Patient Portal Enrollment for Discharged Pediatric Emergency Department Patients: A Multidisciplinary Quality Improvement Project.

Introduction: Patient portal enrollment following pediatric emergency department (ED) visits allows access to critical results, physician documentation, and telehealth follow-up options. Despite these advantages, there are many challenges to portal invitation and enrollment. Our primary objective was to improve patient portal enrollment rates for discharged pediatric ED patients. Methods: A multidisciplinary team of staff from two ED sites developed successful portal enrollment interventions through sequential Plan-Do-Study-Act cycles from October 2020 to October 2021. Interventions included a new invitation process, changes to patient paperwork on ED arrival, staff portal education, and changes to discharge paperwork and the portal website. The team utilized statistical process control charts to track the percentage of eligible discharged patients who received a portal invitation (process measure) and enrolled in the patient portal. Results: Before the study's initiation, less than 1% of eligible patients received patient portal invites or enrolled in the patient portal. Statistical process control charts revealed significant changes in enrollment and baseline shift at both a large academic ED campus and a satellite ED site by May 2021. Improvements in invitation rates were also observed at both campuses. Changes were sustained for over 6 months at both locations. Conclusions: High-reliability interventions and a multidisciplinary approach allowed for significant and sustained improvement in patient portal invitation and enrollment rates in eligible pediatric ED patients. Future study will examine enrollment patterns across patient demographics and further high-reliability interventions.

Impact of Using a Precompleted Consent Form for Procedural Sedation in the Pediatric Emergency Department.

OBJECTIVES: This study aimed to compare elements discussed during the consent process for procedural sedation in the pediatric emergency department to documentation and parental recall before and after implementation of a standardized consent form. METHODS: This is a mixed-methods study combining retrospective electronic record review and cross-sectional surveys of providers and parents after consent for procedural sedation. Surveys were obtained before and after implementation of a precompleted consent form. Providers' survey responses were compared with consent documentation. Recall of consent elements discussed by linked parent-provider dyads were compared. RESULTS: Six hundred fifty-five encounters were reviewed. Pediatric emergency medicine fellows and pediatric emergency department-based pediatricians were more likely to document any benefit (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.0-2.4) or alternative (OR, 2.7; 95% CI, 1.8-3.9) compared with PEM attendings. Providers were more likely to report discussion of failure to complete the procedure (OR, 7.3; 95% CI, 2.3-23.3) and parents were more likely to recall discussion of this risk (OR, 5.3; 95% CI, 1.0-27.8) in the postintervention group. Based on provider recall, using the precompleted consent form was associated with providers discussing at least 2 of the 3 benefits (84.0% vs 97.2%, P < 0.01), 5 of the 5 risks (31% vs 67.7%, P < 0.01), and improved parental recall of risks (5.7% vs 22.9%, P = 0.03). More providers reported taking less than 1 minute to complete the form in the postimplementation group (12.0% vs 43.7%, P < 0.01). CONCLUSIONS: Implementing a precompleted consent form for procedural sedation was associated with providers reporting decreased time spent completing the consent form and better alignment of key consent elements between reported provider discussion and parental recall.

Improving Adherence to Evidence-based Practice for Uncomplicated UTI in a Pediatric Emergency Department.

Introduction: Uncomplicated urinary tract infections (uUTIs) are among the more common pediatric bacterial infections. Despite their prevalence, significant variability exists in the treatment duration and antibiotic selection for uUTI. Our first aim was to improve adherence to a three-day course of antibiotic treatment for uUTI in children over 24 months old. Our second aim was to increase the selection of cephalexin in this population. Methods: We conducted a single-center quality improvement study from March 2021 to March 2022. One thousand four hundred thirty-five patients were included across our baseline and intervention periods. We created an order set with embedded discharge prescriptions and followed this with education and provider feedback. The outcome measures for this study were percent of children receiving 3 days of antibiotic treatment and percent of children prescribed cephalexin. In addition, we tracked order set use as a process measure, and 7-day emergency department revisit as a balancing measure. Results: Rates of 3-day prescriptions for uUTI demonstrated special cause variation with an increase from 3% to 44%. Prescription rates of cephalexin for uUTI demonstrated special cause variation with an increase from 49% to 74%. The process measure of order set use improved from 0% to 49% after implementation. No change occurred in 7-day emergency department revisits. Conclusion: We demonstrated improved use of shorter course therapy for uUTI with a first-generation cephalosporin throughout this project without adverse events. We leveraged an order set with embedded discharge prescriptions to achieve our goals.

