Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

A genetically modulated Toll-like-receptor-tolerant phenotype in peripheral blood cells of children with multisystem inflammatory syndrome.

Dysregulated innate immune responses contribute to multisystem inflammatory syndrome in children (MIS-C), characterized by gastrointestinal, mucocutaneous, and/or cardiovascular injury occurring weeks after SARS-CoV-2 exposure. To investigate innate immune functions in MIS-C, we stimulated ex vivo peripheral blood cells from MIS-C patients with agonists of Toll-like receptors (TLR), key innate immune response initiators. We found severely dampened cytokine responses and elevated gene expression of negative regulators of TLR signaling. Increased plasma levels of zonulin, a gut leakage marker, were also detected. These effects were also observed in children enrolled months after MIS-C recovery. Moreover, cells from MIS-C children carrying rare genetic variants of lysosomal trafficking regulator (LYST) were less refractory to TLR stimulation and exhibited lysosomal and mitochondrial abnormalities with altered energy metabolism. Our results strongly suggest that MIS-C hyperinflammation and/or excessive or prolonged stimulation with gut-originated TLR ligands drive immune cells to a lasting refractory state. TLR hyporesponsiveness is likely beneficial, as suggested by excess lymphopenia among rare LYST variant carriers. Our findings point to cellular mechanisms underlying TLR hyporesponsiveness; identify genetic determinants that may explain the MIS-C clinical spectrum; suggest potential associations between innate refractory states and long COVID; and highlight the need to monitor long-term consequences of MIS-C.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's RE searching COV ID to E nhance R ecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study ( n =10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. Clinical Trialsgov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.

Child Opportunity Index and Hospital Utilization in Children With Traumatic Brain Injury Admitted to the PICU.

The need to understand how Community-based disparities impact morbidity and mortality in pediatric critical illness, such as traumatic brain injury. Test the hypothesis that ZIP code-based disparities in hospital utilization, including length of stay (LOS) and hospital costs, exist in a cohort of children with traumatic brain injury (TBI) admitted to a PICU using the Child Opportunity Index (COI). DESIGN: Multicenter retrospective cohort study. SETTING: Pediatric Health Information System (PHIS) database. PATIENTS: Children 0-18 years old admitted to a PHIS hospital with a diagnosis of TBI from January 2016 to December 2020 requiring PICU care. To identify the most severely injured children, a study-specific definition of "Complicated TBI" was created based on radiology, pharmacy, and procedure codes. INTERVENTIONS: None. Main Outcomes and Measures: Using nationally normed ZIP code-level COI data, patients were categorized into COI quintiles. A low COI ZIP code has low childhood opportunity based on weighted indicators within educational, health and environmental, and social and economic domains. Population-averaged generalized estimating equation (GEE) models, adjusted for patient and clinical characteristics examined the association between COI and study outcomes, including hospital LOS and accrued hospital costs. The median age of this cohort of 8,055 children was 58 months (interquartile range [IQR], 8-145 mo). There were differences in patient demographics and rates of Complicated TBI between COI levels. The median hospital LOS was 3.0 days (IQR, 2.0-6.0 d) and in population-averaged GEE models, children living in very low COI ZIP codes were expected to have a hospital LOS 10.2% (95% CI, 4.1-16.8%; p = 0.0142) longer than children living in very high COI ZIP codes. For the 11% of children with a Complicated TBI, the relationship between COI and LOS was lost in multivariable models. COI level was not predictive of accrued hospital costs in this study. CONCLUSIONS: Children with TBI requiring PICU care living in low-opportunity ZIP codes have higher injury severity and longer hospital LOS compared with children living in higher-opportunity ZIP codes. Additional studies are needed to understand why these differences exist.

Trends in Disease Severity Among Critically Ill Children With Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Multicenter Cohort Study in the United States.

OBJECTIVES: To describe trends in critical illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children over the course of the COVID-19 pandemic. We hypothesized that PICU admission rates were higher in the Omicron period compared with the original outbreak but that fewer patients needed endotracheal intubation. DESIGN: Retrospective cohort study. SETTING: This study took place in nine U.S. PICUs over 3 weeks in January 2022 (Omicron period) compared with 3 weeks in March 2020 (original period). PATIENTS: Patients less than or equal to 21 years old who screened positive for SARS-CoV-2 infection by polymerase chain reaction or hospital-based rapid antigen test and were admitted to a PICU or intermediate care unit were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 267 patients (239 Omicron and 28 original) were reviewed. Forty-five patients in the Omicron cohort had incidental SARS-CoV-2 and were excluded from analysis. The Omicron cohort patients were younger compared with the original cohort patients (median [interquartile range], 6 yr [1.3-13.3 yr] vs 14 yr [8.3-17.3 yr]; p = 0.001). The Omicron period, compared with the original period, was associated with an average increase in COVID-19-related PICU admissions of 13 patients per institution (95% CI, 6-36; p = 0.008), which represents a seven-fold increase in the absolute number admissions. We failed to identify an association between cohort period (Omicron vs original) and odds of intubation (odds ratio, 0.7; 95% CI, 0.3-1.7). However, we cannot exclude the possibility of up to 70% reduction in intubation. CONCLUSIONS: COVID-19-related PICU admissions were seven times higher in the Omicron wave compared with the original outbreak. We could not exclude the possibility of up to 70% reduction in use of intubation in the Omicron versus original epoch, which may represent differences in PICU/hospital admission policy in the later period, or pattern of disease, or possibly the impact of vaccination.

