Improving Neonatal Intensive Care Unit Providers' Perceptions of Palliative Care through a Weekly Case-Based Discussion

Objective: The primary objective was to evaluate the efficacy of a weekly palliative care-guided, case-based discussion of high-risk infants on Neonatal Intensive Care Unit (NICU) physician (MD) and Advanced Practice Provider (APP) perceptions of pediatric palliative care (PPC). Study Design: The study setting was a level IV academic NICU in a United States midwestern children's hospital. A pre/post design was used to evaluate the effects of a weekly palliative care-guided, case-based discussion of high-risk infants on neonatology providers' (MD and APP) perspectives of palliative and end-of-life care in the NICU using a previously published survey instrument. Surveys were completed at baseline and after 12 months of implementation. Data was analyzed with a Wilcoxon Signed Rank test with significance set at p < 0.05. Results: Thirty-one providers (13 APPs and 18 MDs) completed both pre- and post-intervention surveys. Post-intervention, providers were more likely to endorse that they "are comfortable with PPC", "feel comfortable teaching PPC to trainees", "feel confident handling end-of-life care", "have time to discuss PPC", and "were satisfied with the transition to end-of-life care for their most recent patient". They also were more likely to report, "families' perception of burden is relevant when making ethical decisions", that "parents are involved in decisions regarding palliative care", and that their "institution is supportive of palliative care." (p-values < 0.05 for all). Conclusion: NICU provider perceptions of palliative care can be improved through the implementation of a case-based interdisciplinary conference that emphasizes palliative care domains in the context of Neonatal ICU care

Reducing Unnecessary Nitric Oxide Use: A Hospital-Wide, Respiratory Therapist-Driven Quality Improvement Project

BACKGROUND: We sought to evaluate the institutional use of inhaled nitric oxide (INO) and to create a pathway to reduce waste using the Institute for Healthcare Improvement's model for improvement. Our aim was to reduce the use of INO by 20% within 8 months. METHODS: This was a prospective, respiratory therapist-driven, quality improvement project. We implemented a hospital-wide INO utilization protocol that was developed by neonatology, pediatric critical care, cardiac critical care, and respiratory therapy. INO use and respiratory therapist input for protocol failures were derived from the electronic medical record and were used to generate improvement opportunities. Monthly total hospital use of INO (in hours) was used as the primary outcome measure. Median hourly use per subject (evaluated in groups of 7 subjects) was used as a secondary outcome measure. New sildenafil dosing was tabulated for pre- and post-INO weaning protocol intervention as a balancing measure. Subjects included all patients in the hospital who were given INO therapy during the specified timeframe. RESULTS: Hospital-wide total hours were reduced from 1,515 h/month to 930 h/month. This hospital-wide reduction of 39% equates to a cost-avoidance of approximately $912,000 per year based on 2018 costs of INO of$130 per hour. Median hours of INO per subject decreased from 88 h to 50 h. Sildenafil was started in 18 of 98 subjects (18%) in the pre-intervention period and in 12 of 109 subjects (11%) in the post-intervention period (P = .27). CONCLUSIONS: A hospital-wide, multi-professional initiative led to a reduction in unnecessary INO use, resulting in decreased subject exposure and associated cost avoidance

Long Range Magnetic Order and the Darwin Lagrangian

We simulate a finite system of $N$ confined electrons with inclusion of the Darwin magnetic interaction in two- and three-dimensions. The lowest energy states are located using the steepest descent quenching adapted for velocity dependent potentials. Below a critical density the ground state is a static Wigner lattice. For supercritical density the ground state has a non-zero kinetic energy. The critical density decreases with $N$ for exponential confinement but not for harmonic confinement. The lowest energy state also depends on the confinement and dimension: an antiferromagnetic cluster forms for harmonic confinement in two dimensions.Comment: 5 figure

p21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics

Mast cells are key participants in allergic diseases via activation of high-affinity IgE receptors (FcϵRI) resulting in release of proinflammatory mediators. The biochemical pathways linking IgE activation to calcium influx and cytoskeletal changes required for intracellular granule release are incompletely understood. We demonstrate, genetically, that Pak1 is required for this process. In a passive cutaneous anaphylaxis experiment, Wsh/Wsh mast cell–deficient mice locally reconstituted with Pak1−/− bone marrow–derived mast cells (BMMCs) experienced strikingly decreased allergen-induced vascular permeability compared with controls. Consistent with the in vivo phenotype, Pak1−/− BMMCs exhibited a reduction in FcϵRI-induced degranulation. Further, Pak1−/− BMMCs demonstrated diminished calcium mobilization and altered depolymerization of cortical filamentous actin (F-actin) in response to FcϵRI stimulation. These data implicate Pak1 as an essential molecular target for modulating acute mast cell responses that contribute to allergic diseases

Unexplored therapeutic opportunities in the human genome

A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development