Protocol-Driven Initiation and Weaning of High-Flow Nasal Cannula for Patients With Bronchiolitis: A Quality Improvement Initiative.

OBJECTIVES: Bronchiolitis is the most common cause for nonelective infant hospitalization in the United States with increasing utilization of high-flow nasal cannula (HFNC). We standardized initiation and weaning of HFNC for bronchiolitis and quantified the impact on outcomes. Our specific aim was to reduce hospital and ICU length of stay (LOS) by 10% between two bronchiolitis seasons after implementation. DESIGN: A quality improvement (QI) project using statistical process control methodology. SETTING: Tertiary-care children's hospital with 24 PICU and 48 acute care pediatric beds. PATIENTS: Children less than 24 months old with bronchiolitis without other respiratory diagnoses or underlying cardiac, respiratory, or neuromuscular disorders between December 2017 and November 2018 (baseline), and December 2018 and February 2020 (postintervention). INTERVENTIONS: Interventions included development of an HFNC protocol with initiation and weaning guidelines, modification of protocol and respiratory assessment classification, education, and QI rounds with a focus on efficient HFNC weaning, transfer, and/or discharge. MEASUREMENTS AND MAIN RESULTS: A total of 223 children were included (96 baseline and 127 postintervention). The primary outcome metric, average LOS per patient, decreased from 4.0 to 2.8 days, and the average ICU LOS per patient decreased from 2.8 to 1.9 days. The secondary outcome metric, average HFNC treatment hours per patient, decreased from 44.0 to 36.3 hours. The primary and secondary outcomes met criteria for special cause variation. Balancing measures included ICU readmission rates, 30-day readmission rates, and adverse events, which were not different between the two periods. CONCLUSIONS: A standardized protocol for HFNC management for patients with bronchiolitis was associated with decreased hospital and ICU LOS, less time on HFNC, and no difference in readmissions or adverse events.

"Good Catch, Kiddo"-Enhancing Patient Safety in the Pediatric Emergency Department Through Simulation.

OBJECTIVES: Adverse events that affect patient safety are a significant concern in pediatrics. Increasing situational awareness, identifying errors and near misses, and reporting them using organizational incident reporting systems enables mitigation of harm. METHODS: We designed and tested a brief, interactive, and easily replicable simulation activity for medical students, and emergency medicine interns and pediatric interns to strengthen their skills and enhance their self-efficacy in identifying and reporting patient safety hazards. Hazards fell into the categories of situational safety, patient identification and privacy, infection prevention, treatment errors, and issues with electronic health records (EHRs). RESULTS: The simulation training significantly increased the self-efficacy of medical students and interns in identifying and reporting patient safety hazards. Learners were very satisfied with the simulation training, successfully recognized key patient safety hazards, provided feedback to improve the training, and improved their ability to report hazards through organizational incident reporting systems. Patient safety hazards associated with patient misidentification were recognized most frequently, whereas safety hazards associated with EHRs were missed with the greatest frequency. CONCLUSIONS: The simulation training enabled learners to identify hazards and near misses and enhanced their ability to report hazards through organizational incident reporting systems. Learners at all levels of training identified safety hazards at comparable rates, which demonstrates the role that trainees play in critically observing clinical settings with fresh eyes and identifying and reporting patient safety hazards. Interventions to promote patient safety need to prioritize building situational awareness of potential hazards associated with EHR use.

Testing Pediatric Emergency Telemedicine Implementation Strategies Using Quality Improvement Methods.

Background: Despite the recognized benefits of telemedicine use for pediatric emergency consultations, there are barriers to the widespread uptake of this technology. Quality improvement methods can be used to rapidly test implementation strategies. Our objective was to test telemedicine implementation strategies in real-world application using quality improvement methods. Our quality improvement aim was to achieve high rates of telemedicine use for pediatric transfer consultations. Methods: A multidisciplinary multisite improvement team identified that key drivers of increasing telemedicine use included telemedicine resource awareness, streamlined telemedicine workflow, provider buy-in, and data transparency. Interventions focused on telemedicine trainings, disseminating telemedicine uptake data, telemedicine reminders, telemedicine test calls, and preparing for telemedicine use for every transfer consultation. The outcome measure was percentage of pediatric emergency transfer consultations that used telemedicine. The balancing measure was time (minutes) from the initial transfer center call to completion of the consultation. Results: Multiple plan-do-study-act cycles were associated with special cause variation, with an upward shift in mean percentage of telemedicine use from 5% to 22%. Time from initial call to consultation completion remained unchanged. Conclusion: Our study supports the use of quality improvement methods to test telemedicine implementation strategies for pediatric telemedicine emergency consultations.

