Neuromuscular problems of the critically Ill neonate and child.

Acute neuromuscular disorders occasionally occur in the Pediatric Neurologic Intensive Care Unit. Many of these are primary disorders of the motor unit that may present acutely or exacerbate during an intercurrent illness. Additionally, acute neuromuscular disorders may develop during an acute systemic illness requiring intensive care management that predispose the child to another set of acute motor unit disorders. This chapter discusses acute neuromuscular crises in the infant, toddler, and adolescent, as well as neuromuscular disorders resulting from critical illness.

The Integration of Quality Improvement and Health Care Simulation: A Scoping Review.

BACKGROUND AND OBJECTIVES: Quality improvement (QI) and simulation employ complementary approaches to improve the care provided to patients. There is a significant opportunity to leverage these disciplines, yet little is known about how they are utilized in concert. The purpose of this study is to explore how QI and simulation have been used together in health care. METHODS: This scoping review includes studies published between 2015 and 2021 in 4 databases: CINAHL, Embase, PubMed, and Scopus. RESULTS: The search yielded 921 unique articles.18 articles met the inclusion criteria and specifically described QI and simulation collaborative projects. Of the 18 articles, 28% focused on improvements in patient care, 17% on educational interventions, 17% on the identification of latent safety threats (LSTs) that could have an impact on clinical care, 11% on the creation of new processes, 11% on checklist creation, and 6% on both LST identification and educational intervention. The review revealed that 61% of the included studies demonstrated a concurrent integration of simulation and QI activities, while 33% used a sequential approach. CONCLUSIONS: There is a paucity of studies detailing the robust and synergistic use of QI and simulation. The findings of this review suggest a positive impact on patient safety when QI and simulation are used in tandem. The systematic integration of these disciplines and the use of established reporting guidelines can promote patient safety in practice and in the literature.

Phase 1 Open-Label Study of Omigapil in Patients With LAMA2- or COL6-Related Dystrophy.

Background and Objectives: Omigapil is a small molecule which inhibits the GAPDH-Siah1-mediated apoptosis pathway. Apoptosis is a pathomechanism underlying the congenital muscular dystrophy subtypes LAMA2-related dystrophy (LAMA2-RD) and COL6-related dystrophy (COL6-RD). Studies of omigapil in the (dyw/dyw) LAMA2-RD mouse model demonstrated improved survival, and studies in the (dy2J/dy2J) LAMA2-RD mouse model and the (Col6a1-/-) COL6-RD mouse model demonstrated decreased apoptosis. Methods: A phase 1 open-label, sequential group, ascending oral dose, cohort study of omigapil in patients with LAMA2-RD or COL6-RD ages 5-16 years was performed (1) to establish the pharmacokinetic (PK) profile of omigapil at a range of doses, (2) to evaluate the safety and tolerability of omigapil at a range of doses, and (3) to establish the feasibility of conducting disease-relevant clinical assessments. Patients were enrolled in cohorts of size 4, with each patient receiving 4 weeks of vehicle run-in and 12 weeks of study drug (at daily doses ranging from 0.02 to 0.08 mg/kg). PK data from each cohort were analyzed before each subsequent dosing cohort was enrolled. A novel, adaptive dose-finding method (stochastic approximation with virtual observation recursion) was used to allow for dose escalation/reduction between cohorts based on PK data. Results: Twenty patients were enrolled at the NIH (LAMA2-RD: N = 10; COL6-RD: N = 10). Slightly greater than dose-proportional increases in systemic exposure to omigapil were seen at doses 0.02-0.08 mg/kg/d. The dose which achieved patient exposure within the pre-established target area under the plasma concentration-vs-time curve (AUC0-24h) range was 0.06 mg/kg/d. In general, omigapil was safe and well tolerated. No consistent changes were seen in the disease-relevant clinical assessments during the duration of the study. Discussion: This study represents the thus far only clinical trial of a therapeutic small molecule for LAMA2-RD and COL6-RD, completed with an adaptive trial design to arrive at dose adjustments. The trial met its primary end point and established that the PK profile of omigapil is suitable for further development in pediatric patients with LAMA2-RD or COL6-RD, the most common forms of congenital muscular dystrophy. While within the short duration of the study disease-relevant clinical assessments did not demonstrate significant changes, this study establishes the feasibility of performing interventional clinical trials in these rare disease patient populations. Classification of Evidence: This study provides Class IV evidence of omigapil in a dose-finding phase 1 study. Trial Registration Information: Clinical Trials NCT01805024.

Reduction of Central-line-Associated Bloodstream Infections in a Tertiary Neonatal Intensive Care Unit through Simulation Education.

Introduction: Critically ill neonates and those with complex medical conditions frequently require the use of central venous lines. Unfortunately, central line-associated bloodstream infections (CLABSIs) result in significant morbidity and mortality, and the cost and increased length of stay burden the healthcare system. Previous studies have demonstrated that standardized care bundles can decrease CLABSI rates, but achieving sustained improvement has proven difficult. Methods: All patients admitted to the Neonatal Intensive Care Unit between 2014 and 2020 who had a CVL were included in this study. First, we recorded all CLABSI events and total CVL days according to defined criteria. Then, in late 2016, we instituted simulation-based nursing training for CVL care. Results: Job Instruction Sheets were initially introduced to Neonatal Intensive Care Unit nursing staff simultaneously with one-on-one teaching sessions between instructors and bedside nurses. Intermittent performance audits and re-education for identified deficiencies did not improve the CLABSI rate per 1000 line days. After instituting simulation-based CVL training in 2016, there was a decreased rate of CLABSI events per 1000 line days sustained over time (x = 0.692). Conclusions: Standardized care bundles and Hospital-acquired Condition interactor audits were insufficient to reduce the CLABSI rate. However, combining care bundles and education with simulation-based training significantly decreased CLABSI rates. One-on-one intensive training and continued ongoing monitoring were critical to producing a sustained reduction. This experience demonstrates that supervised, interactive education combined with simulation can significantly impact patient outcomes.