Tracking Staff Mood and Concerns in a Pediatric Emergency Department During the COVID-19 Pandemic.

INTRODUCTION: Few studies have monitored health care worker mood and job satisfaction changes longitudinally throughout an epidemic. The objective of this study was to track staff mood, job satisfaction, questions, and suggestions in a pediatric emergency department over 1 year during the coronavirus disease 2019 pandemic. We hypothesized that staff would experience heightened negative emotions earlier in the pandemic due to uncertainty around hospital protocols and the coronavirus disease 2019 disease process. METHODS: A voluntary, cross sectional descriptive study using an anonymous electronic survey assessed job satisfaction and mood over 4 domains (sad-happy, angry-peaceful, exhausted-energized, fearful-confident) in pediatric emergency department staff members. Responses were reported with Likert scales and free-text fields. RESULTS: Of 272 survey responses, most were from nurses and clinical technicians (N = 173, 63.6%), followed by physicians and physician assistants (N = 55, 20.2%) and nonmedical staff (N = 44, 16.2%). Department-wide values for the fearful-confident and angry-peaceful domains increased over time (P = .001 and P = .01, respectively), indicating an overall more confident and peaceful mood in department staff. Job satisfaction did not change over time or by staff role. Nurses and clinical technicians reported the most exhaustion (P = .002), and physicians and physician assistants reported the most fear (P = .03). We received a total of 71 comments, which we grouped into 4 themes: protocols and procedures, personnel, infection risk, and miscellaneous. Comments submitted early in the pandemic centered around intradepartmental protocols and procedures, with a peak in staffing comments 5 months into the pandemic. DISCUSSION: An electronic survey monitoring mood, job satisfaction, and concerns in a pediatric emergency department identified mood changes in staff over the course of the coronavirus disease 2019 pandemic.

Distinct Cytokine and Chemokine Dysregulation in Hospitalized Children With Acute Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome With Similar Levels of Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 Shedding.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe clinical phenotype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that remains poorly understood. METHODS: Hospitalized children <18 years of age with suspected coronavirus disease 2019 (COVID-19) (N = 53) were recruited into a prospective cohort study; 32 had confirmed COVID-19, with 16 meeting the US Centers for Disease Control criteria for MIS-C. Differences in nasopharyngeal viral ribonucleic acid (RNA) levels, SARS-CoV-2 seropositivity, and cytokine/chemokine profiles were examined, including after adjustments for age and sex. RESULTS: The median ages for those with and without MIS-C were 8.7 years (interquartile range [IQR], 5.5-13.9) and 2.2 years (IQR, 1.1-10.5), respectively (P = .18), and nasopharyngeal levels of SARS-CoV-2 RNA did not differ significantly between the 2 groups (median 63 848.25 copies/mL versus 307.1 copies/mL, P = .66); 75% of those with MIS-C were antibody positive compared with 44% without (P = .026). Levels of 14 of 37 cytokines/chemokines (interleukin [IL]-1RA, IL-2RA, IL-6, IL-8, tumor necrosis factor-α, IL-10, IL-15, IL-18, monocyte chemoattractant protein [MCP]-1, IP-10, macrophage-inflammatory protein [MIP]-1α, MCP-2, MIP-1ß, eotaxin) were significantly higher in children with MIS-C compared to those without, irrespective of age or sex (false discovery rate <0.05; P < .05). CONCLUSIONS: The distinct pattern of heightened cytokine/chemokine dysregulation observed with MIS-C, compared with acute COVID-19, occurs across the pediatric age spectrum and with similar levels of nasopharyngeal SARS-CoV-2 RNA.

Brief Report: The Experiences of Families of Children with an Autism Spectrum Disorder When Seeking Patient-and Family-Centered Care.

