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 aged 29 days to 17 years 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.

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.

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.

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.

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.

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.

Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry.

OBJECTIVES: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. DESIGN: Retrospective study. SETTING: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. PATIENTS: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. CONCLUSIONS: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

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.

Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections.

BACKGROUND: Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management and in characterizing prognosis. Usual care testing by culture and polymerase chain reaction is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with central nervous system (CNS) infections. METHODS: We conducted a prospective multisite study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to 1 of 3 tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis. RESULTS: We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. Metagenomic next-generation sequencing of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours. CONCLUSIONS: Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.

Pediatric COVID-19 presenting as supraglottitis with vocal cord hypomobility.

In the United States, an estimated 7.3% of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) are among persons aged less than 18 years. Data regarding clinical manifestations in this age group are still evolving. An upper airway predilection has been reported in children. We describe the case of a 15-year-old female with supraglottitis and unilateral hypomobility of vocal cord with concern for critical airway, associated with COVID-19. She was managed by a multidisciplinary team including critical care, infectious diseases, and otolaryngology. This report adds to the sparse but evolving body of literature on the clinical presentation of COVID-19 disease in children.

The need for hemodialysis is associated with increased mortality in mechanically ventilated children: a propensity score-matched outcome study.

BACKGROUND: Kidney replacement therapy (KRT) is frequently used in critically ill children. The objective of this study is to investigate if the requirement for hemodialysis (HD) is an independent risk factor for mortality in mechanically ventilated children METHODS: In this retrospective cohort study, we analyzed the 2012 and 2016 Kids Inpatient Database and used a weighted sample to obtain a national outcome estimate. For our analysis, we included children aged one month to 17 years who were mechanically ventilated; we then compared the demographics, comorbidities, and mortality rates of those patients who had undergone HD with those who did not. Statistical analysis was performed using the chi-squared test and regression models. The patients were matched 1:2 with a correlative propensity score using age, weekend admission, elective admission, gender, hospital region, income quartiles, race, presence of kidney failure, bone marrow transplantation (BMT), cardiac surgery, trauma, and All Patients Refined Diagnosis Related Groups (APR-DRG) severity score. The mortality rate was compared between the matched groups. RESULTS: Out of 100,289 mechanically ventilated children, 1393 (1.4%) underwent HD. The mortality rate was 32.5% in the HD group, compared with 8.8% in the control group (p < 0.05). Factors that were associated with higher mortality in HD patients included severe sepsis, BMT, cardiopulmonary resuscitation (CPR), and extracorporeal membrane oxygenation therapy (ECMO). After propensity score-matched analysis, HD was still significantly associated with a higher risk of mortality (31.9% vs. 22.0%, p < 0.05) CONCLUSIONS: The requirement for HD in mechanically ventilated children is associated with higher mortality.

Takotsubo cardiomyopathy in children.

OBJECTIVE: To explore the epidemiology and outcomes of takotsubo cardiomyopathy in children. METHODS: A retrospective analysis of the Healthcare Cost and Utilization 2012 and 2016 Kids' Inpatient Database was performed. Patients admitted with the diagnosis of takotsubo cardiomyopathy in the age group of 1 month-20 years were identified using International Classification of Diseases (ICD)-9 code 429.83 and ICD-10 code I51.81. RESULTS: Among a total of 4,860,859 discharges, there were 153 with the diagnosis of takotsubo cardiomyopathy (3.1 per 100,000 discharges). Among patients with takotsubo cardiomyopathy, 55.0% were male, 62.4% were white, and 16.7% were black. Eighty-nine percent of patients were between 12 and 20 years. Psychiatric diagnosis was documented in 46% and substance use disorder in 36.2%. Sepsis was documented in 22.8% of patients. The median length of stay was 5 days (interquartile range: 2.7-15), and median total charges were $75,080 (interquartile range: 32,176-198,336). The overall mortality for takotsubo cardiomyopathy was 7%. On multivariable regression analysis, mortality was higher in the presence of anoxic injury (odds ratio = 34.42, 95% confidence interval: 4.85-320.11, p = 0.00). CONCLUSIONS: Takotsubo cardiomyopathy is uncommon in children and carries a mortality rate of 7%. Most children with takotsubo cardiomyopathy are adolescent males, many of whom have psychiatric disorder or substance use disorder or both. Takotsubo cardiomyopathy should be considered in the differential diagnosis for patients who present with cardiac dysfunction and have underlying psychiatric disorders or drug abuse.

Course and Outcome of Children with Convulsive Status Epilepticus Admitted to a Pediatric Intensive Care Unit.

Introduction The objective of this study was to describe the course and the outcomes of children with convulsive status epilepticus and to evaluate the differences between two groups of children with new-onset seizures and known seizure disorders. Methods This is a retrospective, single-center study. Children with convulsive status epilepticus admitted to our tertiary care pediatric intensive care unit were included in the study. Medical records were reviewed to obtain the demographic- and seizure-related variables. Results Among 139 children with status epilepticus, 69.7% (n = 99) had a known seizure disorder. Focal seizures were present in 23.9% of children, and 34.6% required intubation; there was an overall mortality rate of 1.2%. The children with new-onset seizures were younger and received electroencephalography (EEG) and neuroimaging more often compared to children with known seizure disorders (p < 0.05). However, an abnormal EEG was more common among children with known seizure disorders (p < 0.001). Conclusions Sub-therapeutic anti-epileptic drugs levels were common among children with known seizure disorders presenting with status epilepticus. Gender, race, insurance status, type of seizures, intubation requirement, lengths of stay, and mortality were not significantly different between the two groups.