Epidemiology, Outcomes, and Trend Analysis of Hospitalized Infants With Respiratory Syncytial Virus (RSV) Bronchiolitis From 1997 to 2019.

Background  Most children with respiratory syncytial virus (RSV) infection have a self-limiting course that can be managed with supportive care, and hospitalization is uncommon. The objectives of this study were to evaluate the epidemiology, outcomes, associated comorbidities, and temporal trends in the prevalence of infants one to 24 months of age who required hospitalization for RSV infection in the United States of America from 1997 to 2019. Methods In this retrospective cross-sectional study, we utilized the Kids' Inpatient Database (KID) to investigate the prevalence and outcomes of RSV bronchiolitis within a large cohort of discharged patients from 1997 to 2019. We included children one to 24 months of age admitted with a diagnosis of RSV bronchiolitis. Neonates were excluded from the analysis. A chi-square for linear trend was used to analyze trends in the prevalence of RSV bronchiolitis hospitalization, the presence of complex chronic conditions (CCC), congenital heart disease (CHD), the use of non-invasive and invasive mechanical ventilation (NIV and IMV), and hospital mortality. Results There were a total of 566,786 infants aged one to 24 months hospitalized with RSV infection out of a total of 9,309,597 discharges during the eight-year cohort, with a hospital prevalence of 60.9 per 1000 discharges and a hospital mortality rate of 0.09% (95% confidence interval (CI): 0.08%-0.1%). There was no trend in hospitalization rates of RSV infections per 100,000 U.S. population during the study period, with a decrease in hospital mortality trend. Children with RSV bronchiolitis were more likely to have government insurance and reside in zip codes with the lowest income quartile. There was a significant seasonal and regional variation in RSV-related hospitalizations. The presence of CCC was identified in 2.4% of the RSV group compared to 5.1% of non-RSV discharges (odds ratio (OR): 0.46, 95% CI: 0.45-0.47; p<0.001). The prevalence of RSV among all discharges has significantly increased over the study period, rising from 51.6 cases per 1000 discharges in 1997 to 180.1 cases per 1000 discharges in 2019 (p<0.001). The prevalence of CCC and CHD among RSV patients has also shown an upward trend, with CCC cases increasing from 1,411 in 1997 to 2,795 in 2019 and CHD cases rising from 1,795 to 3,622 during the same period. The use of invasive mechanical ventilation, non-invasive ventilation, and extracorporeal membrane oxygenation has consistently increased over time. Additionally, complications such as the need for cardiopulmonary resuscitation have demonstrated a similar increasing trend, although they have remained overall low. However, population-based hospitalization rates showed no significant trend. Conclusions The hospitalization rates at a population level in the United States for RSV infection in children aged one to 24 months remained steady from 1997 to 2019, while hospital mortality rates showed a declining trend. There is an increased proportion of comorbid conditions and increased resource utilization in children with RSV. These findings are important for monitoring the effectiveness of preventive strategies for severe RSV infections.

Hematopoietic Stem Cell Transplantation in Children with Sickle Cell Disease and Thalassemia Major: A National Database Study.

In patients with sickle cell disease (SCD) and beta-thalassemia major (TM), allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment option with a good survival rate. However, with the recent approval of gene therapies, more information is needed to understand the benefits and risks of these interventions. We performed a retrospective analysis of the Kids Inpatient Database to describe demographic features, short-term complications, and hospital charges of patients with SCD and TM treated with HSCT during 2006-2019 in the United States. The database was filtered using the International Classification of Diseases, 9th and 10th edition codes to identify children under 20 years of age with SCD or TM who underwent HSCT. A total of 513 children with SCD or TM who received HSCT were analyzed. The prevalence of HSCT per 1000,000 U.S. population increased from 0.31 in 2006 to 1.99 in 2019 (p < 0.001). The median age of children with SCD who underwent HSCT was 10 (6-15) years, and that for TM was 6 (3-11.5) years (p < 0.001). The combined mortality rate was 4% (2.4%-6.6%) but higher in the TM group. The length-of-stay and total charges were higher in the TM population (p < 0.01). This study provides national data on HSCT among hospitalized children with SCD and TM in the United States, demonstrating an increasing use of HSCT between 2006 and 2019. Although hospital mortality of HSCT in these conditions is low, it still represents a challenge, especially in TM patients.