Risk Stratification and Personal Protective Equipment Use in Pediatric Endoscopy During the Coronavirus Disease 2019 Outbreak: A Single-center Protocol.

SARS-CoV-2, the novel coronavirus causing coronavirus disease 2019 (COVID-19), is now a global pandemic. Human-to-human transmission has been documented to occur through respiratory secretions, feces, aerosols, and contaminated environmental surfaces. Pediatric patients present a unique challenge as they may have minimal symptoms and yet transmit disease. Endoscopists face risk for infection with viruses like SARS-CoV-2, as the aerosol generating nature of endoscopy diffuses respiratory disease that can be spread via an airborne and droplet route. We describe our center's methodology for pediatric patient risk stratification to facilitate responsible use of endoscopic resources during this crisis. We also describe our recommendations for use of personal protective equipment by endoscopists, with the goal of ensuring the safety of ourselves, our anesthesiology and endoscopy staff, and our patients.

Interprofessional/interdisciplinary teamwork during the early COVID-19 pandemic: experience from a children's hospital within an academic health center.

The COVID-19 pandemic has created multiple, complex and intense demands on hospitals, including the need for surge planning in the many locations outside epicenters such as northern Italy or New York City. We here describe such surge planning in an Academic Health Center that encompasses a children's hospital. Interprofessional teams from every aspect of inpatient care and hospital operations worked to prepare for a COVID-19 surge. In so doing, they successfully innovated ways to integrate pediatric and adult care and maximize bed capacity. The success of this intense collaborative effort offers an opportunity for ongoing teamwork to enhance efficient, effective, and high-quality patient care.

Racial and Ethnic Disparities in Parental Refusal of Consent in a Large, Multisite Pediatric Critical Care Clinical Trial.

OBJECTIVE: To evaluate whether race or ethnicity was independently associated with parental refusal of consent for their child's participation in a multisite pediatric critical care clinical trial. STUDY DESIGN: We performed a secondary analyses of data from Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE), a 31-center cluster randomized trial of sedation management in critically ill children with acute respiratory failure supported on mechanical ventilation. Multivariable logistic regression modeling estimated associations between patient race and ethnicity and parental refusal of study consent. RESULT: Among the 3438 children meeting enrollment criteria and approached for consent, 2954 had documented race/ethnicity of non-Hispanic White (White), non-Hispanic Black (Black), or Hispanic of any race. Inability to approach for consent was more common for parents of Black (19.5%) compared with White (11.7%) or Hispanic children (13.2%). Among those offered consent, parents of Black (29.5%) and Hispanic children (25.9%) more frequently refused consent than parents of White children (18.2%, P < .0167 for each). Compared with parents of White children, parents of Black (OR 2.15, 95% CI 1.56-2.95, P < .001) and Hispanic (OR 1.44, 95% CI 1.10-1.88, P = .01) children were more likely to refuse consent. Parents of children offered participation in the intervention arm were more likely to refuse consent than parents in the control arm (OR 2.15, 95% CI 1.37-3.36, P < .001). CONCLUSIONS: Parents of Black and Hispanic children were less likely to be approached for, and more frequently declined consent for, their child's participation in a multisite critical care clinical trial. Ameliorating this racial disparity may improve the validity and generalizability of study findings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00814099.

Development of spiroguanidine-derived α7 neuronal nicotinic receptor partial agonists.

We describe the synthesis of quinuclidine-containing spiroguanidines and their utility as α7 neuronal nicotinic acetylcholine receptor (nAChR) partial agonists. The convergent synthetic route developed for this study allowed for rapid SAR investigation and provided access to a structurally diverse set of analogs. A potent and selective α7 nAChR partial agonist, N-(6-methyl-1,3-benzoxazol-2-yl)-3',5'-dihydro-4-azaspiro[bicyclo[2.2.2]octane-2,4'-imidazole]-2'-amine (BMS-910731, 16), was identified. This compound induced immediate early genes c-fos and Arc in a preclinical rodent model of α7 nAChR-derived cellular activation and plasticity. Importantly, the ability to incorporate selectivity for the α7 nACh receptor over the 5-HT3A receptor in this series suggested a significant difference in steric requirements between the two receptors.

