MEDICA@MUSC (Medical University of South Carolina)
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Factors Associated with Loss to Follow-Up in a Cohort of Proliferative Diabetic Retinopathy Patients Who Have Received At least One Anti- Endothelia Growth Factor Injection Therapy
No full textObjective: The aim of this study is to identify factors associated with loss to follow-up (LTFU) in patients receiving treatment for proliferative diabetic retinopathy (PDR). The current study seeks to characterize the proportion of patients with PDR who were LTFU in clinical practice and to evaluate potential factors related to LTFU. Methods: A Retrospective study utilizing a 5% sample of Medicare claims data between 2017-2019 was conducted to determine risk factors associated with LTFU in PDR patients who have received at least one anti-endothelia growth factor injection (VEGF). Descriptive statistics was performed to compare PDR patients who are and are not LTFU. Mean and standard deviations were used to describe continuous independent variables and counts, and percentages were reported for categorical data. Generalized linear models with poisson distribution and log Link were performed to estimate the relative risk of being LTFU. Results: The study found that both 6-Month (84.0%) and 12-Month LTFU (73.0%) rates were exceedingly high for patients who have received at least one VEGF for PDR from 2017-2019. A total of 551 patients in whom PDR was diagnosed met the criteria. When examining the factors associated with 6-month and 12-month LTFU, age, sex, and race were not statistically significantly predictive. However, with every 100 days those patients remain in treatment, the relative risk decreased by 7% (6-month LTFU) and 8% (12-month LTFU). Among patients who died during follow up, their relative risk decreased by 42.8% (6-month LTFU) and 67.7% (12-month LTFU) than those who did not die (p-value \u3c 0.0001). The relative risk increased both at 6-month LTFU (20.8%) and 12-month LTFU (35.9%) for those who had more than 5 treatment injections. We also saw the relative risk increased by 11.8% in those who had dual eligibility during 12-Month LTFU but was not statistically significant in patients that were 6-months LTFU. Conclusion: This study highlights some new insights into this cohort, but additional questions remain, and future studies should be performed to investigate reasons for LTFU in this patient population related to comorbid disease, severity of vision loss, and psychological factors potentially related to LTFU for which this study was unable to address
Waring Library Society Newsletter, Spring 2022
Get PDFThis issue includes a welcome message from incoming WLS President, Dr. Jacob Steere-Williams and an outgoing message from Dr. James H. Tolley as WLS President (2020-2022). Also, in this issue, Dr. Brian Fors provides an update on the renovation plans for the Waring; Ms. Judith Arendall describes a typical day at the Waring in her experience as a graduate assistant; Ms. Tabitha Samuel reflects on her experience this year as one of South Carolina\u27s regional coordinators of the SC History Day Contests; Ms. Anna Schuldt highlights the Waring\u27s social media commemoration of MUSC history makers for Black and Women\u27s History Months; Ms. Brooke Fox announces We Are All Affected: 40 Years of HIV/AIDS in SC Symposium, hosted by the Waring; and Dr. Fors Highlights materials from the Waring\u27s collection relating to women\u27s health.https://medica-musc.researchcommons.org/wls-newsletters/1003/thumbnail.jp
Creation of Faculty Resources for Educational Technologies via Manual Muscle Testing Curricular App into Innovative Learning Environments
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Beyond Traditional Practice: The Role of OT in Community Development Lowcountry Food Bank & University of Cape Town, OT Division
Get PDFAdvanced Diffusion MRI Development with Application to Neonatal Brain Injury
Get PDFCompared to histology, few methods can provide such elegant insight into brain tissue microstructure. While still considered the gold standard for microstructural validation, as it has micron-level resolution, it is time-consuming and typically performed postmortem which limits its practicality. Non-invasive diffusion MRI (dMRI) is sensitive to the diffusion of water which is typically within the micrometer length scale. Clinically, dMRI is used widely to visualize ischemic lesions after stroke in a qualitative sense. As many structures in the brain tissue milieu are on this micron-level order of magnitude, such as axons that have diameters ~1–10 microns, dMRI is well-situated to probe tissue microstructure. Even still, the biophysical interpretation of the dMRI signal in healthy, let alone injured, tissue is complex, and validation is still ongoing. In clinical research, there are many dMRI applications, but for this dissertation we studied neonatal brain development after either preterm or hypoxic-ischemic (HI) birth using dMRI. Typically, the eventual motor and cognitive deficits that arise due to these insults do not show up until later in development, around 12 months. Our objective was to determine if dMRI, specifically diffusional kurtosis imaging (DKI), acquired early in development, near day of life 5–7, could predict long-term outcome scores as measured by standardized developmental testing at 12–18 months of age. Additionally, we also sought to determine the effect, if any, that novel treatment regiments for both preterm infants receiving novel non-invasive brain stimulation paired with bottle feeding and term aged HI infants getting N-acetylcysteine would have on the quantitative diffusion metrics we can derive from DKI, namely the diffusivity and kurtosis. Lastly, we wanted to see if any of the derived DKI metrics could help identify responders to the novel stimulation