Characteristics and complications of acute promyelocytic leukemia in children: an analysis of a national database.

Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia (AML) that was previously one of the most fatal forms of acute leukemia. With advances in diagnosis and treatment, APL has become one of the most curable myeloid leukemias. The major reason for treatment failure in APL is early death after initiation of treatment. We performed a retrospective cross-sectional analysis of the Healthcare Cost and Utilization Project 2016 and 2019 Kids' Inpatient Database, with the diagnosis of APL or AML not in remission as defined by ICD-10-CM codes. We compared complications and outcomes associated with APL and AML (exclusive of APL) in hospitalized children in the U.S. and described yearly national incidence. The national incidence of APL was 2.2 cases per million children per year. Children with APL were more likely to have cardiopulmonary complications (OR 1.79; CI 1.20-2.67; p = 0.004), coagulation abnormalities or DIC (OR 7.75; CI 5.81-10.34; p < 0.001), pulmonary hemorrhage (OR 2.18; CI 1.49-3.17; p < 0.001), and intracranial hemorrhage (OR 10.82; CI 5.90-19.85; p < 0.001) and less likely to have infectious complications (OR 0.48; CI 0.34-0.67; p < 0.001) compared to children with AML. In-hospital mortality rates were similar in children with APL and AML (4.2% vs 2.6%; OR 1.62; CI 0.86-3.06; p = 0.13), while the median length of stay for children who died from APL was shorter compared to AML (2 (IQR: 1-7) versus 25 (IQR: 5-66) days; p < 0.05). Hemorrhagic complications occur more often, and infectious complications occur less often in hospitalized children with APL compared to AML.

Epidemiology of Adenovirus Infection in Hospitalized Children in the United States From 1997 to 2019.

OBJECTIVE: The study aimed to explore the prevalence, clinical features, resource utilization, temporal trends and outcomes associated with adenoviral infections in hospitalized children. METHODS: A retrospective analysis using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997 to 2019 was performed. Children 29 days to 17 years of age with adenoviral infection were selected. Chi-square, Kruskal-Wallis tests, linear trend analysis and multivariable analysis were used for data analysis. RESULTS: A total of 40,135 children under 18 years of age with adenoviral infection were discharged in the United States with an overall prevalence of 18.9 per 10,000 discharges and 6.9 children per 100,000 population. By linear trend analysis, the hospitalization rate has significantly increased with the highest prevalence in 2019. Adenoviral infection was more prevalent in Black children, in winter months, in the Midwest region, in children with government insurance and in the lowest income quartile. The majority (85%) of adenovirus-related hospitalizations occurred under 6 years of age. Mechanical ventilation, extracorporeal membrane oxygenation support, acute kidney injury and liver failure were documented in 11.9%, 0.4%, 2.7% and 0.4%, respectively. The overall case fatality rate was 1.4%, which decreased from 1997 to 2019 ( P < 0.05). By regression analysis, an increased mortality rate was associated with the need for mechanical ventilation, the presence of complex chronic conditions, immune deficiency, central nervous system infection and pneumonia/bronchiolitis. CONCLUSIONS: Most human adenovirus infections occur in children under 6 years of age and cause mild illness. Human adenovirus can lead to serious illness in children with complex chronic conditions and immune deficiency conditions.

Racial Inequities in Mortality Rate in Hospitalized Children.

