Recruitment and retention of pediatric participants for pandemic preparedness research: Experience from the PREMISE EV-D68 Pilot Study.

Recruitment and retention are challenges for prospective pediatric cohort studies, particularly those involving serial venipunctures. We investigated factors underlying enrollment and retention in the Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) Enterovirus D68 (EV-D68) Pilot Study, a multicenter prospective longitudinal cohort study assessing the utility of immunologic surveillance for pandemic preparedness. This study enrolls children ≤10 years for two blood draws, pre- and post-EV-D68 season, separated by 6-18 months. Overall, 174 children were enrolled in Cohort 1 of the study and 120 (69 %) of children completed the study, with follow-up blood samples obtained from 101 (58 %) of participants. Families were primarily motivated to participate by a desire to help other children, advance science, and better prepare for the next pandemic. Adding research blood draws to clinically indicated blood draws improved enrollment, and multiple study touch points facilitated retention. These findings can be applied to improve recruitment and retention in future pandemic preparedness efforts and longitudinal pediatric cohort studies.

Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US.

Recent outbreaks of enterovirus D68 (EV-D68) infections, and their causal linkage with acute flaccid myelitis (AFM), continue to pose a serious public health concern. During 2020 and 2021, the dynamics of EV-D68 and other pathogens have been significantly perturbed by non-pharmaceutical interventions against COVID-19; this perturbation presents a powerful natural experiment for exploring the dynamics of these endemic infections. In this study, we analyzed publicly available data on EV-D68 infections, originally collected through the New Vaccine Surveillance Network, to predict their short- and long-term dynamics following the COVID-19 interventions. Although long-term predictions are sensitive to our assumptions about underlying dynamics and changes in contact rates during the NPI periods, the likelihood of a large outbreak in 2023 appears to be low. Comprehensive surveillance data are needed to accurately characterize future dynamics of EV-D68. The limited incidence of AFM cases in 2022, despite large EV-D68 outbreaks, poses further questions for the timing of the next AFM outbreaks.

Inpatient and Outpatient Differences in Pediatric Patients with Laboratory-confirmed COVID-19.

Among 30,286 pediatric inpatient and outpatient encounters with laboratory-confirmed COVID-19 seen at one of 40 US healthcare organizations, 1586 (5.2%) were inpatient. Encounter types varied by age and sex; the proportion of Black/African American inpatients was significantly higher than outpatients, and Hispanic/Latinx children made up nearly one-fourth of patients.

Streptococcal Pharyngitis: Compliance With National Testing Guidelines in a Pediatric Emergency Department.

OBJECTIVES: The Infectious Diseases Society of America (IDSA) guidelines regarding group A streptococcal (GAS) pharyngitis advise against routine testing for patients younger than 3 years, patients without pharyngitis, and patients with symptoms suggesting a viral infection. Group A streptococcal testing may be overused in some clinical settings; thus, we conducted this study to evaluate compliance with the IDSA guidelines in a pediatric emergency department (ED) setting. METHODS: This retrospective cohort study describes patients younger than 18 years presenting to 2 urban pediatric EDs in 2016 who underwent rapid antigen detection testing for GAS pharyngitis. Testing was classified as noncompliant with the IDSA guidelines if the chief complaint was not indicative of GAS infection and/or the patient age was younger than 3 years. Appropriate nonparametric tests compared groups by IDSA testing compliance status. RESULTS: A total of 13,585 patient encounters met inclusion criteria; 5255 (39%) were noncompliant with the IDSA testing guidelines, the majority due to a chief complaint inconsistent with GAS pharyngitis (67%) and secondarily due to the age of younger than 3 years (48%). Among the patients with noncompliant testing, 51% were prescribed an antibiotic, and return encounters were more likely to occur (13% vs 10%, P < 0.001). Return encounters more commonly resulted in respiratory diagnoses in those with noncompliant GAS testing (60% vs 45%, P < 0.001). CONCLUSIONS: Nearly 40% of all pediatric ED encounters with GAS testing were noncompliant with the IDSA guidelines and were associated with greater return encounter rates. Potential negative outcomes from noncompliant GAS testing include misdiagnosis, inappropriate use of antibiotics, allergic reactions, and loss of school days. Informed interventions to reduce unnecessary GAS testing are warranted.

