MEDICA@MUSC (Medical University of South Carolina)
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Characterization of CD45+ Primary Fibroblasts in Interstitial Lung Disease
Get PDFThe role of cells of the hematopoietic lineage in fibrosis associated with interstitial lung disease (ILD) is controversial; whether monocytes solely differentiate into macrophages that activate resident fibroblasts, or if they can also differentiate into fibrocytes (CD45+/Col I+ cells) that then differentiate into fibroblasts has been debated. By using systemic bleomycin to induce fibrosis in a bone marrow transplant and transgenic mouse models, as well as using human lung tissue from a patient with scleroderma-associated ILD, we studied the contribution of the hematopoietic lineage to the fibroblast population using flow cytometry and single cell RNA sequencing. Further, our studies revealed reasons why fibrocytes are lost when fibroblast cultures are passaged. Finally, we evaluated how treatment of mice with a novel, water-soluble version of caveolin scaffolding domain (CSD) called WCSD affects fibrocyte accumulation and fibrosis in our animal model. We found that during fibrosis, fibrocytes increase in number and in their expression of Col I both in the lung tissue and in the bronchiolar lavage fluid (BAL). The appearance of Col I in CD45+ precursors occurs after their recruitment into the lung. Interestingly, fibrocytes express higher levels of monocyte/macrophage markers (CD45, CD16, CD68, CD206) than do CD45+/Col I- cells. In vitro experiments demonstrated that CD45+/Col I+ cells are at first predominant in fibroblast cultures, but then are lost progressively during passage. Furthermore, these fibrocytes do not appear to grow in vitro in the absence of CD45-/Col I+ fibroblasts. Treating mice with WCSD inhibited fibrocyte accumulation as well as overall collagen I, Tenascin C, α-sma, and HSP47 levels and vascular leakage. The decreased fibrocyte accumulation may result both from decreased precursor recruitment due at least in part to decreased vascular permeability and from decreased differentiation of fibrocytes from CD45+/Col I- precursor monocytes. In summary, CD45+ cells accumulate in lung tissue during fibrosis and contribute to pathological remodeling by differentiating into myofibroblasts that overexpress ECM proteins and myofibroblast markers. Their contribution to fibrosis can be inhibited by WCSD which serves as a surrogate for caveolin-1, a protein known to be reduced in expression in multiple cell types from patients with fibrotic lung disease
Transcutaneous Auricular Vagus Nerve Stimulation (TAVNS): Long-Term Effect on Neurodevelopment and Sensory Performance
Get PDFInfants who do not succeed at early feeding are likely discharged from the nursery with a gastrostomy tube (G-tube), putting them at risk for worse neurodevelopmental and sensory outcomes than infants who achieve full oral feeds. This study aims to investigate the impact of Non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) on infants\u27 early motor development and long-term neurodevelopmental sensory performance at 18 months. Besides the observed feeding improvement using taVNS paired with bottle-feeding, we explore if pre-treatment total STEP scores\u27 is able to predict response to taVNS intervention. The pre-treatment total STEP scores did not contribute to the prediction model significantly. Then, we looked at the long-term effect of early taVNS treatment in both neurodevelopmental and sensory outcomes at 18 months follow-up. We found that infants who responded to early taVNS treatment when paired with bottle-feeding had better overall neurodevelopmental outcomes than non- responders. We also found that responders had significantly better typical scores in the general sensory section, and had more typical average mean scores in almost all the sensory profile sections than non-responders. These preliminary results are encouraging of the use of taVNS. Future studies can include randomization of active and control taVNS intervention with larger sample size
Missing Pieces in Health Services Cost Analysis: Consensus on Modeling, Magnitude, and Micro-Costing
Get PDFCost and cost savings have become an important focus for health policy administrators. However, there are missing pieces in our approach to cost analysis; there is no consensus on multivariable methods, no indicators of minimally acceptable values, and no specification of process costing. In this dissertation, I propose to fill the gaps in the literature by 1) identifying which methods are appropriate for large claims data, 2) examine existing methods to establish minimally important difference (MID) in health outcomes to identify MID in costs, and 3) determine differences in sick visit clinic costs using a modified micro-costing method. Most models that were compared to the generalized linear models Gamma distribution with log link found it to be the superior model in both simulated data and real administrative data. We recommend that in cases where acceptable anchors are not available to establish an MID, both the Delphi and the distribution-method of MID for costs be explored for convergence. Our micro-costing approach is feasible to use under virtual working conditions; requires minimal provider time; and generates detailed cost estimates that have “face validity” with providers and are relevant for economic evaluation