BACKGROUND AND OBJECTIVES: Racial/ethnic inequities for inpatient mortality in children at a national level in the U.S. have not been explored. The objective of this study was to evaluate differences in inpatient mortality rate among different racial/ethnic groups, using the Kids' Inpatient Database. METHODS: A cross-sectional study of children of ages greater than 28 days and less than 21 years discharged during 2012 and 2016. Racial/ethnic groups - White, Black, Hispanic, Asian and Pacific Islander and Native Americans were analyzed in two cohorts, Cohort A (all discharges) and Cohort B (ventilated children). RESULTS: A total of 4,247,604 and 79,116 discharges were included in cohorts A and B, respectively. Univariate analysis showed that the inpatient mortality rate was highest among Asian and Pacific Islander children for both cohorts: A (0.47% [0.42-0.51]), B (10.9% [9.8-12.1]). Regression analysis showed that Asian and Pacific Islander and Black children had increased odds of inpatient mortality compared to White children: A (1.319 [1.162-1.496], 1.178 [1.105-1.257], respectively) and B (1.391 [1.199-1.613], 1.163 [1.079-1.255], respectively). Population-based hospital mortality was highest in Black children (1.17 per 10,000 children). CONCLUSIONS: Inpatient mortality rates are significantly higher in U.S. children of Asian and Pacific Islander and Black races compared to White children. U.S. population-based metrics such as hospitalization rate, ventilation rate, and hospital mortality rate are highest in Black children. Our data suggest that lower median household income alone may not account for a higher inpatient mortality rate. The causes and prevention of racial and ethnic inequities in hospitalized children need to be explored further.

A Neonate With Cytokine Storm Managed With Steroids, Therapeutic Plasma Exchange, and Tocilizumab.

Neonatal cytokine storms, though rare, can induce hyperinflammation due to elevated interleukin-6 (IL-6), triggering multiorgan failure. We present the case of a term male neonate necessitating extracorporeal membrane oxygenation (ECMO) post-birth for persistent pulmonary hypertension due to meconium aspiration syndrome. Three days after weaning from ECMO support, steroids and therapeutic plasma exchange were initiated due to deteriorating thrombocytopenia, oxygenation, hemodynamic instability, and increased C-reactive protein (CRP) and ferritin levels. Elevated IL-6 prompted tocilizumab administration after four days of daily plasmapheresis. Post-tocilizumab infusion, notable enhancements in platelet counts, oxygenation indices, and CRP were observed, resulting in stable discharge of the child. Comprehensive evaluations for infections, including coronavirus disease 2019, as well as genetic and metabolic disorders, yielded negative results.

Epidemiology and Outcomes of Cerebral Edema in Hospitalized Children.

BACKGROUND: Cerebral edema can be a consequence of multiple disease processes. Untreated cerebral edema can be fatal, and even with aggressive management, it can be devastating. The objective of this study was to describe the prevalence, underlying causes, and outcomes of cerebral edema in hospitalized children. METHODS: A retrospective cross-sectional study using the 2016 Kids' Inpatient Database was performed. Children aged one month to 20 years were included. Sample weighting was employed to produce national estimates. Univariate analyses were used to compare those who died and survived. Multivariable logistic regression was performed to assess the influence of demographic variables and etiologic factors on mortality. RESULTS: Cerebral edema was documented in 4903 children of 2,210,263 (2.2 of 1000) discharges. Among children with cerebral edema, males were 57%, white children were 47.9%, and adolescents were 48.9%. The three most common etiologies associated with cerebral edema in this cohort were stroke (21.7%), anoxic injury (21.4%), and central nervous system (CNS) malignancy (16%). The overall hospital mortality rate was 29.4%. The adjusted mortality rate was significantly higher when cerebral edema was associated with anoxic injury (84%). The mortality was lower when cerebral edema was associated with CNS malignancy (9.5%) or diabetic ketoacidosis (DKA) (4.3%). CONCLUSIONS: Cerebral edema is uncommon in hospitalized children but has a high mortality. Stroke and anoxic brain injury are the two most common etiologies for cerebral edema in hospitalized children in the United States. Among all etiologies for cerebral edema in children, anoxic brain injury has the highest mortality, whereas DKA has the lowest mortality.

Characteristics and Outcomes of Children with Cerebral Sinus Venous Thrombosis.

