Newborn screening for Duchenne muscular dystrophy: A two-year pilot study.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre-symptomatic diagnosis. METHODS: At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD. The first-tier screen measured creatine kinase-MM (CK-MM) in dried blood spot specimens submitted for routine NBS. Newborns with elevated CK-MM were referred for genetic counseling and genetic testing. The latter included deletion/duplication analysis and next-generation sequencing (NGS) of the DMD gene followed by NGS for a panel of neuromuscular conditions if no pathogenic variants were detected in the DMD gene. RESULTS: In the two-year pilot study, 36,781 newborns were screened with CK-MM. Forty-two newborns (25 male and 17 female) were screen positive and referred for genetic testing. Deletions or duplications in the DMD gene were detected in four male infants consistent with DMD or Becker muscular dystrophy. One female DMD carrier was identified. INTERPRETATION: This study demonstrated that the state NBS program infrastructure and screening technologies we used are feasible to perform NBS for DMD. With an increasing number of treatment options, the clinical utility of early identification for affected newborns and their families lends support for NBS for this severe disease.

Six Month Follow-up of Patients With Multi-System Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: Myocardial dysfunction and coronary abnormalities are prominent features of multisystem inflammatory syndrome in children (MIS-C). In this study we aim to evaluate the early and midterm outcomes of MIS-C. METHODS: This is a longitudinal 6-month cohort study of all children admitted and treated for MIS-C from April 17 to June 20, 2020. Patients were followed ∼2 weeks, 8 weeks, and 6 months postadmission, with those with coronary aneurysms evaluated more frequently. RESULTS: Acutely, 31 (62%) patients required intensive care with vasoactive support, 26 (52%) had left ventricular (LV) systolic dysfunction, 16 (32%) had LV diastolic dysfunction, 8 (16%) had coronary aneurysms (z score ≥2.5), and 4 (8%) had coronary dilation (z score <2.5). A total of 48 patients (96%) received immunomodulatory treatment. At 2 weeks, there was persistent mild LV systolic dysfunction in 1 patient, coronary aneurysms in 2, and dilated coronary artery in 1. By 8 weeks through 6 months, all patients returned to functional baseline with normal LV systolic function and resolution of coronary abnormalities. Cardiac MRI performed during recovery in select patients revealed no myocardial edema or fibrosis. Some patients demonstrated persistent diastolic dysfunction at 2 weeks (5, 11%), 8 weeks (4, 9%), and 6 months (1, 4%). CONCLUSIONS: Children with MIS-C treated with immunomodulators have favorable early outcomes with no mortality, normalization of LV systolic function, recovery of coronary abnormalities, and no inflammation or scarring on cardiac MRI. Persistence of diastolic dysfunction is of uncertain significance and indicates need for larger studies to improve understanding of MIS-C. These findings may help guide clinical management, outpatient monitoring, and considerations for sports clearance.

Features of Intestinal Disease Associated With COVID-Related Multisystem Inflammatory Syndrome in Children.

ABSTRACT: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified syndrome that appears to be temporally associated with novel coronavirus 2019 infection. MIS-C presents with fever and evidence of systemic inflammation, which can manifest as cardiovascular, pulmonary, neurologic, and gastrointestinal (GI) system dysfunction. Presenting GI symptoms are seen in the majority, including abdominal pain, diarrhea, and vomiting. Any segment of the GI tract may be affected; however, inflammation in the ileum and colon predominates. Progressive bowel wall thickening can lead to luminal narrowing and obstruction. Most will have resolution of intestinal inflammation with medical therapies; however, in rare instances, surgical resection may be required.

Cost of survivorship care and adherence to screening-aligning the priorities of health care systems and survivors.

