MEDICA@MUSC (Medical University of South Carolina)
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Telehealth Inclusion Within the Personal Care Home Setting: The Creation of a Telehealth Appointment Checklist for Use by Personal Care Physicians, Healthcare Providers, and Residents
Get PDFThis study was conducted in the personal care home section of a continuing care retirement community with physicians, nurses, a physician assistant, personal care medication technicians, and personal care residents to understand what is needed to conduct a successful telehealth appointment within a personal care home. Telehealth appointment success was found to be possible when healthcare providers and consumers were aware of the type of appointment being conducted, proper training occurred, and resident and staff needs, and concerns were discussed. There were barriers to telehealth inclusion within the personal care home setting such as resident cognition and participation, but overall, telehealth was seen more as a benefit than a deficit
Pharmacokinetic Optimization of Peptides and Small Molecules
No full textPharmacokinetics (PK) is the study of how the body interacts with xenobiotics, encompassing the kinetics of absorption, distribution, metabolism, excretion, and toxicity (ADMET). The ADMET properties of chemical entities play a pivotal role in drug discovery and development. Drugs of high quality should not only have sufficient affinity, selectivity, and potency, but must also possess suitable ADMET properties at a therapeutic dose. The drug failure rate is high, with less than 10% of drug candidates making it to the market after reaching Phase I clinical trials. PK issues are the most common reason for drug failure, often due to unexpected toxicity. As such, special emphasis should be placed on PK optimization in early-stage drug discovery. This dissertation reviews and implements tools used to optimize peptide and small molecule drug candidates. In aim 1, we used non-natural amino acids and a specialized ethylene-vinyl acetate (EVA) delivery system to optimize the PK of a kappa opioid receptor agonist (KOA) peptide, CR665. In doing so, we discovered TP-2021, a highly potent KOA (EC50 = 52 pM) with profound selectivity and anti-pruritic activity. Prototype EVA polymer implants were able to sustain supratherapeutic plasma concentrations of TP-2021 in a mouse model of chronic pruritus for up to four months. IND-enabling studies are ongoing. In aim 2, we elucidated the cellular and mechanisms of MEK1-inhibitor induced cardiotoxicity. Trametinib-treated animals experienced a decline in cardiac function. Transcriptomic and iPathway analysis identified IL-6 as an activator of PI3K/AKT and JAK/STAT signaling pathways, with downstream changes in genes associated with hypertrophy, cell survival, mitochondrial biogenesis, mitophagy, and oxidative stress. Key histological changes included a loss of cardiomyocyte apelin receptor expression, connexin-43 mislocalization, extracellular matrix remodeling, and, in 23% of cases, myocardial calcification and vacuolization. Additionally, FDA-approved MEK1 inhibitors block hERG, putting patients at risk for life threatening arrhythmias. Harnessed with this information, we employed a novel machine learning-based workflow to design MEK1 inhibitors with improved pharmacokinetics. Two nanomolar range candidates devoid of hERG and cytochrome P450 (CYP) interactions were identified and are undergoing further in vivo testing. Insights from this work may be replicated to design safer drug candidates
Does a Decision Support Tool Change the Rate of Kangaroo Care in the NICU?
No full textKangaroo Care (KC), the act of holding an infant in direct skin-to-skin contact against the chest of the person holding the infant has been studied primarily to highlight the benefits it provides to infants, especially premature infants. Implementation studies for KC have been limited, leaving many gaps for researchers to explore related to its practice in the neonatal intensive care unit (NICU). This dissertation is a compendium of three manuscripts that begin to explore further details about KC implementation in the NICU. The first is a realist review that explores KC implementation in NICUs by comparing the documents that describe how and when KC is performed. The second manuscript is a realist review that begins to describe KC reach, adoption, implementation, and maintenance in the NICU. The third manuscript details the results of a multi-method study that evaluates the reach of KC within a Level IV NICU and the effects of implementing a decision support tool on the reach of KC. KC offers promising benefits for infants that can help to mitigate complications related to NICU hospitalization. This dissertation highlights research gaps in KC that can be further studied to increase the amount of KC infants receive for better outcomes
The Role of STAT3 Signaling in Pancreatic Stromal Fibroblasts in Establishing an Immunosuppressive Tumor Microenvironment