therapy or provide indicate HI severity. If shown to be helpful, advanced quantitative dMRI would help elicit inform the initiation of earlier and more targeted habilitation therapies for this critical population of neonates. As we will show in this dissertation, there was marked improvement into long-term outcome model predictions using kurtosis metrics. Moreover, it was found that the mean kurtosis was able to delineate those who would respond or not to the novel stimulation therapy in preterm feeding. It was also found that both the fractional anisotropy and radial kurtosis increased more from pre- to post-treatment in responders than in non-responders. This would indicate a greater degree of restriction and directionality to the water movement and thus greater cellular integrity of axons and/or cellular barriers. Lastly, we found that there exist differences in the kurtosis based on the timing for the scan in acute (decreased kurtosis) or convalescing (increased kurtosis) HI. Interestingly, we also found that the kurtosis fractional anisotropy, given the degree of anisotropy of the kurtosis tensor only, provided support in modeling HIE severity and outcomes. DKI has not widely been studied in neonatal development, with only a handful of studies published. This work represents another building block to fully characterize this method which improves upon the current clinical standard diffusion tensor imaging (DTI) in identifying treatment response and, insult severity stage, and helping predict long-term outcomes. This dissertation also focused on the development of more advanced dMRI methods than are typically employed or ready for translation to the clinical setting. The main technique we developed and characterize in depth throughout this body of work is fiber ball imaging (FBI). One of main features of FBI compared to DKI is the use of large diffusion weightings or b-values. DKI typically uses b-values of 1000 and 2000 s/mm2 whereas FBI requires at least 4000 s/mm2 and many sampling directions. The large diffusion weighting isolates the intra-axonal water by acting as a filter for extra-axonal water that is a confounding element at the lower b-values of DKI. With FBI, we can estimate what is known as the fiber orientation density function (fODF) which is related to the angular spread of axon fiber bundles. Using the fODF, and its associated elements, we can calculate the fractional anisotropy of axons (FAA) and the Matusita anisotropy (MAA) that provide insight into the intra-axonal white matter (WM) space specifically. Furthermore, we developed a method to quickly and easily rectify negative values that arise during the fODF estimation. We also show that this method can be used for any fODF estimation technique as well. Using a novel diffusion protocol, triple diffusion encoding (TDE), we provide a means to get a more reliable value for the intrinsic intra-axonal diffusivity, which can slightly improve the fODF estimation. TDE is simple to implement and has only a few modeling assumptions, but as it involves no numerical fitting it can serve as a basis for comparison and validation of various single diffusion encoding white matter models whose data is easier to acquire but require more modeling assumptions. Lastly, we have devised a way to use the fODF as the basis for comparisons rather than its typical use as an input for other models or white matter fiber tractography. We call this high-fidelity FBI. Briefly, we rotate each fODF (there is one for each white matter imaging voxel) into a local coordinate frame such that they are now able to be compared within and across subjects. This is done using the Matusita distance which gives a single value relating to the similarity or difference of the fODFs being compared. As the fODF is a physical entity, we believe that subtle changes in the fine structure of the fODF, say across age, will provide a new dMRI contrast to observe changes in white matter pathology or aging and dementia, such as Alzheimer’s disease. In total, this thesis work has so far led to 5 peer-reviewed papers, with 2 more planned, and several abstracts at international conferences
Waring Library Society Newsletter, Fall 2022
Get PDFIn this issue, WLS President Dr. Jacob Steere-Williams reflects on the changing seasons in Charleston and its impact on public health, and the Waring’s Curator Dr. Brian Fors discusses the events leading up to the founding of the Medical College of South Carolina. This issue also features an introduction to the Waring’s newest team member, Dr. Gabriella Angeloni, the Waring’s Historian, while Ms. Brooke Fox highlights an unexpectedly dangerous find in the Pharmacy Museum and Ms. Tabitha Samuel announces the launch of the new Waring Historical Library Digital Collections website and [email protected]://medica-musc.researchcommons.org/wls-newsletters/1001/thumbnail.jp
Armed Conflicts, HIV Testing, HIV Prevalence, and High-Risk Sexual Behaviors: An Epidemiologic Analysis
Get PDFArmed conflicts have a wide array of consequences on health and behavior possibly serving a role in the spread of HIV, yet there is limited research on the quantitative association between armed conflicts and HIV. To address this gap in the literature, we evaluated the effect of armed conflicts on HIV testing, HIV prevalence, and high-risk sexual behaviors, using Demographic and Health Surveys data from 11 countries in Sub-Saharan Africa (years 2010 to 2018) and the Armed Conflict Location & Event Data. We hypothesized that armed conflicts, measured using number of conflict days, fatalities, or distance to nearest conflict, would be associated with reduced likelihoods of HIV testing, higher likelihoods of HIV prevalence, and higher occurrences of high-risk sexual behaviors. We developed three specific aims to 1) compare HIV testing, HIV prevalence, HIV knowledge and attitudes, and