Examining child flourishing, family resilience, and adversity in the 2016 National Survey of Children's Health.

PURPOSE: Explore factors associated with flourishing and family resilience among children aged 6 months to 5 years old in the 2016 National Survey of Children's Health (NSCH). DESIGN AND METHODS: Cross-sectional analysis of the 2016 NSCH was conducted using Kleinman and Norton's Regression Risk Analysis method to derive adjusted risk measures for logistic regression models to assess factors contributing to (1) child flourishing and (2) child flourishing stratified between resilient and non-resilient families. RESULTS: In multivariable models, resilient families less often reported a child with two or more lifetime ACE exposures (ARD -0.11, 95% CI -0.15, -0.08), more likely to live in a supportive neighborhood (ARD 0.08, 95% CI 0.05,0.11), and more likely to report emotional support in raising children (ARD 0.07, 95% CI 0.12, 0.40). Accounting for ACE exposures, within resilient families, child flourishing was more likely when the child lived in a supportive neighborhood (ARD 0.09, 95% CI 0.03, 0.15), received care in a patient centered medical home (ARD 0.09, 95% CI 0.02,0.15), and when parents reported having emotional support in raising children (ARD 0.10, 95% CI 0.05, 0.17) Within non-resilient families, child flourishing was more likely when parents had emotional support in raising children (ARD 0.15, 95% CI 0.04,0.27). CONCLUSION: Promoting emotional support for parents may bolster family resilience and help young children to flourish despite adversity. PRACTICE IMPLICATIONS: Further research and innovative models of care are needed to optimize the role of pediatric primary care in promoting safe, stable, nurturing relationships and environments for children and families.

Weekend Versus Weekday Asthma-Related Emergency Department Utilization.

OBJECTIVE: To assess variation in asthma-related emergency department (ED) use between weekends and weekdays. METHODS: Cross-sectional administrative claims-based analysis using California 2016 Medicaid data and Vermont 2016 and Massachusetts 2015 all-payer claims databases. We defined ED use as the rate of asthma-related ED visits per 100 child-years. A weekend visit was a visit on Saturday or Sunday, based on date of ED visit claim. We used negative binomial regression and robust standard errors to assess variation between weekend and weekday rates, overall and by age group. RESULTS: We evaluated data from 398,537 patients with asthma. The asthma-related ED visit rate was slightly lower on weekends (weekend: 18.7 [95% confidence interval (CI): 18.3-19.0], weekday: 19.6 [95% CI, 19.3-19.8], P < .001). When stratifying by age group, 3- to 5-year-olds had higher rates of asthma-related ED visits on weekends than weekdays (weekend: 33.7 [95% CI, 32.6-34.7], weekday: 29.8 [95% CI, 29.1-30.5], P < .001) and 12- to 17-year-olds had lower rates of ED visits on weekends than weekdays (weekend: 13.0 [95% CI: 12.5-13.4], weekday: 16.3 [95% CI: 15.9-16.7], P < .001). In the other age groups (6-11, 18-21 years) there were not statistically significant differences between weekend and weekday rates (P > .05). CONCLUSIONS: In this multistate analysis of children with asthma, we found limited overall variation in pediatric asthma-related ED utilization on weekends versus weekdays. These findings suggest that increasing access options during the weekend may not necessarily decrease asthma-related ED use.

Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. Objective: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. Design, Setting, and Participants: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. Exposures: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). Main Outcomes and Measures: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. Results: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). Conclusions and Relevance: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome.

Importance: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures: Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 µg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

Medicaid's EPSDT Benefit: An Opportunity to Improve Pediatric Screening for Social Determinants of Health.

The Early and Periodic Screening, Diagnostic, and Treatment (EPSDT) benefit is a key component of Medicaid policy intended to define an essential set of services provided to patients younger than age 21. Given increasing attention to social determinants of health in pediatric health care, this qualitative review examines the extent to which EPSDT might be used to implement structured screening to identify environmental and social factors affecting children's health. Themes derived from semistructured interviews conducted in 2017 were triangulated with a review of the recent literature to describe how states currently consider the EPSDT benefit with respect to social determinants of health screening. Our findings suggest that, with sufficient stakeholder advocacy given the evidence supporting social determinants of health screening as "medically necessary," EPSDT benefits could be considered as a funding source to incentivize the incorporation of social determinants of health screening into the basic package of well-child care.