Legality and Considerations for Healthcare Chief Information Officers Migrating to the Public Cloud
Get PDFThere are many advantages for healthcare organizations to use the public cloud for storage/computing. However, moving data outside of the organization’s physical boundaries implies lost or reduced control and greater reliance on Cloud Service Providers (CSP) in determining where the data is stored and how it is secured. When that data is sensitive healthcare data and at high-risk for cyber/national security violations as well as, belonging to U.S. citizens, the need for careful planning and legal compliance increases sharply. The following study evaluates the legality and considerations of public cloud use for healthcare Chief Information Officers (CIO) and the need for holistic federal regulation in order to protect healthcare data from foreign and domestic threats. Healthcare CIO’s cannot continue to wait to move into the next century of technologies due to the current lack of legislative protection, which is hindering their ability to act swiftly and confidently in front of their board members, executives, peers, employees, and patients. In this study, we prove a need for the US legislative system to provide a unified legal framework that protects and enables healthcare organization to migrate their workloads/data to the public cloud using CSP’s without fear of retaliation through the US legal system
The Symptom Experience of Black Women with Heart Failure Preserved Ejection Fraction
Get PDFBackground: Heart failure (HF) is a prevalent disease with a complex symptom experience. Black women with Heart Failure preserved Ejection Fraction (HFpEF) are especially burdened by symptoms, and their symptom experience is poorly understood. Clustering HF symptoms to understand which symptoms are experienced together is a potential option for helping patients recognize impending exacerbations. Methods: The dissertation\u27s first manuscript is an integrative review to examine the current state of HF symptom cluster literature. The second manuscript explores the feasibility and acceptability of a mixed methods HF symptom cluster study of Black women with HFpEF (N=44) and presents preliminary symptom cluster results. The third manuscript presents symptom experience themes from qualitative interviews (N=15) and integrates those findings with quantitative questionnaire data. Findings: An integrative review of HF symptom cluster literature revealed a need for exploring the symptom experience of Black women with HFpEF using mixed methods. A convergent-parallel mixed methods study protocol met feasibility benchmarks and was deemed acceptable by Black women with HFpEF. Preliminary symptom clusters were identified using quantitative symptom data from symptom questionnaires. Qualitative themes emerged relating to the symptom experience and person, and mixed methods integration provided additional key findings of concordance, discordance, and expansion. Conclusion: This dissertation describes the symptom experience of Black women with HFpEF, provides valuable information on the recruitment of an understudied population and their acceptability of a study protocol, and builds the foundation for conducting a mixed methods HF symptom cluster study with a larger sample in the future
Validity of Three Cephalometric Analyses for Diagnosis of the Anteroposterior Postion of the Maxilla
Get PDFPurpose: The purpose of this investigation was to investigate the validity of 3 different cephalometric analyses used for diagnosis of the anteroposterior (AP) position of the maxilla. Methods: Retrospective data including a pre-treatment cephalometric radiograph, repose and smiling profile photographs, and a clinically determined upper incisor to Glabella Vertical (GV) measurement were collected from 30 consecutive patients. Photographs were deidentified with eye coverage and presented in survey form to groups of orthodontists and oral surgeons who judged the maxillae as prognathic, orthognathic, or retrognathic. Corresponding cephalometric radiographs were evaluated using McNamara, Steiner, and GV analyses. Cephalometric diagnoses and clinical impressions were compared to determine which analysis correlated best with clinical impressions. Results: There was a difference between clinical impressions of the AP position of the maxilla in smiling and repose profiles. There was a difference in diagnosis of AP position of the maxilla using the Steiner, McNamara and GV analyses. There was a correlation between clinical impression of repose profiles and diagnosis with the Steiner analysis. There was a correlation between clinical impression of smiling profiles and diagnosis with the GV analysis. Conclusions: Both repose and smiling profiles should be evaluated for comprehensive orthodontic treatment planning. The Steiner and GV analyses are useful tools for diagnosing the AP position of the maxilla on a cephalometric radiograph. Cephalometric analysis using GV may be a more valid analysis due to its superior correlation with clinical impressions of smiling profiles