Identifying pediatric patients with multisystem inflammatory syndrome in children presenting to a pediatric emergency department.

OBJECTIVE: To compare clinical and laboratory features of children with Multisystem Inflammatory Syndrome in Children (MIS-C) to those evaluated for MIS-C in the Emergency Department (ED). METHODS: We conducted a retrospective review of the medical record of encounters with testing for inflammatory markers in an urban, tertiary care Pediatric ED from March 1, 2020 to July 31, 2020. We abstracted demographic information, laboratory values, selected medications and diagnoses. We reviewed the record for clinical presentation for the subset of patients admitted to the hospital for suspected MIS-C. We then used receiver operating curves and logistic regression to evaluate the utility of candidate laboratory values to predict MIS-C status. RESULTS: We identified 32 patients with confirmed MIS-C and 15 admitted and evaluated for MIS-C but without confirmation of SARS CoV-2 infection. We compared these patients to 267 encounters with screening laboratories for MIS-C. Confirmed MIS-C patients had an older median age, higher median fever on presentation and were predominantly of Hispanic and non-Hispanic Black race/ethnicity. All children with MIS-C had a C-reactive protein (CRP) >4.5 mg/dL, were more likely to have Brain Natriuretic Peptide >400 pg/mL (OR 10.50, 95%CI 4.40-25.04), D-Dimer >3 µg/mL (7.51, [3.18-17.73]), and absolute lymphocyte count (ALC) <1.5 K/mcL (21.42, [7.19-63.76]). We found CRP >4.5 mg/dL and ALC <1.5 K/mcL to be 86% sensitive and 91% specific to identify MIS-C among patients screened in our population. CONCLUSIONS: We identified that elevated CRP and lymphopenia was 86% sensitive and 91% specific for identification of children with MIS-C.

Cardiac echocardiogram findings of severe acute respiratory syndrome coronavirus-2-associated multi-system inflammatory syndrome in children.

BACKGROUND: A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic. OBJECTIVES: To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children. METHODS: Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher's exact, and Wilcoxon rank sum. RESULTS: Thirty-nine children with median (interquartile range) age 7.8 (3.6-12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26-61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04). CONCLUSION: Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

Practicing What We Teach: Increasing Inhaler Use for Mild Asthma in the Pediatric Emergency Department.

INTRODUCTION: Asthma is a leading cause of pediatric emergency department (ED) visits. A metered-dose inhaler and spacer (MDI-S) device is equivalent to and more cost effective than delivery by nebulization in the ED management of mild asthma exacerbations. We aimed to increase the use of albuterol MDI-S among patients with mild asthma exacerbations using a quality improvement framework. METHODS: We evaluated albuterol use for mild asthma exacerbations between January 2019 and March 2020 in our pediatric EDs. RESULTS: Our primary outcome was the proportion of albuterol delivered through an MDI-S. Our process measure was the use of a new electronic order set. Balancing measures included ED length of stay, admission rates, and the use of intravenous magnesium. Interventions included forging multidisciplinary partnerships, revising clinical practice guidelines, establishing an electronic order set, and leading educational initiatives for clinicians. We demonstrated a center line shift of MDI-S use from 34.4% to 47.7%. The average length of stay, hospital admissions, and magnesium use were not affected by our interventions. CONCLUSION: Forging multidisciplinary partnerships, creating an electronic order set prioritizing albuterol MDI-S use, and educational initiatives led to a sustained increase in albuterol MDI-S use for mild asthma in our pediatric EDs.

Pediatric Emergency Department Discharge Instructions for Spanish-Speaking Families: Are We Getting It Right?