Patient-and family-centered care (PFCC) is a partnership among healthcare professionals, patients, and families that is grounded in mutual respect and is an approach that impacts delivery of care, decision-making, and information sharing. PFCC should be implemented for all, including individuals with Autism Spectrum Disorders (ASD), who experience adverse medical encounters despite increased prevalence and healthcare utilization. Insights into the experiences of families during medical experiences can inform clinical practice by increasing healthcare professionals' understanding of the population. Using a mixed-methods approach, the perspectives of 40 families were analyzed. The themes include barriers and opportunities to improve upon the delivery of PFCC, which help to advance healthcare interactions and inform solution-based initiatives to facilitate medical visits that may benefit all patients.

Cross-reactivity of SARS-CoV-2- and influenza A-specific T cells in individuals exposed to SARS-CoV-2.

Cross-reactive immunity between SARS-CoV-2 and other related coronaviruses has been well-documented, and it may play a role in preventing severe COVID-19. Epidemiological studies early in the pandemic showed a geographical association between high influenza vaccination rates and lower incidence of SARS-CoV-2 infection. We, therefore, analyzed whether exposure to influenza A virus (IAV) antigens could influence the T cell repertoire in response to SARS-CoV-2, indicating a heterologous immune response between these 2 unrelated viruses. Using artificial antigen-presenting cells (aAPCs) combined with real-time reverse-transcription PCR (RT-qPCR), we developed a sensitive assay to quickly screen for antigen-specific T cell responses and detected a significant correlation between responses to SARS-CoV-2 epitopes and IAV dominant epitope (M158-66). Further analysis showed that some COVID-19 convalescent donors exhibited both T cell receptor (TCR) specificity and functional cytokine responses to multiple SARS-CoV-2 epitopes and M158-66. Utilizing an aAPC-based stimulation/expansion assay, we detected cross-reactive T cells with specificity to SARS-CoV-2 and IAV. In addition, TCR sequencing of the cross-reactive and IAV-specific T cells revealed similarities between the TCR repertoires of the two populations. These results indicate that heterologous immunity shaped by our exposure to other unrelated endemic viruses may affect our immune response to novel viruses such as SARS-CoV-2.

SARS-CoV-2 as a superantigen in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but deadly new disease in children that rapidly progresses to hyperinflammation and shock, and can lead to multiple organ failure if unrecognized. It has been found to be temporally associated with the COVID-19 pandemic and is often associated with SARS-CoV-2 exposure in children. In this issue of the JCI, Porritt, Paschold, et al. identify restricted T cell receptor (TCR) ß-chain variable domain (Vß) usage in patients with severe MIS-C, indicating a potential role for SARS-CoV-2 as a superantigen. These findings suggest that a blood test that determines the presence of specific TCRß variable gene (TRBV) segments may identify patients at risk for severe MIS-C.

A Scoping Review of Targeted Interventions and Training to Facilitate Medical Encounters for School-Aged Patients with an Autism Spectrum Disorder.

Individuals with an autism spectrum disorder (ASD) have a greater number of healthcare provider interactions than individuals without ASD. The obstacles to patient-centered care for this population, which include inflexibility of hospital environments, limited resources, and inadequate training, has been documented. However, there is little knowledge on efforts to address such concerns. A scoping review was conducted and the systematic search of the literature resulted in 23 relevant studies. The predominant themes include the use of data collection instruments, application of evidence-based practices and resources, and training of providers. The results of this review have implications for practitioners and future research to adapt and improve upon the provision of medical care for individuals with ASD across the lifespan.

Assessing Ease of Delivering Emergency Care for Patients with Autism Spectrum Disorders.