Emergency Triage, Treat, and Transportation Model (ET3) if Successfully Implemented in North Carolina: A Simulation Based on 2017 Medicare Billing Data
Get PDFEmergency department (ED) visits are increasing and a growing number of non-emergency patients are using EMS for non-urgent transportation to EDs. The costs of ED visits far exceed the costs of physician office visits and a significant number of patients are transported to EDs by EMS for low-acuity visits that have the potential to be seen in lower cost care settings. The objective of this study was to calculate potential cost savings from diverting EMS transports from traditional ED destinations to physician offices due to implementation of the ET3 Model. The (2017) Medicare 5% Limited Data Set and 2017 NC HCUP State Emergency Department Database were used to extract all records for Medicare beneficiaries, Medicaid beneficiaries, private payers, and other payers in North Carolina. All medical transportation bills associated with ambulance transport and low-acuity ED visits resulting in a discharge to home outcome were analyzed for cost savings related to ED charges and traditional office charges. With full implementation of ET3 in North Carolina, the potential annual Medicare savings is 5,330,024, (Medicaid), 8,350,396 (other payers). This represents a cumulative cost savings of $69,832,524
Methods for Modeling Differential Site Initiation Within the Subject Accrual Process with Applications to the Design and Conduct of Multisite Time-to-Event Clinical Trials
No full textFor multisite time-to-event clinical trials, the site initiation and resulting subject accrual process are important but often difficult parameters to predict in the design phase. Multiple factors influence the accrual of subjects into a trial including number of sites, recruitment rate of each site, and the site initiation pattern. An improvement in prediction of the overall subject accrual may positively impact many aspects of the design and conduct for this type of trial, such as sample size calculation, logistics planning, and interim analyses. While many improvements have been made for predicting subject accrual, methodology that accounts for a non-uniform site start-up process that includes a lag in site initiation has not yet been developed. Being able to account for this lag at the beginning of the start-up period will allow for a better prediction of when subjects can be enrolled in the study. These updates are particularly useful in maximum duration time-to-event clinical trials, which assume that subjects are followed from enrollment to end of study with a minimum follow-up specified. Under a maximum duration design, the maximum information is influenced by subject follow-up time as the trial is designed to continue until a specified time. Neglecting differential site initiation can lead to an underestimate in variability of subject accrual, which impacts the predicted subject follow-up time and number of events observed. Thus, this dissertation uses the Program Evaluation and Review Technique (PERT) distribution to account for differential site initiation. The first aim uses the PERT distribution as a model for site initiation to update both the sample size formula and the Poisson-Gamma accrual model for logistics planning. Similarly, the second aim uses the PERT distribution as a model for site initiation to update the information fraction used to determine statistical significance within a group sequential design. The third aim uses the PERT-adjusted sample size formula, PERT-adjusted subject accrual models, and PERT-adjusted information fractions from the first and second aims in a sample size re-estimation. Overall, the developed methodologies allow for additional flexibility to account for the previously underestimated variability in subject accrual during the site initiation period
Building Telehealth Teams of the Future Through Interprofessional Curriculum Development: A Five-Year Mixed Methodology Study
Get PDFBuilding the next generation of telehealth enabled professionals requires a mixture of team-based, interprofessional practice with novel technologies that connect providers and patients. Effective telehealth education is critical for the development of multidisciplinary training curricula to ensure workforce preparedness. In this study, we evaluated the impact of a formal telehealth education curriculum for interprofessional students through an online elective. Over 12 semesters, 170 students self-selected to enroll in the 3-credit hour interprofessional elective and took part in structured didactic, experiential and interprofessional learning opportunities. Mixed-method assessments show significant knowledge and confidence gains with students reflecting on their roles as future healthcare providers. The results from five years’ worth of course data shows not only an opportunity to advance the individual knowledge of trainees, but a larger movement to facilitate changes in practice toward population health goals. Recent global health events have further highlighted the need for a rapid response to public health emergencies by highly trained provider teams who are able to utilize technology as the cornerstone for the continuity of care