Performance of the Person Centered Primary Care Measure in Pediatric Continuity Clinic.

OBJECTIVE: Improvement efforts in pediatric primary care would benefit from measures that capture families' holistic experience of the practice. We sought to assess the reliability and validity of the new Person-Centered Primary Care Measure (PCPCM) in a pediatric resident continuity clinic serving low-income families. METHODS: We incorporated the 11-item PCPCM, stems adapted to reflect a parent responding about their child's visit, into a telephone survey of 194 parents presenting for care in October 2019 at a pediatric resident continuity clinic in Cleveland Ohio (64% response rate). We evaluated PCPCM items using factor analysis and Rasch modeling, and assessed associations of the PCPCM with parents' demographics and perceptions of specific elements of their child's care. RESULTS: In this sample of low-income families, the PCPCM had good reliability (Cronbach's alpha 0.85). All items loaded onto a single factor in principal axes factor analysis. Of the 11 aspects of primary care represented in the scale, "shared experience" was most difficult for parents to endorse in Rasch modeling. All 11 items contributed significantly to the total scale score with corrected item-total correlations >0.4. The PCPCM score was independent of socio demographics and was associated with parent's report that their child's clinician spends enough time with them. CONCLUSIONS: The PCPCM performs well in a pediatric continuity clinic setting, warranting consideration for its use as a parsimonious parent-reported measure of what patients and clinicians say matters most in pediatric primary care.

Using ICD-10 codes to identify elective epilepsy monitoring unit admissions from administrative billing data: A validation study.

Video-electroencephalogram (EEG) monitoring in the epilepsy monitoring unit (EMU) is essential for managing epilepsy and seizure mimics. Evaluation of care in the EMU would benefit from a validated code set capable of identifying EMU admissions from administrative databases comprised of large, diverse cohorts. We assessed the ability of code-based queries to parse EMU admissions from administrative billing records in a large academic medical center over a four-year period, 2016-2019. We applied prespecified queries for admissions coded as follows: 1) elective, 2) receiving video-EEG monitoring, and 3) including diagnoses typically required by major US healthcare payers for EMU admission. Sensitivity (Sn), specificity (Sp), and predictive value positive/negative (PVP, PVN) were determined. Two approaches were highly effective. Incorporating epilepsy, seizure, or seizure mimic codes as the admitting diagnosis (assigned at admission; Sn 96.3%, Sp 100.0%, PVP 98.3%, and PVN 100.0%) or the principal diagnosis (assigned after discharge; Sn 94.9%, Sp 100.0%, PVP 98.8%, and PVN 100.0%) identified elective adult EMU admissions with comparable reliability (p = 0.096). The addition of surgical procedure codes further separated EMU admissions for intracranial EEG monitoring. When applied to larger, more comprehensive datasets, these code-based queries should enhance our understanding of EMU utilization and access to care on a scalable basis.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).

Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units.

IMPORTANCE: The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). OBJECTIVE: To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. MAIN OUTCOMES AND MEASURES: Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. RESULTS: Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. CONCLUSIONS AND RELEVANCE: This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

Depression, Anxiety, and Emergency Department Use for Asthma.

BACKGROUND AND OBJECTIVES: Asthma is responsible for ∼1.7 million emergency department (ED) visits annually in the United States. Studies in adults have shown that anxiety and depression are associated with increased asthma-related ED use. Our objective was to assess this association in pediatric patients with asthma. METHODS: We identified patients aged 6 to 21 years with asthma in the Massachusetts All-Payer Claims Database for 2014 to 2015 using International Classification of Diseases, Ninth and 10th Revision codes. We examined the association between the presence of anxiety, depression, or comorbid anxiety and depression and the rate of asthma-related ED visits per 100 child-years using bivariate and multivariable analyses with negative binomial regression. RESULTS: Of 65 342 patients with asthma, 24.7% had a diagnosis of anxiety, depression, or both (11.2% anxiety only, 5.8% depression only, and 7.7% both). The overall rate of asthma-related ED use was 17.1 ED visits per 100 child-years (95% confidence interval [CI]: 16.7-17.5). Controlling for age, sex, insurance type, and other chronic illness, patients with anxiety had a rate of 18.9 (95% CI: 17.0-20.8) ED visits per 100 child-years, patients with depression had a rate of 21.7 (95% CI: 18.3-25.0), and patients with both depression and anxiety had a rate of 27.6 (95% CI: 24.8-30.3). These rates were higher than those of patients who had no diagnosis of anxiety or depression (15.5 visits per 100 child-years; 95% CI: 14.5-16.4; P < .001). CONCLUSIONS: Children with asthma and anxiety or depression alone, or comorbid anxiety and depression, have higher rates of asthma-related ED use compared with those without either diagnosis.

