MEDICA@MUSC (Medical University of South Carolina)
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Development and Evaluation of a Training Program to Increase Caregiver Understanding of TheraBracelet
No full textTheraBracelet, a novel neurorehabilitation device, has previously been used with adult stroke patients to facilitate motor recovery. A training program was created to educate therapists about the device and proper usage, to facilitate correct usage during therapy sessions. TheraBracelet is currently being used in a case study in which the device was used for 2 years by a child with cerebral palsy, with hopes to expand this trial. This has created a need to develop a training program for the caregivers of children who may use TheraBracelet in the future. An asynchronous training program was created and utilized by 11 members of the Charleston community, ranging from 25 – 47 years old. Training effectiveness was evaluated using a pre and post module Likert scale survey, within module knowledge checks, and an in-person session, in which the caregiver was asked to demonstrate how to properly set-up and utilize the device. The average score of the within module knowledge checks were 82% and 84%. All learners scored 100% on the in-person knowledge evaluation and felt they could confidently assist their children in utilizing TheraBracelet in daily life
Exploring Patterns in Worksite Healthcare: An Exploratory Analysis of Worksite Healthcare Utilization and Costs
No full textBackground: In the evolving healthcare landscape, traditional models face challenges in accessibility, cost-effectiveness, and efficiency. Employer worksite clinics have emerged as innovative solutions, providing convenient access to healthcare services for employees. However, empirical evidence on their effectiveness remains limited.
Methods: This research conducted an exploratory data analysis (EDA) of claims data from the Merative® MarketScan Commercial Claims and Encounters Database. The study examined healthcare utilization, cost patterns, and quality indicators at worksite clinics, focusing on commercially insured adults engaged in the workforce. Descriptive statistics and data categorization methods were employed to explore patient demographics, healthcare service types, and financial implications.
Results: Analysis revealed that worksite clinics primarily serve a middle-aged demographic, predominantly for preventive care and routine examinations. Healthcare utilization and cost patterns indicated that these clinics could offer cost-effective care, especially for common conditions such as type 2 diabetes mellitus and acute sinusitis. The diversity in healthcare services and the financial advantages for both employers and employees were significant findings.
Conclusion: The research demonstrates that worksite clinics play a critical role in delivering accessible and cost-effective healthcare to employed adults. They represent a viable model for employer-based healthcare systems, potentially improving the accessibility, efficiency, and cost-effectiveness of healthcare services. Further studies are recommended to explore the broader impacts of worksite clinics on healthcare outcomes and costs
A Comparative Analysis of Costs Associated with Assisted Reproductive Technology; Invitro Fertilization of Singleton, Twin, and Multiple Gestations Compared to Non-Invitro Fertilization Singleton Gestations
Get PDFThis study examines IVF and non-IVF costs associated with prenatal, delivery, and postpartum care using claims data from Merative MarketScan Commercial and Encounter data from 2018-2020 to understand the costs associated with respective IVF singleton, twin, and multiple gestations, as compared to non-IVF singleton gestations. These patients identified as females at birth, were continuously enrolled in private insurance, and have not experienced termination of pregnancy. The Student T-test was performed on continuous variables, and logistic regression was performed on binary variables with the overall outcome variables being cost, IVF, and non-IVF, controlling for age. The cost data was gamma log link transformed to account for the cost variable which is not distributed normally, and multivariable analysis of outpatient visits prenatal and postpartum, hospital stays prenatal and postpartum, length of stay, and total cost of delivery was performed
The Forgotten Occupation in Stroke Rehabilitation: Use of Keyform Mapping to Address Sleep Disturbance & Student Research Therapist Experience
No full textPurpose: The purpose of this MUSC Occupational Therapy (OT) Doctoral Capstone project was to elucidate the concept of post-stroke sleep disturbance by 1) gathering quantitative data from stroke patients using a sleep disturbance questionnaire, 2) conducting qualitative interviews to understand stroke patients\u27 subjective experiences of sleep disturbance, and 3) utilizing Rasch item response theory analysis to develop a person-item map, i.e., a “keyform”, that visualizes the interplay between a patient\u27s sleep disturbance severity-level and specific sleep disturbance symptoms that the patient demonstrates.