Factors Associated With COVID-19 Disease Severity in US Children and Adolescents.

BACKGROUND: Little is known about the clinical factors associated with COVID-19 disease severity in children and adolescents. METHODS: We conducted a retrospective cohort study across 45 US children's hospitals between April 2020 to September 2020 of pediatric patients discharged with a primary diagnosis of COVID-19. We assessed factors associated with hospitalization and factors associated with clinical severity (eg, admission to inpatient floor, admission to intensive care unit [ICU], admission to ICU with mechanical ventilation, shock, death) among those hospitalized. RESULTS: Among 19,976 COVID-19 encounters, 15,913 (79.7%) patients were discharged from the emergency department (ED) and 4063 (20.3%) were hospitalized. The clinical severity distribution among those hospitalized was moderate (3222, 79.3%), severe (431, 11.3%), and very severe (380, 9.4%). Factors associated with hospitalization vs discharge from the ED included private payor insurance (adjusted odds ratio [aOR],1.16; 95% CI, 1.1-1.3), obesity/type 2 diabetes mellitus (type 2 DM) (aOR, 10.4; 95% CI, 8.9-13.3), asthma (aOR, 1.4; 95% CI, 1.3-1.6), cardiovascular disease, (aOR, 5.0; 95% CI, 4.3- 5.8), immunocompromised condition (aOR, 5.9; 95% CI, 5.0-6.7), pulmonary disease (aOR, 5.3; 95% CI, 3.4-8.2), and neurologic disease (aOR, 3.2; 95% CI, 2.7-5.8). Among children and adolescents hospitalized with COVID-19, greater disease severity was associated with Black or other non-White race; age greater than 4 years; and obesity/type 2 DM, cardiovascular, neuromuscular, and pulmonary conditions. CONCLUSIONS: Among children and adolescents presenting to US children's hospital EDs with COVID-19, 20% were hospitalized; of these, 21% received care in the ICU. Older children and adolescents had a lower risk for hospitalization but more severe illness when hospitalized. There were differences in disease severity by race and ethnicity and the presence of selected comorbidities. These factors should be taken into consideration when prioritizing mitigation and vaccination strategies.

Trends in Pediatric Viral Symptoms, Influenza Testing, and SARS-CoV-2 Testing From a Statewide Electronic Health Record Consortium, January 2017 to July 2021.

OBJECTIVE: The heterogeneous implementation and uptake of nonpharmaceutical interventions (NPIs) during the coronavirus disease 2019 (COVID-19) pandemic amplified the need for locally responsive disease surveillance mechanisms. Using data from a newly developed statewide electronic health record (EHR) consortium in Minnesota, we sought to characterize trends in pediatric viral symptoms, influenza testing, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. METHODS: We conducted a serial cross-sectional analysis of EHR data from 1/1/2017 to 7/30/2021 across 8 large health systems in Minnesota. We included patients ≤18 years of age with any SARS-CoV-2 test, influenza test, or documented diagnostic code which met our viral symptom definition. We plotted week-by-week trends in viral symptoms, SARS-CoV-2 and influenza testing, and test positivity, stratified between children (0-11 years) and adolescents (12-18 years). RESULTS: We identified 1,079,924 patients ≤18 years of age with viral symptoms or testing; 880,669 (81.5%) were children ≤11 years. Influenza testing and influenza test positivity remained well below historical averages from March 2020 through mid-May 2021. Peaks in viral symptoms during this time were concomitant with peaks in SARS-CoV-2 testing and test positivity, whereas influenza testing and test positivity remained stagnant. Influenza test positivity rates increased substantively among children from May through July 2021. CONCLUSIONS: Viral illness and influenza testing among pediatric patients were below historical averages throughout the COVID-19 pandemic. Ongoing increases in influenza test positivity may merit clinical and public health awareness and intervention. Future NPI policies can be better targeted with insights from collaborative EHR-based surveillance, which enhances real-time, locally sensitive measurement of disease outbreaks.

Association Between Caseload Surge and COVID-19 Survival in 558 U.S. Hospitals, March to August 2020.

BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload. LIMITATION: Residual confounding. CONCLUSION: Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute.

The COVID-19 Pandemic and Changes in Healthcare Utilization for Pediatric Respiratory and Nonrespiratory Illnesses in the United States.

The impact of COVID-19 public health interventions on pediatric illnesses nationwide is unknown. We performed a multicenter, cross-sectional study of encounters at 44 children's hospitals in the United States to assess changes in healthcare utilization during the pandemic. The COVID-19 pandemic was associated with substantial reductions in encounters for respiratory diseases; these large reductions were consistent across illness subgroups. Although encounters for nonrespiratory diseases decreased as well, reductions were more modest and varied by age. Encounters for respiratory diseases among adolescents declined to a lesser degree and returned to previous levels faster compared with those of younger children. Further study is needed to determine the contributions of decreased illness and changes in care-seeking behavior to this observed reduction.

Organ Donation Authorization After Brain Death Among Patients Admitted to PICUs in the United States, 2009-2018.

OBJECTIVES: To identify trends in and factors associated with pediatric organ donation authorization after brain death. DESIGN: Retrospective cohort study of data from Virtual Pediatric Systems, LLC (Los Angeles, CA). SETTING: Data from 123 PICUs reporting to Virtual Pediatric Systems from 2009 to 2018. PATIENTS: Patients less than 19 years old eligible for organ donation after brain death. MEASUREMENTS AND MAIN RESULTS: Of 2,777 eligible patients, 1,935 (70%) were authorized for organ donation; the authorization rate remained unchanged over time (ptrend = 0.22). In a multivariable logistic regression model, hospitalizations lasting greater than 7 days had lower odds of authorization (adjusted odds ratio, 0.5; p < 0.001 vs ≤ 1 d) and White patients had higher odds than other race/ethnicity groups. Authorization was higher for trauma-related encounters (adjusted odds ratio, 1.5; p < 0.001) and when donation was discussed with an organ procurement organization coordinator (adjusted odds ratio, 1.7; p < 0.001). Of 123 hospitals, 35 (28%) met or exceeded a 75% organ donation authorization target threshold; these hospitals more often had an organ procurement organization coordinator discussing organ donation (85% vs 72% of encounters; p < 0.001), but no difference was observed by PICU bed size. CONCLUSIONS: Organ donation authorization after brain death among PICU patients was associated with length of stay, race/ethnicity, and trauma-related encounter, and authorization rates were higher when an organ procurement organization coordinator was involved in the donation discussion. This study identified factors that could inform initiatives to improve the authorization process and increase pediatric organ donation rates.

Developing algorithms for identifying major structural birth defects using automated electronic health data.

PURPOSE: Given the 2015 transition to International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic coding, updates to our previously published algorithms for major structural birth defects (BDs) were necessary. Aims of this study were to update, validate, and refine algorithms for identifying selected BDs, and then to use these algorithms to describe BD prevalence in the vaccine safety datalink (VSD) population. METHODS: We converted our ICD-9-CM list of selected BDs to ICD-10-CM using available crosswalks with manual review of codes. We identified, chart reviewed, and adjudicated a sample of infants in the VSD with ≥2 ICD-10-CM diagnoses for one of seven common BDs. Positive predictive values (PPVs) were calculated; for BDs with suboptimal PPV, algorithms were refined. Final automated algorithms were applied to a cohort of live births delivered 10/1/2015-9/30/2017 at eight VSD sites to estimate BD prevalence. This research was approved by the HealthPartners Institutional Review Board, by all participating VSD sites, and by the CDC, with a waiver of informed consent. RESULTS: Of 573 infants with ≥2 diagnoses for a targeted BD, on adjudication, we classified 399 (69.6%) as probable cases, 31 (5.4%) as possible cases and 143 (25.0%) as not having the targeted BD. PPVs for the final BD algorithms ranged from 0.76 (hypospadias) to 1.0 (gastroschisis). Among 212 857 births over 2 years following transition to ICD-10-CM coding, prevalence for the full list of selected defects in the VSD was 1.8%. CONCLUSIONS: Algorithms can identify infants with selected BDs using automated healthcare data with reasonable accuracy. Our updated algorithms can be used in observational studies of maternal vaccine safety and may be adapted for use in other surveillance systems.