A Learning Loop Model of Collaborative Decision-Making in Chronic Illness.

Shared decision-making is a core attribute of quality health care that has proved challenging to implement and assess in pediatric practice. Current models of shared decision-making are limited, including their capacity to incorporate multiple stakeholders; to integrate downstream effects of subacute or minor decisions; and to account for the context(s) in which such decisions are being made and enacted. Based on a review of literature from organizational psychology, cognitive sciences, business, and medicine, we propose an iterative decision-making model of care planning and identify targets at several levels of influence warranting measurement in future studies. Our learning loop model posits the relationship between pediatric patients, their parents, and their clinicians as central to the collaborative decision-making process in the setting of chronic illness. The model incorporates the evolution of both context and developmental capacity over time. It suggests that "meta-learning" from the experience of and outcomes from iterative decision is a key factor that may influence relationships and thus continued engagement in collaboration by patients, their parents, and their clinicians. We consider the model in light of the needs of children with special health care needs, for whom understanding the ongoing iterative effects of decision making and clinician-parent-child dynamics are likely to be particularly important in influencing outcomes.

Variation of the prevalence of pediatric polypharmacy: A scoping review.

PURPOSE: To examine the range of prevalence of pediatric polypharmacy in literature through a scoping review, focusing on factors that contribute to its heterogeneity in order to improve the design and reporting of quality improvement, pharmacovigilance, and research studies. METHODS: We searched Ovid Medline, PubMed, EMBASE, CINAHL, Ovid PsycINFO, Cochrane CENTRAL, and Web of Science Core Collection databases for studies with concepts of children and polypharmacy, along with a hand search of the bibliographies of six reviews and 30 included studies. We extracted information regarding study design, disease conditions, and prevalence of polypharmacy. RESULTS: Two hundred eighty-four studies reported prevalence of polypharmacy. They were more likely to be conducted in North America (37.7%), published after 2010 (44.4%), cross-sectional (67.3%), in outpatient settings (59.5%). Prevalence ranged from 0.9% to 98.4%, median 39.7% (interquartile range [IQR] 22.0%-54.0%). Studies from Asia reported the highest median prevalence of 45.4% (IQR 27.3%-61.0%) while studies from North America reported the lowest median prevalence of 30.4% (IQR 14.7%-50.2%). Prevalence decreased over time: median 45.6% before 2001, 38.1% during 2001 to 2010, and 34% during 2011 to 2017. Studies involving children under 12 years had a higher median prevalence (46.9%) than adolescent studies (33.7%). Inpatient setting studies had a higher median prevalence (50.3%) than studies in outpatient settings (38.8%). Community level samples, higher number and duration of medications defining polypharmacy, and psychotropic medications were associated with lower prevalence. CONCLUSIONS: The prevalence of pediatric polypharmacy is high and variable. Studies reporting pediatric polypharmacy should account for context, design, polypharmacy definition, and medications evaluated.

Estimated Nonreimbursed Costs for Care Coordination for Children With Medical Complexity.

: media-1vid110.1542/5852348672001PEDS-VA_2017-3562Video Abstract BACKGROUND AND OBJECTIVES: Multidisciplinary care teams may improve health and control total cost for children with medical complexity (CMC). We aim to quantify the time required to perform nonreimbursed care coordination activities by a multidisciplinary care coordination program for CMC and to estimate the direct salary costs of that time. METHODS: From April 2013 to October 2015, program staff tracked time spent in practicably measured nonbilled care coordination efforts. Staff documented the discipline involved, the method used, and the target of the activity. Cost was estimated by multiplying the time spent by the typical salary of the type of personnel performing the activity. RESULTS: Staff logged 53 148 unique nonbilled care coordination activities for 208 CMC. Dietitians accounted for 26% of total time, physicians and nurse practitioners 24%, registered nurses 29%, and social workers 21% (1.8, 2.3, 1.2, and 1.4 hours per CMC per month per full-time provider, respectively). Median time spent in nonreimbursed care coordination was 2.3 hours per child per month (interquartile range 0.8-6.8). Enrollees required substantially greater time in their first program month than thereafter (median 6.7 vs 2.1 hours per CMC per month). Based on 2015 national salary data, the adjusted median estimated cost of documented activities ranged from $145 to $210 per CMC per month. CONCLUSIONS: In this multidisciplinary model, care coordination for CMC required substantial staff time, even without accounting for all activities, particularly in the first month of program enrollment. Continued advocacy is warranted for the reimbursement of care coordination activities for CMC.