The Association Between Insurance and Transfer of Noninjured Children From Emergency Departments.

STUDY OBJECTIVE: Among children requiring hospital admission or transfer, we seek to determine whether insurance is associated with the decision to either admit locally or transfer to another hospital. METHODS: This cross-sectional study used Healthcare Cost and Utilization Project 2012 Nationwide Emergency Department Sample. Pediatric patients receiving care in emergency departments (EDs) who were either admitted or transferred were included. Clinical Classifications Software was used to categorize patients into noninjury diagnostic cohorts. Multivariable logistic regression models adjusting for potential confounders, including severity of illness and comorbidities, and incorporating nationally representative weights were used to determine the association between insurance and the odds of transfer relative to admission. RESULTS: A total of 240,620 noninjury pediatric ED events met inclusion criteria. Patient and hospital characteristics, including older age and nonteaching hospitals, were associated with greater odds of transfer relative to admission. Patients who were uninsured or had self-pay had higher odds of transfer (odds ratio [OR] 3.84; 95% confidence interval [CI] 2.08 to 7.09) relative to admission compared with those with private insurance. Uninsured and self-pay patients also had higher odds of transfer across all 13 diagnostic categories, with ORs ranging from 2.96 to 12.00. Patients with Medicaid (OR 1.05; 95% CI 0.90 to 1.22) and other insurances (OR 1.14; 95% CI 0.87 to 1.48) had similar odds of transfer compared with patients with private insurance. CONCLUSION: Children without insurance and those considered as having self-pay are more likely to be transferred to another hospital than to be admitted for inpatient care within the same receiving hospital compared with children with private insurance. This study reinforces ongoing concerns about disparities in the provision of pediatric ED and inpatient care.

Impact of Telemedicine on Severity of Illness and Outcomes Among Children Transferred From Referring Emergency Departments to a Children's Hospital PICU.

OBJECTIVES: To compare the severity of illness and outcomes among children admitted to a children's hospital PICU from referring emergency departments with and without access to a pediatric critical care telemedicine program. DESIGN: Retrospective cohort study. SETTING: Tertiary academic children's hospital PICU. PATIENTS: Pediatric patients admitted directly to the PICU from referring emergency departments between 2010 and 2014. INTERVENTIONS: None. MEASUREMENTS: Demographic factors, severity of illness, and clinical outcomes among children receiving care in emergency departments with and without access to pediatric telemedicine, as well as a subcohort of children admitted from emergency departments before and after the implementation of telemedicine. MAIN RESULTS: Five hundred eighty-two patients from 15 emergency departments with telemedicine and 524 patients from 60 emergency departments without telemedicine were transferred and admitted to the PICU. Children admitted from emergency departments using telemedicine were younger (5.6 vs 6.9 yr; p< 0.001) and less sick (Pediatric Risk of Mortality III score, 3.2 vs 4.0; p < 0.05) at admission to the PICU compared with children admitted from emergency departments without telemedicine. Among transfers from emergency departments that established telemedicine programs during the study period, children arrived significantly less sick (mean Pediatric Risk of Mortality III scores, 1.2 units lower; p = 0.03) after the implementation of telemedicine (n = 43) than before the implementation of telemedicine (n = 95). The observed-to-expected mortality ratios of posttelemedicine, pretelemedicine, and no-telemedicine cohorts were 0.81 (95% CI, 0.53-1.09), 1.07 (95% CI, 0.53-1.60), and 1.02 (95% CI, 0.71-1.33), respectively. CONCLUSIONS: The implementation of a telemedicine program designed to assist in the care of seriously ill children receiving care in referring emergency departments was associated with lower illness severity at admission to the PICU. This study contributes to the body of evidence that pediatric critical care telemedicine programs assist referring emergency departments in the care of critically ill children and could result in improved clinical outcomes.

Pediatric super-refractory status epilepticus treated with allopregnanolone.

Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ-aminobutyric acid (GABA)A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Here we describe the use of allopregnanolone in 2 pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children.

Feasibility of "Symptom Discovery," a Longitudinal and Comprehensive Data Collection Tool During COVID-19.