Background: Sleep disturbances (SD) affect over 50% of stroke survivors, negatively impacting recovery and increasing risk of mortality (Jeffers et al., 2023; Väyrynen et al., 2014). Although comprehensive management of SD throughout the continuum of care improves outcomes, multifaceted barriers within the stroke rehabilitation system, including resource constraints and fragmented care, limits SD assessment and management. (Hasan et al., 2021; Frange et al., 2023; Brown et al., 2019). There is a pressing need to develop new methods that enable healthcare professionals to more precisely assess and therapeutically manage SD (Fulk et al., 2020).
Methods: This was a secondary analysis of existing data collected from 2 MUSC IRB- approved research projects and all procedures were conducted accordingly. Both studies had similar inclusion criteria: stroke survivors, ≥21 years of age, ≥3 months post-stroke, English as primary language, and able to participate in full study protocols. A trained evaluator administered the PROMIS Short Form v1.0 – Sleep Disturbance 8a questionnaire. Responses were recorded in a secure database (REDCap) and downloaded into Excel for processing. Data were analyzed using both standardized methods (Health Measures Scoring System T-cut off score charts to identify sleep disturbance severity-levels) and Rasch Analysis (Winsteps software). The Rasch analysis output a person-item Keyform map to link individual patient’s assessment scores to specific SD symptoms. In addition, semi-structured interviews were conducted, via HIPAA compliant zoom, with participants who had also completed the PROMIS questionnaire. Interview responses were audio recorded, transcribed, and analyzed using thematic analysis methods.
Results: N=51 participants completed the Sleep Disturbance Questionnaire. N=14 (28%) presented with sleep disturbance in the mild (n=5), moderate (n=6), or severe ranges (n=3). Rasch analysis results showed that individuals with severe SD exhibited higher scores on more severe SD symptoms (i.e. worried about not falling asleep, difficulty falling asleep), while individuals with mild SD exhibited higher scores on less severe SD symptoms (i.e. unrefreshing sleep, restless sleep). Thematic analysis of interviews with n=5 participants revealed a demand for personalized, non-pharmaceutical interventions to alleviate perceived helplessness in managing SD. Participants identified factors impacting their sleep, hindering daily activities, routines, and role fulfillment. SD Item-level perceptions and challenges were further explored to guide interventions.
Conclusion: Together, the Rasch Keyform map and qualitative data elucidated the broad concept of SD in terms of specific symptoms experienced by individuals with mild, moderate, and severe SD. Delineating distinct patient-specific SD issues enables occupational therapists to develop targeted and personalized SD interventions. The results this project reinforce existing literature on the prevalence of SD among stroke survivors while introducing an innovative approach to its assessment and management
Ferroptotic Cardiomyocytes Regulate Angiogenesis in the Regenerative Mouse Heart after Myocardial Infarction through Direct and Indirect Mechanisms
Get PDFCardiovascular diseases (CVDs) are the leading cause of death in the United States, and heart attack occurs every 40 seconds in the US. A myocardial infarction (MI), or heart attack, results in ischemic injury and cardiomyocyte (CM) death. Mature mammalian CM renewal in the heart is insufficient to repopulate the lost tissue. However, the neonatal mouse heart retains its regenerative capacity through the first week of life, providing a valuable model to identifying regenerative factors.
Recent work by our lab revealed that the main mechanism of CM death in the heart post-MI is ferroptosis. In this study, we investigate the effects of ferroptosis by subjecting regenerative postnatal day 1 (P1) and non-regenerative postnatal day 7 (P7) mice to permanent left anterior descending coronary artery occlusion (LAD-O) and treatment with Ferrostatin-1 (Fer-1), a commercially available ferroptosis inhibitor. Echocardiography and histology revealed impaired cardiac function accompanied by an insignificant increase in infarct size. Immunostaining showed decreased endothelial cell (EC) density alongside reduced macrophage infiltration and M2 polarization. Flow cytometry of ventricular tissue confirmed the macrophage phenotype.