OBJECTIVE: The aim of this study was to develop a method for objectively assessing the delivery of care to children with autism spectrum disorder (ASD) in the emergency department (ED). METHODS: A case-control study of patients ages 2 to 18 years admitted to the hospital from January 2016 to January 2018. Cases were defined as patients with an International Classification of Diseases, Tenth Revision diagnosis of ASD or other pervasive developmental disorder (F84) in their medical record and were matched 1:1 with neurotypical controls. The primary outcome was ability to complete several core tasks clinically necessary within an ED visit and summarized into a Task Completion Index (TCI). RESULTS: Overall, children with ASD had higher median TCIs of 0.25 (interquartile range [IQR] 0-0.45) versus 0 (IQR 0-0.25) when compared with children without ASD (p < 0.01). Children with ASD were 5 times more likely to have difficulty with triage vitals, 3 times more likely to require additional staff for peripheral intravenous placement, and 4 times more likely to experience delays or disruptions to their plan of care. The TCI was also associated with 8-fold increased odds of receiving pharmacologic or physical restraint. CONCLUSIONS: The TCI reflects difficulty accomplishing core tasks necessary to complete an ED visit. Children with ASD have higher TCIs than neurotypical controls, which puts them at higher risk for care disruptions. Evaluation of initiatives to improve quality of care for children with ASD should focus not only on metrics of overall experience and satisfaction but also how these initiatives affect the ability to effectively administer care.

Use of white cell count, age, and presence of other injuries in stratifying risk of intracranial injury in pediatric trauma.

The Pediatric Emergency Care Applied Research Network (PECARN) Head Injury/Trauma Algorithm is a well-validated decision rule used to identify patients at low risk of clinically important traumatic brain injuries who may not need head CT. In adult patients with mild head trauma, elevated serum glucose and white cell count (WCC) have been associated with abnormal head CT findings. Currently, glucose or WCC is not considered in pediatric patients. The objective of this study was to determine if elevations in glucose or WCC could be used as additional tools to risk-stratify pediatric trauma patients for intracranial injury (ICI). Data were abstracted from the Maryland Trauma Registry and from electronic medical records for patients at the Johns Hopkins Children's Center from 2017 to 2020. We evaluated 145 encounters that met the inclusion criteria. There were 33 cases of ICI on CT. In addition to higher median glucose and WCC, we found that patients with ICI had a younger median age and were less likely to have other clinically significant injuries than patients without ICI. Following multiple logistic regression analysis, WCC (OR 1.113, 95% CI 1.02 to 1.21), younger age (OR 0.89, 95% CI 0.8 to 0.98), and absence of other injuries (OR 0.41, 95% CI 0.23 to 0.73) were found to be associated with risk of ICI. The area under the curve for our model was 0.79. When used with the PECARN algorithm, our model could help determine which patients may avoid head CT or undergo a shorter observation period.

A Resident-Led QI Initiative to Improve Pediatric Emergency Department Boarding Times.

BACKGROUND: Pediatric emergency department (PED) overcrowding and prolonged boarding times (admission order to PED departure) decrease quality of care. Timely transfer of patients from the PED to inpatient units is a key driver that relieves overcrowding. In 2015, PED boarding time at our hospital was 10% longer than the national benchmark. We described a resident-led quality-improvement initiative to decrease PED mean boarding times by 10% (from 173 to 156 minutes) within 6 months among general pediatric admissions. METHODS: We applied Plan-Do-Study-Act (PDSA) methodology. PDSA 1 (October 2016) interventions were bundled to include streamlined mobile communications, biweekly educational presentations, and reminder signs. PDSA 2 (August 2017) provided alternative workflows for senior residents. Outcomes were mean PED boarding times for general pediatrics admissions. The proportion of PICU transfers within 12 hours of admission served as a balancing measure. Statistical process control charts were used to analyze boarding times and PICU transfer rates. RESULTS: Leading up to PDSA 1, monthly mean boarding times decreased from 173 to 145 minutes and were sustained throughout the study period and up to 1 year after study completion. The X-bar chart demonstrated a shift with 57 consecutive months of mean boarding times below the preintervention mean. There were no changes in PICU transfer rates within 12 hours of admission. CONCULSIONS: Resident-led quality improvement efforts, including education and streamlined workflow, significantly improved PED boarding time without causing harm to patients.

Influenza A virus (H3N8) in dogs with respiratory disease, Florida.