There are few patient- or public-facing tools for longitudinal and comprehensive symptom assessment, especially when faced with an uncharacterized condition such as COVID-19 or a chronic condition in which symptoms have not been adequately specified. To address this need, we developed the Symptom Discovery mobile application and tested its feasibility with the US public early in the COVID-19 pandemic. Although there were challenges, results showed feasibility and acceptance.

Discovery of (S,E)-3-(2-fluorophenyl)-N-(1-(3-(pyridin-3-yloxy)phenyl)ethyl)-acrylamide as a potent and efficacious KCNQ2 (Kv7.2) opener for the treatment of neuropathic pain.

Acrylamide (S)-6, a potent and efficacious KCNQ2 (Kv7.2) opener, demonstrated significant activity in two models of neuropathic pain and in the formalin test, suggesting that KCNQ2 openers may be useful in the treatment of neuropathic pain including diabetic neuropathy.

Results of phase II pharmacokinetic study of levetiracetam for prevention of post-traumatic epilepsy.

Levetiracetam (LEV) has antiepileptogenic effects in animals and is a candidate for prevention of epilepsy after traumatic brain injury. Pharmacokinetics of LEV in TBI patients was unknown. We report pharmacokinetics of TBI subjects≥6years with high PTE risk treated with LEV 55mg/kg/day orally, nasogastrically or intravenously for 30days starting ≤8h after injury in a phase II safety and pharmacokinetic study. Forty-one subjects (26 adults and 15 children) were randomized to PK studies on treatment days 3 and 30. Thirty-six out of forty-one randomized subjects underwent PK study on treatment day 3, and 24/41 subjects underwent PK study on day 30. On day 3, mean T(max) was 2.2h, C(max) was 60.2µg/ml and AUC was 403.7µg/h/ml. T(max) was longer in the elderly than in children and non-elderly adults (5.96h vs. 1.5h and 1.8h; p=0.0001). AUC was non-significantly lower in children compared with adults and the elderly (317.4µg/h/ml vs. 461.4µg/h/ml and 450.2µg/h/ml; p=0.08). C(max) trended higher in i.v.- versus tablet- or n.g.-treated subjects (78.4µg/ml vs. 59µg/ml and 48.2µg/ml; p=0.07). AUC of n.g. and i.v. administrations was 79% and 88% of AUC of oral administration. There were no significant PK differences between days 3 and 30. Treatment of TBI patients with high PTE risk with 55mg/kg/day LEV, a dose with antiepileptogenic effect in animals, results in plasma LEV levels comparable to those in animal studies.

Identification and characterization of a MAPT-targeting locked nucleic acid antisense oligonucleotide therapeutic for tauopathies.

Tau is a microtubule-associated protein (MAPT, tau) implicated in the pathogenesis of tauopathies, a spectrum of neurodegenerative disorders characterized by accumulation of hyperphosphorylated, aggregated tau. Because tau pathology can be distinct across diseases, a pragmatic therapeutic approach may be to intervene at the level of the tau transcript, as it makes no assumptions to mechanisms of tau toxicity. Here we performed a large library screen of locked-nucleic-acid (LNA)-modified antisense oligonucleotides (ASOs), where careful tiling of the MAPT locus resulted in the identification of hot spots for activity in the 3' UTR. Further modifications to the LNA design resulted in the generation of ASO-001933, which selectively and potently reduces tau in primary cultures from hTau mice, monkey, and human neurons. ASO-001933 was well tolerated and produced a robust, long-lasting reduction in tau protein in both mouse and cynomolgus monkey brain. In monkey, tau protein reduction was maintained in brain for 20 weeks post injection and corresponded with tau protein reduction in the cerebrospinal fluid (CSF). Our results demonstrate that LNA-ASOs exhibit excellent drug-like properties and sustained efficacy likely translating to infrequent, intrathecal dosing in patients. These data further support the development of LNA-ASOs against tau for the treatment of tauopathies.

Benchmarking, public reporting, and pay-for-performance: a mixed-methods survey of California pediatric intensive care unit medical directors.