To elucidate CM-derived signaling, we differentiated human induced pluripotent stem cells (hiPSCs) into CMs (iCMs). iCMs were exposed to either Erastin or Staurosporine to induce ferroptosis or apoptosis. Human umbilical vein endothelial cells (HUVECs) were treated with conditioned media from treated iCMs for assays characterizing survival, migration, proliferation, and tube formation. HUVECs treated with conditioned media from ferroptotic iCMs exhibited increased survival and angiogenic activity over apoptotic iCM conditioned media treated HUVECs.
Cytokine array analysis allowed characterization of the ferroptotic iCM secretome, leading to the identification of a potential mechanism involving interleukin-19 (IL-19). We utilized computational modeling of publicly available single-cell RNA sequencing data to predict signaling networks between subpopulations of CMs, ECs, and macrophages that included IL-19. Further, IL-19 administration in P7 LAD-O mice lead to improved EC density and proliferation in the infarct, decreased CM ferroptosis, and improved cardiac function.
This project has led to a better understanding of the beneficial effects ferroptotic cardiomyocytes exert on cardiac remodeling after MI, and the role that regulated CM death plays on the wound healing process
A School-Based Occupational Therapy Resource Toolkit
No full textObjective
With a larger percentage of occupational therapy practitioners working in the school-based setting, it is important that entry-level clinicians have access to free resources and information in order to successfully transition into school-based practice.
Methods
A REDcap survey was completed to gather stakeholder needs and determine which resources might be most beneficial to include in a resource toolkit for new clinicians transitioning to school-based practice. REDcap participants included 155 individuals (N=155) from 36 different states in the United States included in the REDcap survey sample. Of the 155 participants, 115 (73.3%) are occupational therapists, and 39 (25%) are certified occupational therapy assistants. Participants reported concerns include meetings (48.1%), scheduling (48.1%), high caseloads (45.5%), lack of mentorship and teams (41.7%), engagement with school staff (32.7%), understanding laws, policies, and regulations (29.5), itinerant schedules (16%), and treatment sessions (9.6%). Based on these results, a toolkit was created and housed electronically to provide free, accessible, and comprehensive resources for the new school based occupational therapy professionals. Following the creation of the toolkit, participants received access to the resource. Surveys were distributed to evaluate the usability, perceived helpfulness, and perceived quality of the toolkit.
Results
Following the utilization of the toolkit, 25 (N=25) participants completed a survey analyzing the quality, helpfulness, and usability of the completed toolkit. Participants were to rate these areas on a scale of 1-10. The results from the feedback survey demonstrate perceived means of 8.32/10 for quality, 8.52/10 for helpfulness, and 8.64/10 for overall usability. Participants report that they would be likely to recommend the toolkit to a colleague and they feel it meets expectations. There were areas the participants felt could be expanded upon or added to improve the toolkit, which could lead to opportunities for continued growth of the project. Figures F-H in the appendices provide more information on the data results.
Conclusion
This resource toolkit will provide information and education to practitioners so they may adequately serve their clients and work within the unique nature of school system
Opportunistic Pathogen Porphyromonas gingivalis Targets the LC3B-ceramide Complex and Mediates Lethal Mitophagy Resistance in Oral Squamous Cell Carcinoma
No full textAdvancements in cancer therapies and early detection have allowed mortality rates for many cancers to drop or remain consistent over the past 30 years. Contrary to broad improvements in the treatment and incidence of head and neck cancers overall, oral squamous cell carcinoma (OSCC), particularly of the base of the tongue, has been increasing in prevalence. Considering the low five-year survival rate and high recurrence and metastasis of this cancer type, identification of novel patient subgroups and unknown risk factors is needed. Porphyromonas gingivalis (P. gingivalis) is a gram-negative, asaccharolytic anaerobe that resides in the oral cavity. P. gingivalis is notable as the keystone pathogen for adult periodontitis, and for its ability to invade human primary gingival epithelial and endothelial cells to evade immune clearance and successfully replicate within host cells, persisting as a chronic infection. Notably, P. gingivalis has been reported to occur at a higher concentration in OSCC tissue compared