OBJECTIVES: Patients who speak Spanish are less likely to comply with discharge instructions, adhere to appointments, and take medications than English-speaking patients. However, adherence is improved when discharge instructions are provided in Spanish. This study was designed to assess the frequency of providing written discharge instructions in Spanish to patients who speak Spanish and request interpretation services, and to determine factors associated with receiving written discharge instructions in the preferred language in a pediatric emergency department (ED). METHODS: This was a retrospective cross-sectional study of all discharges of Spanish-speaking patients who requested an interpreter in 1 year from a large urban pediatric ED and an associated community ED. Multivariable logistic regression was used to identify patient and visit level characteristics associated with receiving written discharge instructions in Spanish. RESULTS: Sixty-one percent of 11,545 patient encounters where a Spanish interpreter was requested received written discharge instructions in Spanish. Patients aged 1 to 3 years (adjusted odds ratio [aOR], 2.87; 95% CI, 2.18-3.77) and aged 4 to 12 years (aOR, 2.06; 95% CI, 1.6-2.65), those seen without a trainee (aOR, 1.37; 95% CI, 1.25-1.5), and those with low acuity triage levels (aOR, 1.6; 95% CI, 1.29-1.97) were more likely to receive discharge instruction in Spanish. Female patients were less likely to receive Spanish discharge instructions (aOR, 0.9; 95% CI, 0.83-0.97). CONCLUSIONS: Discharged pediatric ED patients often do not receive written instructions in the preferred language. Patient and provider factors are associated with receiving written instructions in Spanish. Quality improvement efforts are needed to ensure appropriate language discharge education.

Multisystem Inflammatory Syndrome of Children: Subphenotypes, Risk Factors, Biomarkers, Cytokine Profiles, and Viral Sequencing.

OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. CONCLUSIONS: This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.

Structural and functional analysis of Ccr1l1, a Rodentia-restricted eosinophil-selective chemokine receptor homologue.

Mouse Ccr1l1 (Ccr1-like 1) encodes an orphan G-protein-coupled receptor (GPCR) with the highest homology to the inflammatory and highly promiscuous chemokine receptors Ccr1 and Ccr3 (70 and 50% amino acid identity, respectively). Ccr1l1 was first cloned in 1995, yet current knowledge of this putative chemokine receptor is limited to its gene organization and chromosomal localization. Here we report that Ccr1l1 is a Rodentia-specific gene selectively expressed in eosinophils. However, eosinophil phenotypes, development, and responsiveness to chemokines were all normal in naïve Ccr1l1 knockout mice. We demonstrate for the first time that recombinant Ccr1l1 is expressed on the plasma membrane of transfected cells and contains an extracellular N terminus and an intracellular C terminus, consistent with GPCR topology. Using receptor internalization, ß-arrestin recruitment, calcium flux, and chemotaxis assays, we excluded all 37 available mouse chemokines, including Ccr1 ligands, and two viral chemokines as Ccr1l1 ligands, and demonstrated that mouse Ccr1, but not Ccr1l1, exhibits constitutive signaling activity. However, sequence analysis and structural modeling revealed that Ccr1l1 is well equipped to act as a classical signaling GPCR, with N-terminal sulfotyrosines as the only signaling and chemokine-binding determinant absent in Ccr1l1. Hereof, we show that a sulfatable N-terminal Ccr1 Y18 residue is essential for chemotaxis and calcium responses induced by Ccl3 and Ccl9/10, but substituting the corresponding Ccr1l1 F19 residue with tyrosine failed to confer responsiveness to Ccr1 ligands. Although Ccr1l1 remains an extreme outlier in the chemokine receptor family, our study supports that it might respond to unidentified mouse chemokine ligands in eosinophil-driven immune responses.

Trends in Pediatric Poisoning-Related Emergency Department Visits: 2001-2011.

OBJECTIVES: We sought to understand the burden of pediatric poisonings on the health care system by characterizing poisoning-related emergency department (ED) visits among children on a national level. METHODS: This was a repeated cross-sectional analysis of the National Hospital Ambulatory Medical Care Survey from 2001 to 2011 of children 21 years or younger who presented to an ED. We measured annual rates of visits, trends over time, and patient and visit characteristics associated with poisoning-related ED visits using multivariable logistic regression. We also compared accidental to intentional poisonings. RESULTS: There were an estimated 713,345 ED visits per year for poisoning in children, and intentional poisoning-related visits increased over the study period (P trend < 0.001). Compared with all other ED visits, poisoning-related ED visits were more common among males (adjusted odds ratio [aOR], 1.44; 95% confidence interval [CI], 1.26-1.64) and uninsured patients (aOR, 1.26; 95% CI, 1.05-1.51). Poisoned children were more likely to arrive by ambulance (aOR, 3.38; 95% CI, 2.85-4.01) and be admitted (aOR, 1.35; 95% CI, 1.12-1.61). Compared with accidental poisonings, intentional poisonings were more common as age increased (aOR, 1.16; 95% CI, 1.13-1.92) and in children of non-Hispanic black race/ethnicity (aOR, 1.81; 95% CI, 1.12-2.93) and more likely to be associated with ambulance arrival (aOR, 1.49; 95% CI, 1.07-2.08) and hospital admission (aOR, 1.76; 95% CI, 1.25-2.48). CONCLUSIONS: Poisoning-related ED visits among children have remained stable, with significant increase in intentional ingestions from 2001 to 2011. Poisoned children, and particularly those with intentional poisonings, require more health care resources than children with other health concerns. More study is needed on circumstances leading to pediatric poisonings, so that preventive efforts can be targeted appropriately.