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is an uncommon condition in children with potentially serious outcomes. Large epidemiological studies in children with CSVT are few. The objective of this study is to evaluate the epidemiology and in-hospital outcomes of hospitalized children with CSVT in the United States. METHODS: We performed a retrospective cross-sectional analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database for the combined years 2016 and 2019. The database was queried using the diagnoses for intracranial and intraspinal phlebitis and thrombophlebitis, nonpyogenic thrombosis of the intracranial venous system, and cerebral infarction due to cerebral venous thrombosis. Sample weighting was employed to produce national estimates. RESULTS: Of 12,165,621 discharges, 3202 had CSVT (in-hospital prevalence 26.3 per 100,000 discharges). Male patients accounted for 57% of CSVT discharges. The median age was 8 years (interquartile range 1-16), with a U-shaped distribution with peaks in patients younger than 4 years and patients aged between 18 and 20 years. A total of 19.3% of children with CSVT had either hemorrhagic or ischemic stroke. Patients with stroke were more likely to require mechanical ventilation (odds ratio [OR] 2.7; 95% confidence interval [CI] 2.1-3.3; p < 0.001) and have higher mortality (OR 2.3; 95% CI 1.6-3.4; p < 0.001). Mechanical ventilation was necessary for 25.2% of patients with CSVT, of whom the majority were neonates and young children. The need for mechanical ventilation was associated with increased mortality (OR 16.6; 95% CI 9.9-27.9; p < 0.001). The overall mortality rate for CSVT was 4.1%, and 16.5% of patients with CSVT were discharged with home health care or to a skilled nursing facility. CONCLUSIONS: CSVT, which has a U-shaped age distribution, is an uncommon condition in children. Stroke is common in children with CSVT, and it is associated with an increased need for mechanical ventilation and increased mortality. The need for mechanical ventilation is more common in infants, and it is associated with increased mortality across all age groups.

Epidemiology and Clinical Features of Human Metapneumovirus and Respiratory Syncytial Viral Infections in Children.

BACKGROUND: Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are 2 common causes of acute respiratory tract infections in infants and young children. The objective of this study is to compare the demographics and outcomes of children hospitalized with HMPV and RSV infections in the United States. METHODS: We performed a retrospective cohort analysis of children 1 month to less than 3 years old discharged during 2016 with HMPV or RSV infection using the Kids' Inpatient Database. Children with HMPV and RSV coinfection were excluded. Data were weighted for national estimates. RESULTS: There were 6585 children with HMPV infection and 70,824 with RSV infection discharged during the study period. The mean age of children with HMPV infection was higher than that of children with RSV infection (0.73 ± 0.8 vs. 0.42 ± 0.7 years; P < 0.05). The mortality rate was significantly higher in children with the presence of any complex chronic conditions compared to those without, in both HMPV [odds ratio (OR): 32.42; CI: 9.931-105.857; P < 0.05] as well as RSV (OR: 35.81; CI: 21.12-57.97; P < 0.05) groups. The adjusted median length of stay was longer (4.64 days; CI: 4.52-4.76 days vs. 3.33 days; CI: 3.31-3.35 days; P < 0.001) and total charges were higher ($44,358; CI: $42,145-$46,570 vs. $22,839; CI: $22,512-$23,166; P < 0.001), with HMPV infection. The mortality rate was similar in HMPV infection compared to RSV infection on multivariable analysis (OR: 1.48; P > 0.05). CONCLUSION: In hospitalized children in the United States, HMPV infection is less common than RSV infection. Complex chronic conditions are more prevalent in children hospitalized with HMPV infection. Hospitalization with HMPV is associated with longer length of stay and higher hospital charges. The adjusted mortality is similar with both infections.

Identification of Multisystem Inflammatory Syndrome in Children Classes and Development of Hyperinflammation Score in Pediatric COVID-19.