to adjacent normal gingiva. The severity of OSCC mortality was also correlated with serum antibody levels to P. gingivalis and periodontal disease progression. These reports indicate that P. gingivalis may be an additional risk factor influencing the severity and development of OSCC in patients. OSCC have been shown to downregulate ceramide synthase 1, which produces the signaling sphingolipid, C18-ceramide. C18-ceramide is key in initiating LC3B-mediated lethal mitophagy and tumor suppression, often induced by chemotherapeutic and radiotherapeutic cancer treatment. Treatment of OSCC cells and orthotopic tumors with a C18-ceramide analogue drug to potently induce mitophagic stress has revealed that P. gingivalis infected cells exhibit inhibited lethal mitophagy. It was found that P. gingivalis disrupts the LC3B-ceramide complex to repress lethal mitophagy induced by various drugs by utilizing major fimbriae A (FimA). This is accomplished through novel binding of FimA to ANXA2, which prevents ANXA2-ceramide association involving E142 residue of ANXA2. By disrupting ANXA2 association with ceramide, the ANXA2-ceramide-LC3B complex that induces lethal mitophagy is also inhibited by P. gingivalis. A FimA-deleted mutant variant of P. gingivalis was unable to repress ceramide-dependent mitophagy. In addition, 16S rRNA sequencing of orthotopic OSCC tumors revealed that P. gingivalis induced changes to the tumor microbiome in response to LCL768 treatment, elevating the abundance of Gordonia, Stenotrophomonas, and Herbaspirillum. This study reveals that P. gingivalis assists OSCC survival through inhibition of ceramide-dependent lethal mitophagy. New targets for possible therapeutic targeting, such as FimA, have been identified to improve treatment response in OSCC tumors infected with P. gingivalis
A Mechano-Molecular Landscape Underlying Regionalized Left Ventricular Fibrosis in Mitral Valve Prolapse
No full textMitral Valve Prolapse (MVP) is a common heart valve condition characterized by superior displacement of one or both mitral valve leaflets during systole and often failure of leaflet coaptation. Although historically thought of as a benign condition, with secondary consequences thought to occur as a result of worsening mitral regurgitation (MR), recent studies have highlighted an association between MVP, regionalized myocardial fibrosis of the subvalvular myocardium, and potentially lethal ventricular tachyarrhythmias including ventricular tachycardia (VT) and ventricular fibrillation (VF). Often, patients who present with life-threatening arrhythmias have a phenotypically “moderate” regurgitation and are not surgical candidates; Yet, other clinically measurable variables suggest these patients present with a mechanically severe form of MVP, characterized by bi-leaflet involvement, abnormal myocardial and annular mechanics during systole, and mitral annular disjunction (MAD). Nonetheless, current AHA/ACC medical and surgical guidelines do not adequately risk stratify MVP patients based on the mechanical severity of their disease. Furthermore, the underlying mechano-molecular interactions that initiate and sustain fibrosis and arrhythmias in MVP are not well understood and represent an unmet clinical need for therapeutics which can slow or reverse mechanically-induced fibrosis. This dissertation reviews the macroscopic and microscopic anatomy of the mitral valve as well as what is known about the clinical causes and consequences of mitral valve prolapse, including ventricular arrhythmias. We further test the hypothesis that mitral valve prolapse induces regionalized left ventricular fibrosis by increasing mechanical stress on the subvalvular myocardium, which in turn activates fibrogenic pathways within cardiac fibroblasts. In aim 1, we demonstrate regionalized myocardial fibrosis occurs in human patients at the time of MV surgery with increases in CD206 expressing macrophages, and a-Smooth Muscle Actin expressing myofibroblasts in valve-linked myocardial regions. We additionally show that induction of MVP using a geneticallyaccurate mouse model of human non-syndromic MVP phenocopies the human findings and causes progressive myocardial fibrosis with time. In aim 2, we develop a non-genetic surgical model of MVP in a large animal which allows us to induce prolapse and the associated mechanical stress with a genetically normal myocardium and test the response of subvalvular myocardium to mechanical stress. We show that surgical induction of MVP causes regionalized fibrosis, consistent with a mechanism of regionalized fibrosis secondary to abnormal valve induced mechanical stress on the subvalvular myocardium. In aim 3, we apply mechanical stress in the form of stiffness to primary human cardiac fibroblasts and perform an integrative, multi- ‘omic’ profiling analysis in order to identify pathways which