Repeated dermal application of the common preservative methylisothiazolinone triggers local inflammation, T cell influx, and prolonged mast cell-dependent tactile sensitivity in mice.

Occupational exposure to toxic chemicals increases the risk of developing localized provoked vulvodynia-a prevalent, yet poorly understood, chronic condition characterized by sensitivity to touch and pressure, and accumulation of mast cells in painful tissues. Here, we topically sensitized female ND4 Swiss mice to the common household and industrial preservative methylisothiazolinone (MI) and subsequently challenged them daily with MI or acetone and olive oil vehicle on the labiar skin. MI-challenged mice developed significant, persistent tactile sensitivity and long-lasting local accumulation of mast cells alongside early, transient increases in CD4+ and CD8+ T cells, eosinophils, neutrophils, and increases in pro-inflammatory cytokines. Therapeutic administration of imatinib, a c-Kit inhibitor known to inhibit mast cell survival, led to reduced mast cell accumulation and alleviated tactile genital pain. We provide the first pre-clinical evidence of dermal MI-induced mast-cell dependent pain and lay the groundwork for detailed understanding of these intersections between MI-driven immunomodulation and chronic pain.

Improvement science is a partner in basic and clinical research.

A breadth of time, effort, and resources are put into research. Improvement science is an applied science emphasizing rapid-cycle testing to learn about change and produce improvement. Its foundations lie in understanding your system, its parts and their relationships, and the psychology of change, yet the framework of improvement science is analogous to basic research. In basic research you first ask a question, then form a hypothesis based on background research. After testing this hypothesis, a researcher then draws conclusions and shares the results. In improvement science, researchers start the same, with asking a question, and then defining what is considered an improvement. Rapid-cycle tests of change are guided by subject matter experts and the people and processes involved. The data provided from these tests of change allow researchers to show improvement and share results. The success of improvement science is showcased through statistical process control charts, which inform when significant change has occurred. Improvement science can be applied across all fields of medicine; is a natural partner to basic and clinical research, as it plays a vital role in the implementation and adoption of the best evidence.

Repeated Vaginal Exposures to the Common Cosmetic and Household Preservative Methylisothiazolinone Induce Persistent, Mast Cell-Dependent Genital Pain in ND4 Mice.

A history of allergies doubles the risk of vulvodynia-a chronic pain condition of unknown etiology often accompanied by increases in numbers of vulvar mast cells. We previously established the biological plausibility of this relationship in mouse models where repeated exposures to the allergens oxazolone or dinitrofluorobenzene on the labiar skin or inside the vaginal canal of ND4 Swiss Webster outbred mice led to persistent tactile sensitivity and local increases in mast cells. In these models, depletion of mast cells alleviated pain. While exposure to cleaning chemicals has been connected to elevated vulvodynia risk, no single agent has been linked to adverse outcomes. We sensitized female mice to methylisothiazolinone (MI)-a biocide preservative ubiquitous in cosmetics and cleaners-dissolved in saline on their flanks, and subsequently challenged them with MI or saline for ten consecutive days in the vaginal canal. MI-challenged mice developed persistent tactile sensitivity, increased vaginal mast cells and eosinophils, and had higher serum Immunoglobulin E. Therapeutic and preventive intra-vaginal administration of Δ9-tetrahydrocannabinol reduced mast cell accumulation and tactile sensitivity. MI is known to cause skin and airway irritation in humans, and here we provide the first pre-clinical evidence that repeated MI exposures can also provoke allergy-driven genital pain.