Childhood cancer survivors (CCS) experience significant morbidity due to treatment- related late effects and benefit from late-effects surveillance. Adherence to screening recommendations is suboptimal. Survivorship care programs often struggle with resource limitations and may benefit from understanding institution-level financial outcomes associated with patient adherence to justify programmatic development and growth. The purpose of this study is to examine how CCS adherence to screening recommendations relates to the cost of care, insurance status, and institution-level financial outcomes. A retrospective chart review of 286 patients, followed in a structured survivorship program, assessed adherence to the Children's Oncology Group follow-up guidelines by comparing recommended versus performed screening procedures for each patient. Procedure cost estimates were based on insurance status. Institutional profit margins and profit opportunity loss were calculated. Bivariate statistics tested adherent versus nonadherent subgroup differences on cost variables. A generalized linear model predicted the likelihood of adherence based on cost of recommended procedures, controlling for age, gender, race, and insurance. Adherence to recommended surveillance procedures was 50.2%. Nonadherence was associated with higher costs of recommended screening procedures compared to the adherent group estimates ($2,469.84 vs. $1,211.44). Failure to perform the recommended tests resulted in no difference in reimbursement to the health system between groups ($1,249.63 vs. $1,211.08). For the nonadherent group, this represented $1,055.13 in "lost profit opportunity" per visit for patients, which totaled $311,850 in lost profit opportunity due to nonadherence in this subgroup. In the final model, nonadherence was related to higher cost of recommended procedures (p < .0001), older age at visit (p = .04), Black race (p = .02), and government-sponsored insurance (p = .03). Understanding institutional financial outcomes related to patient adherence may help inform survivorship care programs and resource allocation. Potential financial burden to patients associated with complex care recommendations is also warranted.

Characteristics and risk factors associated with critical illness in pediatric COVID-19.

BACKGROUND: While much has been reported regarding the clinical course of COVID-19 in children, little is known regarding factors associated with organ dysfunction in pediatric COVID-19. We describe critical illness in pediatric patients with active COVID-19 and identify factors associated with PICU admission and organ dysfunction. This is a retrospective chart review of 77 pediatric patients age 1 day to 21 years admitted to two New York City pediatric hospitals within the Northwell Health system between February 1 and April 24, 2020 with PCR + SARS-CoV-2. Descriptive statistics were used to describe the hospital course and laboratory results and bivariate comparisons were performed on variables to determine differences. RESULTS: Forty-seven patients (61%) were admitted to the general pediatric floor and thirty (39%) to the PICU. The majority (97%, n = 75) survived to discharge, 1.3% (n = 1) remain admitted, and 1.3% (n = 1) died. Common indications for PICU admission included hypoxia (50%), hemodynamic instability (20%), diabetic ketoacidosis (6.7%), mediastinal mass (6.7%), apnea (6.7%), acute chest syndrome in sickle cell disease (6.7%), and cardiac dysfunction (6.7%). Of PICU patients, 46.7% experienced any significant organ dysfunction (pSOFA > = 2) during admission. Patients aged 12 years or greater were more likely to be admitted to a PICU compared to younger patients (p = 0.015). Presence of an underlying comorbidity was not associated with need for PICU admission (p = 0.227) or organ dysfunction (p = 0.87). Initial white blood cell count (WBC), platelet count, and ferritin were not associated with need for PICU admission. Initial C-reactive protein was associated with both need for PICU admission (p = 0.005) and presence of organ dysfunction (p = 0.001). Initial WBC and presenting thrombocytopenia were associated with organ dysfunction (p = 0.034 and p = 0.003, respectively). CONCLUSIONS: Age over 12 years and initial CRP were associated with need for PICU admission in COVID-19. Organ dysfunction was associated with elevated admission CRP, elevated WBC, and thrombocytopenia. These factors may be useful in determining risk for critical illness and organ dysfunction in pediatric COVID-19.

Early Experience of COVID-19 in a US Children's Hospital.

OBJECTIVES: We aim to describe the demographics, clinical presentation, hospital course, and severity of pediatric inpatients with coronavirus disease 2019 (COVID-19), with an emphasis on healthy, immunocompromised, and chronically ill children. METHODS: We conducted a single-center retrospective cohort study of hospitalized children aged younger than 22 years with COVID-19 infection at Steven and Alexandra Cohen Children's Medical Center at Northwell Health. Cases were identified from patients with fever and/or respiratory symptoms who underwent a nucleic acid amplification-based test for severe acute respiratory syndrome coronavirus 2. RESULTS: Sixty-five patients were identified. The median age was 10.3 years (interquartile range, 1.4 months to 16.3 years), with 48% of patients older than 12 years and 29% of patients younger than 60 days of age. Fever was present in 86% of patients, lower respiratory symptoms or signs in 60%, and gastrointestinal symptoms in 62%. Thirty-five percent of patients required ICU care. The white blood cell count was elevated in severe disease (P = .0027), as was the C-reactive protein level (P = .0192), compared with mild and moderate disease. Respiratory support was required in 34% of patients. Severity was lowest in infants younger than 60 days of age and highest in chronically ill children; 79% of immunocompromised children had mild disease. One death was reported. CONCLUSIONS: Among children who are hospitalized for COVID-19, most are younger than 60 days or older than 12 years of age. Children may have severe infection requiring intensive care support. The clinical course of immunocompromised patients was not more severe than that of other children. Elevated white blood cell count and C-reactive protein level are associated with greater illness severity.

Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR-positive SARS-CoV-2 infection, including drug-induced changes in the corrected QT interval.

BACKGROUND: There is limited data regarding the electrophysiological abnormalities and arrhythmias in children with COVID-19, including those associated with treatment using potentially proarrhythmic hydroxychloroquine (HCQ) and azithromycin (AZN). OBJECTIVES: To describe the electrophysiologic findings and arrhythmias associated with pediatric COVID-19 and its treatment. METHODS: A single-center retrospective chart review was undertaken and included all patients with (1) symptoms of COVID-19 and (2) PCR-positive nasopharyngeal swabs for SARS-CoV-2 who were placed on continuous telemetry for the duration of their hospitalization during March through May, 2020. RESULTS: Thirty-six patients were included in the study. Significant arrhythmias were found in 6 (nonsustained ventricular tachycardia in 5 and sustained atrial tachycardia in 1). All were self-resolving and half prompted prophylactic antiarrhythmic therapy. Patients with significant arrhythmias were likely to have noncardiac comorbidities (4/6), but these were not more common than in patients without arrhythmias (20/30, P = 1). The use of HCQ was associated with statistically significant QTc prolongation (413 ± 19 ms vs 425 ± 16 ms, P =.005). QTc was not statistically different in patients with and without arrhythmias (425 ± 15 ms vs 425 ± 15 ms, P = 1). CONCLUSIONS: In pediatric patients with PCR-positive active COVID-19 infection, significant arrhythmias are infrequent, but are more common than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. COVID-19 treatment using HCQ is associated with QTc prolongation but was not associated with arrhythmias in pediatric patients.

Characteristics, Cardiac Involvement, and Outcomes of Multisystem Inflammatory Syndrome of Childhood Associated with severe acute respiratory syndrome coronavirus 2 Infection.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection. Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

Novel Approach to Emergency Departments' Pediatric Readiness Across a Health System.