The aim of this study is to describe characteristics and hospital course of children admitted with COVID-19 to a tertiary care pediatric center in Southeastern United States, and to present the frequency of three classes of multisystem inflammatory syndrome in children (MIS-C) and develop pediatric COVID-19 associated hyperinflammation score (PcHIS). A retrospective cohort study of 68 children was performed. Critical illness was defined as any child requiring respiratory or cardiovascular support or renal replacement therapy. PcHIS was developed by using six variables: fever, hematological dysfunction, coagulopathy, hepatic injury, macrophage activation, and cytokinemia. Centers for Disease Control and Prevention criteria were used to identify MIS-C, and three classes of MIS-C were identified based on the findings of recently published latent class analysis (Class 1: MIS-C without Kawasaki like disease, Class 2: MIS-C with respiratory disease, and Class 3: MIS-C with Kawasaki like disease). The median age was 6.4 years. Fever, respiratory, and gastrointestinal were common presenting symptoms. MIS-C was present in 32 (47%), critical COVID-19 illness in 11 (16%), and 17 (25%) were admitted to the PICU. Children with critical illness were adolescents with elevated body mass index and premorbid conditions. PcHIS score of 3 had a sensitivity of 100% and a specificity of 77% for predicting critical COVID-19 illness. Among MIS-C patients, 15 (47%) were in Class 1, 8 (25%) were in Class 2, and 9 (28%) were in Class 3. We conclude that most children with COVID-19 have mild-to-moderate illness. Critical COVID-19 is mainly seen in obese adolescents with premorbid conditions. Three Classes of MIS-C are identifiable based on clinical features. Validation and clinical implication of inflammation score in pediatric COVID-19 need further investigation.

Coronavirus Disease 2019 in Pediatric Oncology Patients: A Matched-Cohort Analysis of the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry.

BACKGROUND: There is a paucity of multicenter data describing the impact of coronavirus disease 2019 (COVID-19) on hospitalized pediatric oncology patients. Using a large, multicenter, Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness University Study (VIRUS) database, we aimed at assessing outcomes of COVID-19 infection in this population. METHOD: This is a matched-cohort study involving children below 18 years of age hospitalized with COVID-19 between March 2020 and January 2021. Using the VIRUS; COVID-19 Registry database, children with oncologic diseases were compared with propensity score matched (age groups, sex, race, and ethnicity) cohort of children without oncologic diseases for the prevalence of Multisystem Inflammatory Syndrome in Children (MIS-C), intensive care unit (ICU) admission, interventions, hospital, and ICU length of stay. RESULTS: The number of children in the case and control groups was 45 and 180, respectively. ICU admission rate was similar in both groups ([47.7 vs 51.7%], P =0.63). The proportion of children requiring noninvasive and invasive mechanical ventilation, and its duration were similar between groups, same as hospital mortality. Interestingly, MIS-C was significantly lower in the oncology group compared with the control (2.4 vs 24.6%; P =0.0002). CONCLUSIONS: In this study using a multicenter VIRUS database, ICU admission rate, interventions, and outcomes of COVID-19 were similar in children with the oncologic disease compared with control patients. The incidence of MIS-C is lower in oncologic patients.

The need for blood transfusion therapy is associated with increased mortality in children with traumatic brain injury.

OBJECTIVE: Blood transfusion therapy (BTT) is widely used in trauma patients. However, the adverse effects of BTT in pediatric trauma patients with traumatic brain injury (TBI) were poorly studied. The objective of this study is to evaluate the effect of BTT on mortality in children with severe TBI. METHODS: In this retrospective cohort analysis, we analyzed 2012 and 2016 Kids' Inpatient Databases and used a weighted sample to obtain national outcome estimates. We included children aged 1 month to 21 years with TBI who were mechanically ventilated, considered severe TBI; we then compared the demographics, comorbidities, and mortality rates of those patients who had undergone BTT to those who did not. Statistical analysis was performed using the chi-squared test and regression models. In addition, in a correlative propensity score matched analysis, cases (BTT) were matched 1:1 with controls (non-BTT) based on age, gender, hospital region, income quartiles, race, and All Patients Refined Diagnosis Related Groups (APRDRG) severity of illness scores to minimize the effect of confounding variables between the groups. RESULTS: Out of 87,980 children with a diagnosis of TBI, 17,199 (19.5%) with severe TBI were included in the analysis. BTT was documented in 3184 (18.5%) children. Among BTT group, the mortality was higher compared to non-BTT group [31.6% (29.7-33.5%) vs. 14.4 (13.7-15.1%), (OR 2.2, 95% CI 1.9-2.6; p<0.05)]. In the BTT group, infants and adolescents, white race, APRDRG severity of illness, cardiac arrest, platelet, and coagulation factor transfusions were associated with higher mortality. In a propensity-matched analysis, BTT associated with a higher risk of mortality (32.1% [30.1-34.2] vs. 17.4% [15.8-19.1], p<0.05; OR: 2.2, 95% CI: 1.9-2.6). CONCLUSION: In children with severe TBI, blood transfusion therapy is associated with higher mortality.

