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.

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.

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

Tau is a microtubule-associated protein (, 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 locus resulted in the identification of hot spots for activity in the 3' UTR.

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.

"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.

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

Racial disparities in pain management have been previously reported for children receiving emergency care. 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. Planned secondary analysis of RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure).

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.

Testing Pediatric Emergency Telemedicine Implementation Strategies Using Quality Improvement Methods.

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.

Developing an Interfacility Transfer Handoff Intervention: Applying the Person-Based Approach Method.

Objective: To develop an interfacility transfer handoff intervention by applying the person-based approach method.

Methods: We conducted a qualitative study that used nominal group technique (NGT) and focus groups to apply the person-based approach for intervention development. NGT methods were used to determine prioritized pediatric transfer handoff elements to design the initial intervention prototype.

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.

Allele-Selective Knockdown of MYH7 Using Antisense Oligonucleotides.

Hundreds of dominant-negative myosin mutations have been identified that lead to hypertrophic cardiomyopathy, and the biomechanical link between mutation and disease is heterogeneous across this patient population. To increase the therapeutic feasibility of treating this diverse genetic population, we investigated the ability of locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) to selectively knock down mutant myosin transcripts by targeting single-nucleotide polymorphisms (SNPs) that were found to be common in the myosin heavy chain 7 (MYH7) gene. We identified three SNPs in MYH7 and designed ASO libraries to selectively target either the reference or alternate MYH7 sequence.

Interprofessional Approach to the Sustained in a Pediatric Intensive Care Unit.

Background: Ventilator-associated pneumonia (VAP) increases morbidity, mortality, and health care costs.

Objective: To reduce the VAP rate in the pediatric/cardiac intensive care unit to fewer than 2 events per 1000 ventilator days within 2 years and to sustain a rate near 0 for the next 5 years.

Methods: An evidence-based VAP prevention bundle was developed and implemented by an interprofessional team using the Six Sigma Define, Measure, Analyze, Improve, Control methodology.

Illness Severity of Children Admitted to the PICU From Referring Emergency Departments.

Objectives: To compare patient factors and outcomes among children admitted to PICUs from referring versus children's hospital emergency departments (EDs).

Methods: Pediatric patients (<19 years old) admitted to PICUs from referring and children's hospital EDs from July 1, 2011 to June 30, 2013. We compared demographic and clinical factors, including severity of illness as measured by a recalibrated Pediatric Index of Mortality, version 2 score.

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.

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.

Design and Synthesis of a New Series of 4-Heteroarylamino-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octanes as α7 Nicotinic Receptor Agonists. 1. Development of Pharmacophore and Early Structure-Activity Relationship.

The design and synthesis of a series of quinuclidine-containing spirooxazolidines ("spiroimidates") and their utility as α7 nicotinic acetylcholine receptor partial agonists are described. Selected members of the series demonstrated excellent selectivity for α7 over the highly homologous 5-HT receptor. Modification of the N-spiroimidate heterocycle substituent led to (1S,2R,4S)-N-isoquinolin-3-yl)-4'H-4-azaspiro[bicyclo[2.

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.

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.

Tau overexpression impacts a neuroinflammation gene expression network perturbed in Alzheimer's disease.

Filamentous inclusions of the microtubule-associated protein, tau, define a variety of neurodegenerative diseases known as tauopathies, including Alzheimer's disease (AD). To better understand the role of tau-mediated effects on pathophysiology and global central nervous system function, we extensively characterized gene expression, pathology and behavior of the rTg4510 mouse model, which overexpresses a mutant form of human tau that causes Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We found that the most predominantly altered gene expression pathways in rTg4510 mice were in inflammatory processes.