drive mechanical stress-induced fibrosis. We show that mechanical stress induces broad transcriptional and epigenetic changes consistent with upregulation of fibrogenic pathways. Our results identify the mechanosensitive gene MYH10, which encodes non-muscle myosin IIB, and demonstrate how transcription of MYH10 is epigenetically regulated by mechanical stress through an intronic repressor element which binds the transcription factor JUND. Finally, we highlight potential upstream signaling pathways which may regulate MYH10, including purinergic signaling by Connexin 43 hemichannels. Conclusions from this work are that regionalized fibrosis in MVP is progressive, occurs secondary to the valve defect, and is in part driven by pathways which may be targeted using pharmacotherapeutics. Our work further questions whether earlier surgical intervention in a subset of MVP patients may reduce the risk of lethal ventricular arrhythmias and be of therapeutic value
An N-glycan Tissue Atlas of Multiple Tissue Types and a Focus on DCIS
No full textN-glycosylation is an abundant post-translational modification of most cell-surface proteins and is critical to many cellular functions. Each organ has its own distinct N-glycome which often becomes altered in disease states, especially cancer, and serve as some of the best clinical biomarkers. However, N-glycan atlasing is far from complete, both in general tissues and specific diseases, such as ductal carcinoma in situ (DCIS). DCIS is a pre-invasive, highly prevalent breast cancer with very low chances of progressing to invasive ductal carcinoma (IDC) yet is treated aggressively with no current method to predict progression. To address these issues, I used N-glycan-targeted MALDI mass spectrometry imaging for two specific aims: 1) generating a reference database of N-glycans for matched normal and tumor tissue types and 2) identifying the N-glycome of DCIS and determining differences between pure DCIS and DCIS that has progressed into IDC as well as between primary DCIS lesions with known outcomes. In Aim 1, N-glycomes of fifteen tissue types and their respective cancers were profiled. It was found that oligomannose N-glycans and core fucosylated multiantennary N-glycans were more abundant in most cancers, and exceptions to these patterns were identified. Individual N-glycans of various kinds were significantly altered in cancer for each tissue type. Overall patterns demonstrated reduction of tissue-specific N-glycosylation patterns in corresponding cancers. Sialylation and core fucosylation were also profiled in depth. For Aim 2, the profiling methods of Aim 1 were applied to DCIS to examine differences between un-progressed and progressed DCIS as well as primary lesions with known outcomes. N-glycans colocalizing to DCIS were identified and oligomannose structures were prominent among these. Several N-glycans were determined to be significant between pure DCIS and DCIS in IDC and between DCIS that did and did not eventually progress into IDC. Gene expression of N-glycosylation-related genes was also analyzed, indicating increased branching and decreased glycoprotein quality control in DCIS that would later progress. These findings offer valuable wide-scale information for normal and cancerous tissues and DCIS, indicating potential biomarker candidates for DCIS progression and serving as a reference for future studies and potential diagnostic applications of MALDI-MSI
Home Health Utilization and Health Outcomes for Medicare Fee for Service Survivors of Acute Ischemic Stroke
No full textNot all survivors of acute ischemic stroke (AIS) discharged home after hospitalization with a HH referral receive HH and some survivors discharged home to self-care receive HH. Broad population level HH utilization pattern studies are needed to assure optimal access to HH.
Three retrospective observational cohort studies describe HH referral patterns, use, and cost, comparing those discharged home to self-care vs. discharged home with a HH referral. Thirty day hospital readmission rate, demographics, and diagnoses for a subset of 251 survivors are described.
Survivors who were older, female, Medicaid eligible, or had a greater comorbidity burden were more likely to receive a HH referral. A subset with HH and a HH referral received HH sooner, had a more complex inpatient stay, and a more severe stroke than those discharged home to self-care. Those with severe strokes referred home to self-care had 5 more HH visits. Hospital readmission rate was 21.9%, averaging $14,046. Approximately half were readmitted prior to receiving HH, 73.3% for recurrent stroke or stroke-related complications.
These results show a need to examine referral practices to identify opportunities to improve fit between HH referral and HH use and support future study of hospital discharge and community follow up processes