Management of Anticoagulation during Extracorporeal Membrane Oxygenation in Children.

Extracorporeal Membrane Oxygenation (ECMO) is often used in critically ill children with severe cardiopulmonary failure. Worldwide, about 3600 children are supported by ECMO each year, with an increase of 10% in cases per year. Although anticoagulation is necessary to prevent circuit thrombosis during ECMO support, bleeding and thrombosis are associated with significantly increased mortality risk. In addition, maintaining balanced hemostasis is a challenging task during ECMO support. While heparin is a standard anticoagulation therapy in ECMO, recently, newer anticoagulant agents are also in use. Currently, there is a wide variation in anticoagulation management and diagnostic monitoring in children receiving ECMO. This review intends to describe the pathophysiology of coagulation during ECMO support, review of literature on current and newer anticoagulant agents, and outline various diagnostic tests used for anticoagulation monitoring. We will also discuss knowledge gaps and future areas of research.

The Epidemiology and Outcome of Pericardial Effusion in Hospitalized Children: A National Database Analysis.

OBJECTIVES: To describe the epidemiology of pericardial effusion in hospitalized children and evaluate risk factors associated with the drainage of pericardial effusion and hospital mortality. STUDY DESIGN: A retrospective study of a national pediatric discharge database. RESULTS: We analyzed hospitalized pediatric patients from the neonatal age through 20 years in the Kids' Inpatient Database 2016, extracting the cases of pericardial effusion. Of the 6 266 285 discharged patients recorded, 6417 (0.1%) were diagnosed with pericardial effusion, with the highest prevalence of 2153 patients in teens (13-20 years of age). Pericardial effusion was drained in 792 (12.3%), and the adjusted risk of pericardial drainage was statistically low with rheumatologic diagnosis (OR, 0.485; 95% CI, 0.358-0.657, P < .001). The overall mortality in children with pericardial effusion was 6.8% and 10.9% of those who required pericardial effusion drainage (P < .001). The adjusted risk of mortality was statistically high with solid organ tumor (OR, 1.538; 95% CI, 1.056-2.239, P = .025) and pericardial drainage (OR, 1.430; 95% CI, 1.067-1.915, P = .017) and low in all other age groups compared with neonates, those with cardiac structural diagnosis (OR, 0.322; 95% CI, 0.212-0.489, P < .001), and those with rheumatologic diagnosis (OR, 0.531; 95% CI, 0.334-0.846, P = .008). CONCLUSION: The risk of mortality in hospitalized children with pericardial effusion was higher in younger children with solid organ tumors and those who required pericardial effusion drainage. In contrast, it was lower in older children with cardiac or rheumatologic diagnoses.

Medications and Adherence to Treatment Guidelines Among Children Hospitalized With Acute COVID-19.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) treatment guidelines rapidly evolved during the pandemic. The December 2020 Infectious Diseases Society of America (IDSA) guideline, endorsed by the Pediatric Infectious Diseases Society, recommended steroids for critical disease, and suggested steroids and remdesivir for severe disease. We evaluated how medications for children hospitalized with COVID-19 changed after guideline publication. METHODS: We performed a multicenter, retrospective cohort study of children aged 30 days to <18 years hospitalized with acute COVID-19 at 42 tertiary care US children's hospitals April 2020 to December 2021. We compared medication use before and after the December 2020 IDSA guideline (pre- and postguideline) stratified by COVID-19 disease severity (mild-moderate, severe, critical) with interrupted time series. RESULTS: Among 18 364 patients who met selection criteria, 80.3% were discharged in the postguideline period. Remdesivir and steroid use increased postguideline relative to the preguideline period, although the trend slowed. Postguideline, among patients with severe disease, 75.4% received steroids and 55.2% remdesivir, and in those with critical disease, 82.4% received steroids and 41.4% remdesivir. Compared with preguideline, enoxaparin use increased overall but decreased among patients with critical disease. Postguideline, tocilizumab use increased and hydroxychloroquine, azithromycin, anakinra, and antibiotic use decreased. Antibiotic use remained high in severe (51.7%) and critical disease (81%). CONCLUSIONS: Although utilization of COVID-19 medications changed after December 2020 IDSA guidelines, there was a decline in uptake and incomplete adherence for children with severe and critical disease. Efforts should enhance reliable delivery of guideline-directed therapies to children hospitalized with COVID-19 and assess their effectiveness.