Acute-Onset Flaccid Hemiparesis in a 9-Year-Old Boy With Presumed Enteroviral Infection.

In the summer and autumn of 2014, a cluster of cases of flaccid paralysis were seen in the United States related to patients infected with enterovirus D68 (EV-D68). We present here a case of acute-onset flaccid hemiparesis in a previously healthy boy with altered mental status, hypothermia, and bowel incontinence.

Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils.

Bone marrow-derived myeloid cells can accumulate within tumors and foster cancer outgrowth. Local immune-neoplastic interactions have been intensively investigated, but the contribution of the systemic host environment to tumor growth remains poorly understood. Here, we show in mice and cancer patients (n = 70) that lung adenocarcinomas increase bone stromal activity in the absence of bone metastasis. Animal studies reveal that the cancer-induced bone phenotype involves bone-resident osteocalcin-expressing (Ocn+) osteoblastic cells. These cells promote cancer by remotely supplying a distinct subset of tumor-infiltrating SiglecFhigh neutrophils, which exhibit cancer-promoting properties. Experimentally reducing Ocn+ cell numbers suppresses the neutrophil response and lung tumor outgrowth. These observations posit osteoblasts as remote regulators of lung cancer and identify SiglecFhigh neutrophils as myeloid cell effectors of the osteoblast-driven protumoral response.

Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia.

BACKGROUND: Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. Epidemiologic studies associate the risk of vulvodynia with a history of atopic disease. We used an established model of hapten-driven contact hypersensitivity to investigate the underlying mechanisms of allergy-provoked prolonged sensitivity to pressure. METHODS: We sensitized female ND4 Swiss mice to the hapten oxazolone on their flanks, and subsequently challenged them four days later with oxazolone or vehicle for ten consecutive days on the labia. We evaluated labiar sensitivity to touch, local mast cell accumulation, and hyperinnervation after ten challenges. RESULTS: Oxazolone-challenged mice developed significant tactile sensitivity that persisted for over three weeks after labiar allergen exposures ceased. Allergic sites were characterized by mast cell accumulation, sensory hyper-innervation and infiltration of regulatory CD4+CD25+FoxP3+ T cells as well as localized early increases in transcripts encoding Nerve Growth Factor and nerve-mast cell synapse marker Cell Adhesion Molecule 1. Local depletion of mast cells by intra-labiar administration of secretagogue compound 48/80 led to a reduction in both nerve density and tactile sensitivity. CONCLUSIONS: Mast cells regulate allergy-provoked persistent sensitivity to touch. Mast cell-targeted therapeutic strategies may provide novel means to manage and limit chronic pain conditions associated with atopic disease.

Hemoglobin conformation couples erythrocyte S-nitrosothiol content to O2 gradients.

It is proposed that the bond between nitric oxide (NO) and the Hb thiol Cys-beta(93) (SNOHb) is favored when hemoglobin (Hb) is in the relaxed (R, oxygenated) conformation, and that deoxygenation to tense (T) state destabilizes the SNOHb bond, allowing transfer of NO from Hb to form other (vasoactive) S-nitrosothiols (SNOs). However, it has not previously been possible to measure SNOHb without extensive Hb preparation, altering its allostery and SNO distribution. Here, we have validated an assay for SNOHb that uses carbon monoxide (CO) and cuprous chloride (CuCl)-saturated Cys. This assay is specific for SNOs and sensitive to 2-5 pmol. Uniquely, it measures the total SNO content of unmodified erythrocytes (RBCs) (SNO(RBC)), preserving Hb allostery. In room air, the ratio of SNO(RBC) to Hb in intact RBCs is stable over time, but there is a logarithmic loss of SNO(RBC) with oxyHb desaturation (slope, 0.043). This decay is accelerated by extraerythrocytic thiol (slope, 0.089; P < 0.001). SNO(RBC) stability is uncoupled from O(2) tension when Hb is locked in the R state by CO pretreatment. Also, SNO(RBC) is increased approximately 20-fold in human septic shock (P = 0.002) and the O(2)-dependent vasoactivity of RBCs is affected profoundly by SNO content in a murine lung bioassay. These data demonstrate that SNO content and O(2) saturation are tightly coupled in intact RBCs and that this coupling is likely to be of pathophysiological significance.