Emergency Department Visits for Pediatric Firearm Injuries by Trauma Center Type.

OBJECTIVES: This study aimed to characterize pediatric visits to emergency departments (EDs) for firearm injuries and examine differences by trauma center type. METHODS: Analyses included all patients younger than 19 years from the National Trauma Data Bank, years 2009 to 2014. Trauma centers were categorized as adult, mixed adult and pediatric, or pediatric based on certification level. Baseline characteristics were compared between subgroups using χ2 tests. Multivariable logistic regression was used to examine risk of death. RESULTS: Of 466,403 pediatric ED visits, 21,416 (4.6%) resulted from a firearm injury. Most firearm injuries were treated at an adult (64.9%) or mixed trauma center (29.1%) and involved patients that were male (87.1%), in the 15- to 18-year age group (83.2%), and black or African American (61.3%). Most visits were for injuries resulting from assault (78.1%), followed by unintentional (12.6%) and self-inflicted (4.7%) injuries, undetermined intent (3.7%), and legal intervention (0.8%). Patients visiting EDs for firearm injuries had more than 7 times the odds of dying compared with patients with other injuries (odds ratio, 7.30; 95% confidence interval, 6.82-7.72), and firearm injuries were responsible for more than a quarter (26.1%) of the total pediatric deaths in the National Trauma Data Bank (n = 2866). Assault-related injuries resulted in the most deaths (n = 2010; 70.1%), but the case fatality rate was highest for self-inflicted (n = 453; 44.6%). CONCLUSION: We identified more than 20,000 firearm-related ED visits by pediatric patients from 2009 to 2014, averaging nearly 10 visits per day. Findings from this study can inform strategic planning in hospitals focused on preventing firearm injuries in children and adolescents.

Epidemiology of Serratia Bloodstream Infections Among Hospitalized Children in the United States, 2009-2016.

Serratia can cause serious bloodstream infections (BSIs). This retrospective cohort study identified 5,312 pediatric inpatient encounters with BSIs from 2009 to 2016, of which 82 (0.01%) had Serratia BSIs. The rate among hospitalized patients increased significantly from 0.4 in 2009 to 1.0 in 2016 per 10,000 admissions. Risk factors differed and outcomes were worse for Serratia BSIs compared with non-Serratia BSIs.

Low Use of Vitamin A in Children Hospitalized for Measles in the United States.

Vitamin A reduces measles morbidity/mortality and and is recommended for management. We studied 142 patients hospitalized at US Children's hospitals for measles between January 1, 2004, and March 31, 2019, and found only 47 (33%) received vitamin A. Patients with complex chronic conditions were less likely to be treated. This study highlights a concerning gap between recommendations and practice for hospital management of measles.

Correction to: Sleep-disordered breathing: an under-recognized problem in infants with myelomeningocele defects regardless of timing of repair.

Since the online publication of this article, the authors have noted an error in Table 1. The correct table is provided. The authors apologise for any inconvenience caused.

Sleep-disordered breathing: an under-recognized problem in infants with myelomeningocele defects regardless of timing of repair.

OBJECTIVE: To evaluate the prevalence of sleep-disordered breathing (SDB) in infants with myelomeningocele (MMC) and the effect of fetal repair on SDB. STUDY DESIGN: We conducted a retrospective cohort study of infants with MMC admitted to a pediatric hospital (2007-2017). Pneumocardiogram (PCG) results, a measure of SDB, were compared between infants who underwent fetal MMC (fMMC) versus postnatal MMC repair. RESULT: Of 118 eligible infants, 17 (14%) underwent fetal repair. Of these, 106 (90%) had PCG studies; abnormal PCG results were common but not different between fMMC (n = 12, 92%) and postnatal repair groups (n = 72, 77%, p = 0.22). Among infants with abnormal results, central apnea events >10 s (median 16 vs. 3 events, p = 0.02) and percentage of time spent in periodic breathing (median 15% vs. 7%, p = 0.01) were greater in the fMMC group. CONCLUSION: SDB was common among all MMC infants regardless of repair timing, indicating a need for standard screening recommendations.

