-4.0%; P = 0.11).Conclusions: Higher-volume centers are using noninvasive positive pressure ventilation more frequently for pediatric critical asthma and lower frequencies of HFNC and IMV. Treatment with HFNC, CPAP, and NIV for this population is increasing in the last decade.

Learning competing risks across multiple hospitals: one-shot distributed algorithms.

OBJECTIVES: To characterize the complex interplay between multiple clinical conditions in a time-to-event analysis framework using data from multiple hospitals, we developed two novel one-shot distributed algorithms for competing risk models (ODACoR). By applying our algorithms to the EHR data from eight national children's hospitals, we quantified the impacts of a wide range of risk factors on the risk of post-acute sequelae of SARS-COV-2 (PASC) among children and adolescents. MATERIALS AND METHODS: Our ODACoR algorithms are effectively executed due to their devised simplicity and communication efficiency. We evaluated our algorithms via extensive simulation studies as applications to quantification of the impacts of risk factors for PASC among children and adolescents using data from eight children's hospitals including the Children's Hospital of Philadelphia, Cincinnati Children's Hospital Medical Center, Children's Hospital of Colorado covering over 6.5 million pediatric patients. The accuracy of the estimation was assessed by comparing the results from our ODACoR algorithms with the estimators derived from the meta-analysis and the pooled data. RESULTS: The meta-analysis estimator showed a high relative bias (∼40%) when the clinical condition is relatively rare (∼0.5%), whereas ODACoR algorithms exhibited a substantially lower relative bias (∼0.2%). The estimated effects from our ODACoR algorithms were identical on par with the estimates from the pooled data, suggesting the high reliability of our federated learning algorithms. In contrast, the meta-analysis estimate failed to identify risk factors such as age, gender, chronic conditions history, and obesity, compared to the pooled data. DISCUSSION: Our proposed ODACoR algorithms are communication-efficient, highly accurate, and suitable to characterize the complex interplay between multiple clinical conditions. CONCLUSION: Our study demonstrates that our ODACoR algorithms are communication-efficient and can be widely applicable for analyzing multiple clinical conditions in a time-to-event analysis framework.

EHR-based Case Identification of Pediatric Long COVID: A Report from the RECOVER EHR Cohort.

Objective: Long COVID, marked by persistent, recurring, or new symptoms post-COVID-19 infection, impacts children's well-being yet lacks a unified clinical definition. This study evaluates the performance of an empirically derived Long COVID case identification algorithm, or computable phenotype, with manual chart review in a pediatric sample. This approach aims to facilitate large-scale research efforts to understand this condition better. Methods: The algorithm, composed of diagnostic codes empirically associated with Long COVID, was applied to a cohort of pediatric patients with SARS-CoV-2 infection in the RECOVER PCORnet EHR database. The algorithm classified 31,781 patients with conclusive, probable, or possible Long COVID and 307,686 patients without evidence of Long COVID. A chart review was performed on a subset of patients (n=651) to determine the overlap between the two methods. Instances of discordance were reviewed to understand the reasons for differences. Results: The sample comprised 651 pediatric patients (339 females, M age = 10.10 years) across 16 hospital systems. Results showed moderate overlap between phenotype and chart review Long COVID identification (accuracy = 0.62, PPV = 0.49, NPV = 0.75); however, there were also numerous cases of disagreement. No notable differences were found when the analyses were stratified by age at infection or era of infection. Further examination of the discordant cases revealed that the most common cause of disagreement was the clinician reviewers' tendency to attribute Long COVID-like symptoms to prior medical conditions. The performance of the phenotype improved when prior medical conditions were considered (accuracy = 0.71, PPV = 0.65, NPV = 0.74). Conclusions: Although there was moderate overlap between the two methods, the discrepancies between the two sources are likely attributed to the lack of consensus on a Long COVID clinical definition. It is essential to consider the strengths and limitations of each method when developing Long COVID classification algorithms.