OBJECTIVES: We sought to assess the attitudes of pediatric intensive care unit medical directors in California regarding the need for, the validity of, and the potential impact of benchmarking, public reporting, and pay-for-performance on pediatric critical care. DESIGN: Cross-sectional survey. SETTING: Pediatric intensive care units in California. SUBJECTS: Medical directors of pediatric intensive care units. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Self-administered questionnaire and a semi-structured phone interview from 16 pediatric intensive care unit medical directors. All data were anonymized before review. Standard methods for identifying and agreeing on themes in transcribed interviews were applied. Seventy-three percent of California pediatric intensive care unit medical directors agree that benchmarking improves patient outcomes but are undecided whether public reporting and pay-for-performance improve healthcare quality. They are wary of the validity of data used to generate these performance measures and are discouraged by the time and costs required to collect data for standard performance outcomes (severity-adjusted pediatric intensive care unit mortality). Leadership opinions appear potentially "dynamic" in multiple domains and across each of the measures assessed. CONCLUSIONS: Pediatric intensive care unit medical directors sometimes express contradictory opinions about the merits of shared benchmarking efforts and express concerns across a range of logistic, methodological, and policy issues. These findings raise fundamental questions about how to create clinical performance standards that facilitate quality improvement in the face of a seriously divided constituency. Further, we propose that pediatric intensive care unit medical directors play more active roles in the development, implementation, and communication of shared state-wide data collection.

Improving Pediatric Resident Safety Event Reporting Using Quality Improvement Methods.

BACKGROUND AND OBJECTIVES: Safety event reporting systems facilitate identification of system-level targets to improve patient safety. Resident physicians report few safety events despite their role as frontline providers and the frequent occurrence of events. The objective of this study is to increase the number of pediatric resident safety event submissions from <1 to 4 submissions per 14-day period within 12 months. METHODS: We conducted an iterative quality improvement process with 39 pediatric residents at a children's hospital. Interventions focused on 4 key drivers: user-friendly event submission process, resident buy-in, nonpunitive safety culture, and data transparency. The primary outcome measure of number of pediatric resident event submissions was analyzed by using statistical process control. Balancing measures included time from submission to feedback, duplicate submissions, and nonevent submissions. As a control, the primary outcome measure was monitored for nonpediatric residents during the same period. RESULTS: The mean number of pediatric resident event submissions increased from 0.9 to 5.7 submissions per 14 days. Impactful interventions included a designated space in the resident workroom to list safety events to submit, monthly project updates, and an interresident competition. There were no duplicate submissions or nonevent submissions in the postintervention period. Time to feedback in the postintervention period had both upward and downward shifts, with >8 consecutive points above and below the baseline period's centerline. The control group showed no sustained change in event submissions. CONCLUSIONS: Our improvement process was associated with significant increase in pediatric resident safety event submissions without an increase in the number of submissions categorized as duplicates or nonevents.

Association of Race and Ethnicity with Sedation Management in Pediatric Intensive Care.

Rationale: Racial disparities in pain management have been previously reported for children receiving emergency care.Objectives: To determine whether patient race or ethnicity is associated with the broader goal of pain management and sedation among pediatric patients mechanically ventilated for acute respiratory failure.Methods: Planned secondary analysis of RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure). RESTORE, a cluster-randomized clinical trial conducted in 31 U.S. pediatric intensive care units, compared protocolized sedation management (intervention arm) with usual care (control arm). Participants included 2,271 children identified as non-Hispanic white (white, n = 1,233), non-Hispanic Black (Black, n = 502), or Hispanic of any race (Hispanic, n = 536).Results: Within each treatment arm, neither opioid nor benzodiazepine selection, nor cumulative dosing, differed significantly among race and ethnicity groups. Black patients experienced fewer days with an episode of pain (compared with white patients in the control arm and with Hispanic patients in the intervention arm) and experienced less iatrogenic withdrawal syndrome (compared with white patients in either arm or with Hispanic patients in the intervention arm). The percentage of days awake and calm while intubated was not significantly different in pairwise comparisons by race and ethnicity groups in either the control arm (median: white, 75%; Black, 71%; Hispanic, 75%) or the intervention arm (white, 86%; Black, 88%; Hispanic, 85%).Conclusions: Across multiple measures, our study found scattered differences in sedation management among critically ill Black, Hispanic, and white children that did not consistently favor any group. However, racial disparities related to implicit bias cannot be completely ruled out.Clinical trial registered with clinicaltrials.gov (NCT00814099).