ZAP-VAP: A Quality Improvement Initiative to Decrease Ventilator-Associated Pneumonia in the Neonatal Intensive Care Unit, 2012-2016.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the second most frequent hospital-acquired infection in neonatal intensive care units (NICUs) and significantly affects neonatal morbidity and mortality. The population most at risk for VAP are extremely preterm infants. PURPOSE: The objectives of this quality improvement project were to create and evaluate the effectiveness of a VAP prevention bundle ("ZAP-VAP") in reducing VAP. METHODS: The development of the ZAP-VAP bundle and creation of audit tools were documented. A targeted gestational age less than 29 weeks was selected for this study. Electronic medical record review was used to determine the preintervention baseline for patient outcomes. Patient medical record data were analyzed retrospectively to measure patient outcomes preimplementation. VAP rates (number of VAP cases per 1000 ventilator days) were calculated pre- and postintervention. After implementation, data were analyzed prospectively to measure patient outcomes between neonates who developed VAP and those who did not. RESULTS: The VAP rate significantly decreased from 8.5 (2010-2011) to 2.5 (P= .0004) postintervention (2016). Median mechanical ventilation days decreased among VAP cases (47 vs 33 days) and slightly increased among non-VAP cases (19 vs 24 days) during the intervention period. Median length of stay decreased for VAP cases (136 vs 100 days) but remained unchanged for non-VAP cases (85 vs 84 days). IMPLICATIONS FOR PRACTICE: The intervention was implemented from 2012 to 2016. The protocol was readily accepted by our neonatal intensive care unit (NICU) team through education and practice changes. ZAP-VAP is an effective and straightforward protocol that improved VAP outcomes in our level IIIB NICU. An interdisciplinary team successfully implemented this intervention for mechanically ventilated infants of all gestational ages in our unit and has been a model for these practice changes in other units and other hospitals. IMPLICATIONS FOR RESEARCH: Future studies should focus on how to create sustainable interventions to decrease VAP in NICUs and to expand the approaches to other units in our hospital and other hospitals in our city among patients at risk for VAP.

Demographics, Complications and Resource Utilization for Patients Hospitalized for Measles Across Us Children's Hospitals.

Our objective was to retrospectively describe measles hospitalizations in 52 US children's hospitals. We identified 136 patients hospitalized for measles in 2004-2018; 17% (23/136) had complex chronic conditions, 2 of whom died or were in hospice. Among noncomplex patients only 39% received vitamin A, median length of stay was 3 days and median adjusted estimated costs were $5896.

Measles Hospitalizations at a United States Children's Hospital 2011-2017.

BACKGROUND: There are no recent descriptions of measles hospitalizations and complications in US children despite outbreaks within the past decade-including 2 in Minnesota (2011 and 2017). The objective of our study was to describe complications, hospital management and resource utilization for children hospitalized for measles at a US children's hospital. METHODS: Retrospective case series of children (0-18 years of age) hospitalized for measles (observation/inpatient diagnosis code for measles) at Children's Minnesota, January 1, 2011, to September 1, 2017. Descriptive statistics were performed. RESULTS: Thirty-three patients were included (7 from 2011 and 21 from 2017 outbreaks). Median age was 27 months (range, 6-95 months), 94% were Black or African American (73% Somali ethnicity), 88% had medical assistance and 91% were unvaccinated to measles. Poor feeding was a primary reason for admission (97%); additional complications included otitis media (42%), pneumonia (30%), tracheitis (6%) and keratitis (3%). Additional testing was common [chest radiographs (70%), blood cultures (64%), nonmeasles viral testing (42%)]. Seventy-three percent received antibiotics, 30% required oxygen and 21% received vitamin A. Median length of stay was 3.7 days (range, 1.1-26.2 days); 1 patient was readmitted. Median direct cost in 2017 was $5291 (interquartile range : $3907-$7519), and estimated total cost to the hospital for the 2017 outbreak was $1.3 million. CONCLUSIONS: Clinicians should be aware of measles complications and treatment. Public and private health efforts should continue to focus on immunization, given significant implications of measles infections for patients and healthcare systems. Future studies may assess complications of measles across the United States as individual outbreaks often occur in specific populations, making generalization of results challenging.