Forestalling: Decreasing Super-Utilizers in the Emergency Department Using Case Management Strategies

In 2019, it was estimated there were 18 million avoidable emergency department (ED) visits, totaling $32 billion in unnecessary healthcare spending. Super-utilizers (SU), individuals that seek care in the ED 3 or more times per year, account for a disproportionately large segment of healthcare consumption and costs. These patients inefficiently access the healthcare system and often fail to get the follow-up care that could prevent them from repeat ED visits. This evidence-based project aimed to reduce unnecessary ED visits by at least 25% annually and have no use of the ED during the intervention period, by implementing social and medical care coordination case management strategies. The intent was to provide follow-up, support, and empower patients to manage their health and keep them out of the ED. This project was designed using the Blueprint for Complex Care and the IOWA model to promote quality care. The 5 A’s framework was utilized for post-discharge phone calls. The interventions included follow-up phone calls at designated intervals to ensure understanding of ED stay, confirm a post-discharge appointment with their primary care provider or specialist, evaluate comprehension of their plan of care and medications, and to assist them in identifying and accessing social or community resources. Of the ten patients enrolled for the project, two of the patients returned to the ED for care during the intervention. Both patients ended up having psychiatric issues that proved to be significant barriers for comprehension of their medical diagnoses, plan of care, and ability to manage their health. The data did elucidate reductions in ED use is possible among superutilizers, without significant psychiatric issues, using the case management interventions. Primary care providers should be aware of SU patients in their practice and arrange frequent follow-up to decrease their reliance on the ED for care

A Fluorescent Probe Identifies Active Site Ligands of Inositol Pentakisphosphate 2-Kinase

Inositol pentakisphosphate 2-kinase catalyzes the phosphorylation of the axial 2-OH of myo-inositol 1,3,4,5,6-pentakisphosphate for de novo synthesis of myo-inositol hexakisphosphate. Disruption of inositol pentakisphosphate 2-kinase profoundly influences cellular processes; from nuclear mRNA export and phosphate homeostasis in yeast and plants, to establishment of left-right asymmetry in zebra fish. We elaborate an active site fluorescent probe that allows high throughput screening of Arabidopsis inositol pentakisphosphate 2-kinase. We show that the probe has a binding constant comparable to the Km values of inositol phosphate substrates of this enzyme, and can be used to prospect for novel substrates and inhibitors of inositol phosphate kinases. We identify several micromolar Ki inhibitors and validate this approach by solving the crystal structure of protein in complex with purpurogallin. We additionally solve structures of protein in complexes with epimeric higher inositol phosphates. This probe may find utility in characterization of a wide family of inositol phosphate kinases

Ligands of Inositol Polyphosphate Binding Proteins

In plants, cytosolic and organellar inositol polyphosphate (InsP) molecules are involved in multiple stress response pathways, such as drought tolerance and herbivory defence. The turnover and function of InsPs in vivo depend on enzymes including inositol phosphate kinases (IPKs) and phosphatases. InsP receptor proteins co-ordinate cellular responses dependent on the pool of InsPs present. Many IPKs localize to the nucleus, including AtIPK1 which is responsible for the synthesis of phytic acid, the implicated regulatory ligand of an mRNA transporter complex, a phytohormone co-receptor complex and precursor molecule to a subclass of InsPs, inositol pyrophosphates (PP-InsPs). Despite implications of IPKs in nuclear regulatory roles, these have not been described in plants. The primary research aim was to investigate a nuclear role of AtIPK1 through DNA binding assays (Chapter 2) and structure-function studies (Chapter 3). SPX domains have recently been identified as PP-InsP ligand receptors which mediate plant phosphate homeostasis. A secondary aim of this project was to characterize a subset of Arabidopsis SPX domain proteins (AtSPX1, AtSPX3, AtPHT5;1), with a particular focus on substrate discrimination towards InsPs and PP-InsPs. To this end protein production, ligand-binding assays and structure-function studies were attempted (Chapter 4). This thesis presents evidence for novel DNA binding of AtIPK1 and AtSPX1, whereby DNA binding activity is regulated by InsP titrations. In the application of in silico analyses, potential DNA binding sites were identified whilst low structural homology between these proteins and known DNA binding proteins were observed. A novel structure of wildtype apo AtIPK1 was solved lending new insights into conformational changes upon ligand binding. Additionally, AtSPX1 ligand binding was studied showing subtle differences of InsP preference in the absence of DNA interaction partner. Thus, demonstrating how InsP-binding proteins may exhibit additional regulatory functions which depend upon specific InsP substrate interactions

Improving Door-To-Decision Time for Patients on Warfarin Presenting With Acute Ischaemic Stroke

Stroke is a leading cause of disability and death in Ireland, and a vital component in the management of stroke is a timely response. Recommendations have been made to achieve door-to-treatment times of less than 60 minutes. A public hospital in Dublin experienced delays in this process, particularly in regard to the attainment of International Normalised Ratio blood results for patients on Warfarin. Of the seven patients on Warfarin who presented during a four-month period, none received thrombolysis therapy, with an average of 88 minutes wait for availability of International Normalised Ratio results. Through guidance from the Lean Six Sigma model and the use of multiple quality improvement tools, a plan was made to reduce door-to-decision times for Warfarin patients presenting with an acute ischaemic stroke, through implementation of two improvements. The first is to notify the laboratory of the urgency of these results, and the second is the hand delivery of the samples to the laboratory. The aim is to reduce the time it takes to receive these blood results to less than 45 minutes. Following implementation, continuous evaluation will be imperative to drive and maintain the improvement.</p

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7