In 2004, canine influenza virus subtype H3N8 emerged in greyhounds in the United States. Subsequent serologic evidence indicated virus circulation in dog breeds other than greyhounds, but the virus had not been isolated from affected animals. In 2005, we conducted virologic investigation of 7 nongreyhound dogs that died from respiratory disease in Florida and isolated influenza subtype H3N8 virus. Antigenic and genetic analysis of A/canine/Jacksonville/2005 (H3N8) and A/canine/Miami/2005 (H3N8) found similarity to earlier isolates from greyhounds, which indicates that canine influenza viruses are not restricted to greyhounds. The hemagglutinin contained 5 conserved amino acid differences that distinguish canine from equine lineages. The antigenic homogeneity of the canine viruses suggests that measurable antigenic drift has not yet occurred. Continued surveillance and antigenic analyses should monitor possible emergence of antigenic variants of canine influenza virus.

Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells.

Galectin-3 is a 31-kDa lectin that modulates T-cell responses through several mechanisms, including apoptosis, T-cell receptor (TCR) cross-linking, and TCR downregulation. We found that patients with pancreatic ductal adenocarcinoma (PDA) who responded to a granulocyte-macrophage colony-stimulating factor-secreting allogeneic PDA vaccine developed neutralizing antibodies to galectin-3 after immunization. We show that galectin-3 binds activated antigen-committed CD8(+) T cells only in the tumor microenvironment. Galectin-3-deficient mice exhibit improved CD8(+) T-cell effector function and increased expression of several inflammatory genes. Galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3-mediated suppression of CD8(+) T cells in vitro. Lastly, galectin-3-deficient mice have elevated levels of circulating plasmacytoid dendritic cells, which are superior to conventional dendritic cells in activating CD8(+) T cells. Thus, inhibiting galectin-3 in conjunction with CD8(+) T-cell-directed immunotherapies should enhance the tumor-specific immune response.

Trafficking of high avidity HER-2/neu-specific T cells into HER-2/neu-expressing tumors after depletion of effector/memory-like regulatory T cells.

BACKGROUND: Cancer vaccines are designed to activate and enhance cancer-antigen-targeted T cells that are suppressed through multiple mechanisms of immune tolerance in cancer-bearing hosts. T regulatory cell (Treg) suppression of tumor-specific T cells is one barrier to effective immunization. A second mechanism is the deletion of high avidity tumor-specific T cells, which leaves a less effective low avidity tumor specific T cell repertoire available for activation by vaccines. Treg depleting agents including low dose cyclophosphamide (Cy) and antibodies that deplete CD25-expressing Tregs have been used with limited success to enhance the potency of tumor-specific vaccines. In addition, few studies have evaluated mechanisms that activate low avidity cancer antigen-specific T cells. Therefore, we developed high and low avidity HER-2/neu-specific TCR transgenic mouse colonies specific for the same HER-2/neu epitope to define the tolerance mechanisms that specifically affect high versus low avidity tumor-specific T cells. METHODOLOGY/PRINCIPAL FINDINGS: High and low avidity CD8(+) T cell receptor (TCR) transgenic mice specific for the breast cancer antigen HER-2/neu (neu) were developed to provide a purified source of naïve, tumor-specific T cells that can be used to study tolerance mechanisms. Adoptive transfer studies into tolerant FVB/N-derived HER-2/neu transgenic (neu-N) mice demonstrated that high avidity, but not low avidity, neu-specific T cells are inhibited by Tregs as the dominant tolerizing mechanism. High avidity T cells persisted, produced IFNγ, trafficked into tumors, and lysed tumors after adoptive transfer into mice treated with a neu-specific vaccine and low dose Cy to deplete Tregs. Analysis of Treg subsets revealed a Cy-sensitive CD4(+)Foxp3(+)CD25(low) tumor-seeking migratory phenotype, characteristic of effector/memory Tregs, and capable of high avidity T cell suppression. CONCLUSION/SIGNIFICANCE: Depletion of CD25(low) Tregs allows activation of tumor-clearing high avidity T cells. Thus, the development of agents that specifically deplete Treg subsets should translate into more effective immunotherapies while avoiding autoimmunity.