high-risk sexual behaviors between conflict and non-conflict areas, 2) determine the association between armed conflicts, HIV testing, and HIV prevalence and 3) determine the association between armed conflicts and high-risk sexual behaviors. We utilized a cross-sectional ecologic study, descriptive statistics such as maps, plots and two-sample T tests for the first aim and generalized linear mixed effects models with spatial random effects while adjusting for common confounders for subsequent aims. For these analyses, we used data from 168 administrative regions. Of these, 79 experienced conflict with an average of 87 days spent in conflict and 200 fatalities. In Aim 1, we found significantly lower HIV prevalence, stigma, previous HIV testing, and HIV knowledge in conflict areas. In Aim 2, armed conflicts were significantly associated with lower rates of HIV prevalence but not with previous HIV testing. In Aim 3, number of days and fatalities were significantly associated with increased rates of high-risk sexual behaviors but close proximity to an area of conflict was significantly associated with lower rates of high-risk sexual behaviors. Our findings illustrate that the relationship between armed conflicts and HIV measures is complex and is influenced by conflict duration, intensity, and proximity. Future studies should consider accounting for temporality and utilizing different populations exposed to higher intensity conflicts
Telehealth Utilization in Response to the COVID-19 Pandemic: Current State of Medical Provider Training
Get PDFBackground: The COVID-19 pandemic accelerated the development of telehealth services and thus the need for telehealth education and training to support rapid implementation at scale. A national survey evaluating the current state of the telehealth landscape was deployed to organizational representatives, and included questions related to education and training. Materials and Methods: In the summer of 2020, 71 survey participants (31.8%) completed an online survey seeking to determine the utilization of telehealth services across institutional types and locations. This included data collected to specifically compare the rates and types of formal telehealth education provided before and during the pandemic. Results: Thirty percent of organizations reported no telehealth training before COVID-19, with those in suburban/rural settings significantly less likely to provide any training (55% vs. 82%) compared with urban. Pandemic-related training changes applied to 78% of organizations, with more change happening to those without any training before COVID-19 (95%). Generally, organizations offering training before the pandemic reported deploying COVID-19-related telehealth services, while a higher percentage of those without any training beforehand reported that they either did not plan on providing these services or were in the early planning stages. Discussion: Telehealth education is moving from elective to essential based on the need to prepare and certify the workforce to support high-quality telehealth services. Conclusions: As telehealth continues to evolve to meet the future health care service needs of patients and providers, education and training will advance to meet the needs of everyday clinical encounters and broader public health initiatives
VDAC and Mitochondrial Bioenergetics in Cancer Biology and Therapeutics
Get PDFThe contribution of mitochondria to cancer cell metabolism is a continuously growing research field. Enhanced glycolysis and partial suppression of mitochondrial metabolism, reciprocally dependent in many tumors, characterize the pro-survival and proliferative Warburg phenotype. Voltage dependent anion channels (VDAC), in the outer mitochondrial membrane (OMM), regulate the flux of most respiratory substrates entering and exiting mitochondria. Thus, VDAC functions as a switch to turn-on (when open), and off (when closed), mitochondrial metabolism. Previous work from our lab showed that VDAC modulates mitochondrial metabolism in cancer cells, high cytosolic free tubulin closes VDAC, and the synthetic VDAC-binding molecule erastin, antagonize the inhibitory effect of tubulin on the channel. Here, it is demonstrated that mitochondrial dysfunction leading to cell death after the VDAC openers erastin/erastin-like compounds, or the chemotherapeutic agent sorafenib, is induced by a ROS-dependent translocation of activated JNK to mitochondria. Mitochondrial membrane potential (ΔΨm) was used as a global readout of mitochondrial function and observed heterogeneity of ΔΨm, a phenomenon previously described only qualitatively. Using an advanced confocal microscopy approach, ΔΨm was quantified among cells in absolute values and proved that ΔΨm heterogeneity is an intrinsic property of mitochondria. In addition, this quantitative approach to assess ΔΨm by imaging, we developed a novel, sensitive and fast method to assess ΔΨm, NADH generation and electron flow in permeabilized and intact cells using a combination of plate reader and respirometry assays was developed. This method provides fast-tracked medium throughput outcomes in phenotypic assays of mitochondria. Finally, VDAC was used as a pharmacological target to identify in silico small molecules that bind to the NADH-binding pocket of VDAC. NADH binding to the pocket closes the channel so occupying this region with another molecule would prevent VDAC closure by endogenous regulators, maintaining the channel in an open configuration. A lead compound was identified that binds to VDAC, induce mitochondrial dysfunction, and promote cell death. Overall, the work described here contributes to a better understanding of cancer metabolism, provides novel methods to study mitochondrial metabolism, and initiates a potentially highly relevant translational application of VDAC modulation into cancer treatment