STUDY OBJECTIVE: A gap analysis of emergency departments' (EDs') pediatric readiness across a health system was performed after the appointment of a service line health system pediatric emergency medicine (PEM) quality director. METHODS: A 55-question survey was completed by each eligible ED to generate a weighted pediatric readiness score (WPRS). The survey included questions regarding volume, ED configuration, presence of a pediatric emergency care coordinator (PECC), quality initiatives, policies and procedures, and equipment. Surveys were completed from June 1 to November 12, 2016.Analysis of variance was used to compare the 4 groups of EDs based upon their annual pediatric volume as a continuous measure (low, <1800 visits; medium, 1800-4999 visits; medium-high, 5000-9999 visits; high, >10,000 visits). The Fisher exact test was used to compare the 4 groups for the remaining categorical variables represented as frequencies and percentages. A result was considered statistically significant at the P < 0.05 level of significance. RESULTS: There were a total of 16 hospitals (after the exclusion of the children's hospital, the hub for pediatric care in the health system, and 1 adult-only hospital) with the following pediatric capability: 7 basic (no inpatient pediatrics), 7 general (inpatient pediatrics, with/without a neonatal intensive care unit), and 2 comprehensive (inpatient pediatrics, pediatric intensive care unit, and a neonatal intensive care unit). In 12 EDs, adults and children are treated in the same space. These EDs see a total of 800,000 annual visits including 120,000 pediatric visits. Two low pediatric volume EDs had a median WPRS of 69, range of 62 to 76 (national median, 61.4); 6 medium pediatric volume EDs had a median WPRS of 51, range of 42 to 81 (national median, 69.3); 4 medium-high pediatric volume EDs had a median WPRS of 69.3, range of 45 to 98 (national medium, 74.8); 4 high pediatric volume EDs had a WPRS score of 84.5, range of 58 to 100 (national medium, 89.8). There were 4 sites with PECCs: 1 medium-high volume and 3 high volume, with a median WPRS of 98.5, range of 81 to 100 (national medium, 89.8). Two low-volume EDs have Neonatal Resuscitation Program training for nurses (P < 0.0083). One medium-high volume ED requires specific pediatric competency evaluations for advanced level practitioners staffing the ED. Pediatric-specific quality programs are present in the 2 low volume EDs, 3 of the 6 EDs in the medium group, 3 of 4 EDs in the medium-high group, and all 4 high volume hospitals. After the implementation of the health system PEM quality director, all EDs have a doctor and nurse PECC with a median WPRS of 81. In additiona, a committee was formed with the following key stakeholders: PECCs, pediatric nursing educators, pediatric quality, pharmacy, obstetrics, behavioral health, and neonatology. The committee is part of the health system quality program within both pediatrics and emergency medicine and is spearheading the standardization of code carts and medications, dissemination of pediatric clinical guidelines, and the development of a pediatric quality program across the health system. CONCLUSIONS: Pediatric emergency care coordinators play an important role in ED readiness to care for pediatric patients. In a large health system, a service line PEM quality director with the support of emergency medicine and pediatrics, a committee with solid frontline ED base, and a diverse array of stakeholders can foster the engagement of all EDs and improve compliance with published guidelines.

Characterization of the Development of Acute-on-Chronic Exertional Compartment Syndrome A Case Report of Symmetric Compartment Syndromes and Review of the Literature.

Acute-on-chronic exertional compartment syndrome is a rare and severe progression of the likely common and more benign chronic exertional compartment syndrome. This is a report of one 17-year-old male on a pediatric inpatient service with bilateral anterior leg pain of unknown origin. Because of the nonspecific nature of pain, a high level of suspicion is required for timely diagnosis to avoid compartment ischemia and irreversible soft tissue and nerve damage. While high-energy orthopaedic trauma, orthopaedic surgery, or closed reduction and casting are common preceding events for compartment syndrome, this patient presented with acute-on-chronic exertional compartment syndrome. A dearth of literature of this condition hampered its morbiditysparing diagnosis. While there is a spectrum of clinical findings for the acute decompensation of chronic exertional compartment syndrome, like any compartment syndrome, pain disproportionate to physical exam is the most sensitive sign. Understanding the exertional compartment syndrome spectrum is tantamount to avoid the devastating complications of a missed diagnosis of acute compartment syndrome.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Looking for trouble: Adherence to late-effects surveillance among childhood cancer survivors.

BACKGROUND: Childhood cancer survivors (CCSs) are at high risk of morbidity and mortality from long-term complications of their cancer treatment. The Children's Oncology Group developed screening guidelines to enable the early identification of and intervention for late effects of cancer treatment. There is a paucity of data on the adherence of CCSs to screening recommendations. PROCEDURE: A retrospective analysis of medical records to evaluate the rate of adherence of CCSs to the personalized, risk-based recommendations provided to them in the context of a structured long-term follow-up program over a 3-year period. RESULTS: Two hundred eighty-six CCSs visited the survivorship clinic 542 times during the 3-year study period. The overall rate of adherence to recommended screening was 74.2%. Using a univariate model and greater age at diagnosis and at screening recommendation were associated with decreased screening adherence. Gender, cancer diagnosis, radiation therapy, anthracycline exposure, and hematopoietic stem cell transplant were not significantly associated with adherence. In a multivariate model, age over 18 years at the time of the visit was significantly associated with decreased adherence (P < 0.0329) (odds ratio: 1.53, 95% confidence interval: 1.04-2.25). CONCLUSIONS: Adherence to recommended screening tests is suboptimal among CCSs, with lower rates of adherence in CCSs older than 18 years of age compared with those younger than 18 years of age. Given the morbidity and mortality from the late effects of therapy among young adult CCSs, it is critically important to identify and remove barriers to late-effects screening among CCSs.