Epidemiology and Outcomes of Neonatal Hemophagocytic Lymphohistiocytosis.

Objectives: Neonatal hemophagocytic lymphohistiocytosis (HLH) is a rare entity. The objective of the study was to describe the prevalence, clinical characteristics, interventions and outcomes of neonates diagnosed with HLH in the United States. Methods: A retrospective analysis of 2009, 2012, and 2016 Kids' Inpatient Database was performed. Neonates discharged/died with a diagnosis of HLH were identified and analyzed. Results: Among 11,130,055 discharges, 76 neonates had a diagnosis of HLH. Fifty-two percent (95% CI: 38.6-63.6) were males and 54% (95% CI: 39.7-68.5) were white. Herpes simplex infection was present in 16% (95% CI: 9.2-28.1). 24.4% (95% CI: 14.5-37.9) received chemotherapy, 11.5% (95% CI: 5.2-23.6) IVIG and 3.6% (95% CI: 0.8-14.4) allogenic hemopoietic stem cell transplantation. Organ dysfunction was commonly seen and severe sepsis was documented in 26.6% (95% CI: 16.4-39.9). Median LOS was 16 (IQR 7-54) days. The mortality was 42% (95% CI: 30.8-55). Conclusions: HLH is a rare diagnosis and carries a high mortality in neonates. Herpes simplex virus is the most common infection associated with neonatal HLH. HLH should be considered in the differential diagnosis in neonates presenting with multi-organ dysfunction or sepsis.

Real-world economic evaluation of prospective rapid whole-genome sequencing compared to a matched retrospective cohort of critically ill pediatric patients in the United States.

There is an increasing demand for supporting the adoption of rapid whole-genome sequencing (rWGS) by demonstrating its real-world value. We aimed to assess the cost-effectiveness of rWGS in critically ill pediatric patients with diseases of unknown cause. Data were collected prospectively of patients admitted to the Nicklaus Children's Hospital's intensive care units from March 2018 to September 2020, with rWGS (N = 65). Comparative data were collected in a matched retrospective cohort with standard diagnostic genetic testing. We determined total costs, diagnostic yield (DY), and incremental cost-effectiveness ratio (ICER) adjusted for selection bias and right censoring. Sensitivity analyses explored the robustness of ICER through bootstrapping. rWGS resulted in a diagnosis in 39.8% while standard testing in 13.5% (p = 0.026). rWGS resulted in a mean saving per person of $100,440 (SE = 26,497, p < 0.001) and a total of $6.53 M for 65 patients. rWGS in critically ill pediatric patients is cost-effective, cost-saving, shortens diagnostic odyssey, and triples the DY of traditional approaches.

The Effect of Electroencephalography Abnormalities on Cerebral Autoregulation in Sedated Ventilated Children.