No full textPancreatic Ductal Adenocarcinoma (PDAC) is associated with a desmoplastic stroma that can contribute to its recalcitrance to therapy. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types within the PDAC stroma; yet, their contribution to PDAC growth and development remain unclear. Targeting CAFs to improve PDAC therapeutic treatment is thought to be an incredibly promising strategy, however; studies have shown both tumor-promoting and tumor-limiting activities associated with PDAC CAFs. Therefore, understanding specific tumor-promoting pathways in CAFs is essential for developing better stromal targeting therapies. STAT3 is a transcription factor activates both cell survival and proliferation programs as well as immune modulating cytokines and chemokines. In PDAC, STAT3 is often aberrantly expressed and known to be a tumor driver within the epithelium, however, its stromal specific function in PDAC has yet to be elucidated. We hypothesized that STAT3 signaling in pancreatic CAFs contributes to the immunosuppressive and fibrotic stroma observed with disease progression. Using two different mouse models of PDAC, we investigate how loss of STAT3 in CAFs influences tumor growth and the tumor microenvironment (TME). Deletion of STAT3 in CAFs not only slows tumor progression and increases survival, but re-shapes the characteristic immunosuppressive TME by decreasing M2 macrophages and increasing CD8+ T cells. Mechanistically, we show that loss of the tumor suppressor PTEN in pancreatic CAFs leads to an increase in STAT3 phosphorylation. Additionally, increased STAT3 phosphorylation in pancreatic CAFs promotes secretion of CXCL1. Inhibition of CXCL1 signaling inhibits M2 polarization in vitro. The results in this thesis provide direct genetic evidence for the role of STAT3 in CAFs in promoting tumor progression and an immunosuppressive TME, and a potential mechanism by which CAFs regulate these activities
Ambulatory Telehealth Approaches During COVID-19: Small Wins, Big Wins, and Some Challenges
No full text1.An academic medical center in the Southeast US had over 10 years of telehealth experience and 80+ telehealth service lines prior to COVID-19. 2.To ensure access to care during COVID-19 and meet new demands, health system leaders and providers had to rapidly redesign how care was delivered. 3.Within the first 3 weeks of the pandemic, the health system increased the percentage of ambulatory telehealth visits from 1% of all visits to 66%.https://medica-musc.researchcommons.org/posters/1027/thumbnail.jp
Waring Library Society Newsletter, Summer 2022
Get PDFThis Bicentennial Edition of the Waring Library Society Newsletter gives a peak into what is to come as MUSC approaches its Bicentennial in 2024. This issue features reflections on the origin and impact of the Medical Society by WLS Vice Chair and President Elect, Dr. Robert Ball; an exploration of the areas of MUSC’s past needing illumination by Dr. Brian Fors; a glimpse of the Bicentennial committees, their guiding principles, and goals; more details on the Bicentennial hires that will help with the commemoration; an overview of the approved renovation project for the Waring Historical Library; and highlights of recent professional achievements of the Waring Library staff.https://medica-musc.researchcommons.org/wls-newsletters/1002/thumbnail.jp
Streamlining Surgical Safety Surveillance & Research in OR Settings Through Artificial Intelligence
No full textSurgical technology continues to improve patient outcomes, but also introduces novel challenges and risks. The increasing complexity of surgical technology leads to workflow disruptions (FD), which are deviations from the expected operation progression. The following adverse outcomes result from high FD rates: increased patient mortality, procedure duration, OR member stress, perceived workload, and surgical errors.
Through collaboration with Catchpole lab (MUSC) and Cohen lab (Cedars-Sinai), we have access to a dataset of several hundred surgical cases with flow disruptions that were transcribed by trained observers in the OR. As part of our first aim, we present software, READ-TV (Research & Exploratory Analysis Driven Time-data Visualization), to visualize flow disruption data. Our second aim proves the utility of AI, specifically transformers, to detect causally related flow disruption cascades from disruption narratives and timings. Our third aim diverges from flow disruption data to present Red Flag/Blue Flag, X-AI (eXplainable-AI) software. Red Flag/Blue Flag enables researchers to analyze how a pervasive neural network model used throughout clinical NLP (natural language processing) determines binary classifications. We present the X-AI capability of Red Flag/Blue Flag on a neural network that was trained from 11,000 physician-authored operative notes to detect surgical device & instrument misadventures
Increasing Occupational Justice in Aviation Travel Among Travelers with Spinal Cord Injuries/Disorders (SCI/D)
Get PDFNeeds Assessment for Community Health Center in Cantel Guatemala
Get PDFBackground: Implementation of a medical clinic is part of the strategic plan for Colegio Mark, a primary and secondary school in Cantel, Guatemala with a 41-year relationship with Colonial Presbyterian Church in Kansas City, Missouri. Due to resource constraints, prioritization of top health concerns and implementation of targeted solutions is key. The aim of this needs assessment is to determine how best to improve health outcomes in Cantel. Methods: Information was collected through 17 qualitative interviews, then analyzed through an affinity diagram with strengths, weakness, opportunities, and threats (SWOT analysis) as the categories. The findings were plotted on an impact versus effort matrix to determine which initiatives to prioritize. Conclusion: Respondents’ information demonstrated that a mere medical clinic is insufficient to address the pervasive health issues facing the Cantel area. Education emerged as the key component and becomes the cornerstone initiative for a community health center that will bridge the gap between the school and the broader community. The indelible mark of this health center will be combining preventive health education with reactive medical care including diagnostic tools, pharmacy, and clinicians