Purpose: To determine the effects of non-ictal electroencephalogram (EEG) changes on cerebrovascular autoregulation (AR) using the cerebral oximetry index (COx). Materials and Methods: Mean arterial blood pressure (MAP), cerebral tissue oxygenation (CrSO2), and EEG were acquired for 96 h. From all of the EEG recordings, 30 min recording segments were extracted using the endotracheal suction events as the guide. EEG recordings were classified as EEG normal and EEG abnormal groups. Each 30 min segment was further divided into six 5 min epochs. Continuous recordings of MAP and CrSO2 by near-infrared spectroscopy (NIRS) were extracted. The COx value was defined as the concordance (R) value of the Pearson correlation between MAP and CrSO2 in a 5 min epoch. Then, an Independent-Samples Mann-Whitney U test was used to analyze the number of epochs within the 30 min segments above various R cutoff values (0.2, 0.3, and 0.4) in normal and abnormal EEG groups. A p-value < 0.05 was considered significant, and all analyses were two-tailed. Results: Among 16 sedated, mechanically ventilated children, 382 EEG recordings of 30 min segments were analyzed. The proportions of epochs in each 30 min segment above the R cutoff values were similar between the EEG normal and EEG abnormal groups (p > 0.05). The median concordance values for CSrO2 and MAP in EEG normal and EEG abnormal groups were similar (0.26 (0.17−0.35) and 0.18 (0.12−0.31); p = 0.09). Conclusions: Abnormal EEG patterns without ictal changes do not affect cerebrovascular autoregulation in sedated and mechanically ventilated children.

A Case of a Lethal Diquat Ingestion in a Toddler.

BACKGROUND: Diquat is an herbicide that may cause rapid and profound systemic toxicity. It can cause multisystem organ failure, primarily via its effects on the gastrointestinal, renal, cardiovascular, and central nervous systems. Case fatality rates as high as 43% have been reported. There is a paucity of pediatric literature on diquat poisoning, and in this article, we will discuss an unfortunate pediatric case that highlights the severity of diquat toxicity. CASE REPORT: We present the case of a child who ingested diquat, which led to multisystem organ failure and death. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians should be aware of this herbicide's potential for significant morbidity and mortality, especially in children, in whom small quantities can be lethal. It is important that emergency physicians are aware of the significant toxicity of diquat and provide early gastric decontamination, as it is the only proven therapeutic strategy.

Characteristics and Outcomes of Children With Necrotizing Pneumonia.

OBJECTIVES: In this study, we describe the characteristics and outcomes of pediatric necrotizing pneumonia in the United States. DESIGN AND SETTING: A retrospective analysis of the Healthcare Cost and Utilization Project 2016 Kids Inpatient Database was performed. The Kids Inpatient Database is a large deidentified hospital discharge database of pediatric patients in the United States. PATIENTS: The database was filtered using International Classification of Diseases, 10th Edition code J85.0 to identify necrotizing pneumonia in children 28 days to 20 years old. INTERVENTIONS: Children with necrotizing pneumonia with and without bacterial isolation and with and without complex chronic conditions were compared. Sample weighting was employed to produce national estimates. MEASUREMENTS AND MAIN RESULTS: Of the 2,296,220 discharges, 746 patients had necrotizing pneumonia (prevalence: 3.2/10,000 discharges). In patients with necrotizing pneumonia, 46.6% required chest tubes, 6.1% underwent video-assisted thoracoscopic surgery, and 27.6% were mechanically ventilated. Pneumothorax was identified in 16.7% and pyothorax in 27.4%. The overall mortality rate was 4.1% (n = 31). Bacterial isolation was documented in 40.9%. The leading organisms identified in patients without a complex chronic condition were Streptococcus pneumoniae (12.6%) and Staphylococcus aureus (9.2%) and in patients with a complex chronic condition were S. aureus (13.4%) and Pseudomonas aeruginosa (12.8%). Patients with bacterial isolation were significantly more likely to develop pneumothorax (odds ratio, 2.6; CI, 1.6-4.2) or septic shock (odds ratio, 3.2; CI, 1.9-5.4) and require a chest tube (odds ratio, 2.5; CI, 1.7-3.5) or mechanical ventilation (odds ratio, 2.3; CI, 1.5-3.3) than patients without bacterial isolation. CONCLUSIONS: Bacterial etiology of necrotizing pneumonia in children varied with the presence or absence of a complex chronic condition. Bacterial isolation is associated with increased invasive procedures and complications. The mortality rate is higher in children with complex chronic conditions. This study provides national data on necrotizing pneumonia among hospitalized children.