MEDICA@MUSC (Medical University of South Carolina)
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Hospital-Based Buprenorphine-Focused Interventions for the Treatment of Opioid Use Disorder: A Scoping Literature Review and Case Study
Get PDFThe United States continues to struggle to find meaningful solutions to the opioid epidemic. Because they save lives, medications for the treatment of opioid use disorder (OUD), such as buprenorphine, are recommended to be made available in all practice settings. Yet the treatment of opioid use disorder appears to be rarely offered during hospitalization. However, a 220-bed academic hospital in Texas achieved this goal without the presence of an addiction medicine consultation service. This study sought to illuminate this growing area of work through an extensive literature review and case study of the program in Texas. For the case study, key informant interviews took place of stakeholders engaged in the program in addition to document review from the program’s inception. Over 4,500 computer files and over 9,400 emails were reviewed from November 2017 to December 2019. Eleven key informant interviews were conducted. The findings show key areas for integration of OUD treatment within the walls of U.S. hospitals including stakeholder engagement, executive support, interprofessional collaboration, widespread education, stigma reduction, advocacy and institutional policy reform, and sharing of patient stories. As a result, a dedicated group of interprofessional hospital-based healthcare professionals working in a consultative model is one feasible method of increasing access to life-saving treatment and harm reduction for patients with opioid use disorder and likely substance use disorders as a whole
Trends in Admissions and Costs of Veterans Healthcare Delivered in Non-VHA Facilities
Get PDFThe purpose of this study is to identify admissions and costs of Veterans receiving care in non-VHA facilities. This study will focus on Veteran inpatient admissions in North Carolina (NC) during 2016. This study is an exploratory, quantitative work using historical archival data from HCUP. This study will give a detailed analysis of veteran demographics (age, gender, race), admission characteristics (admitting dx, total charges, length of stay (LOS), ICD 10 codes, and patient location (state, county). This study will guide VHA leadership in restructuring the Veterans Community Care Program
A Novel Platform for Multiplexed N-glycoprotein Biomarker Discovery for Hepatocellular Carcinoma by Antibody Panel Based N-glycan Imaging
Get PDFThe vast majority of biomarkers used in the detection of cancer are glycoproteins, and numerous studies have indicated that the N-glycosylation of serum glycoproteins changes with the development of hepatocellular carcinoma (HCC). However, current biomarkers for HCC are lacking in sensitivity and specificity, and there is a need for higher throughput techniques to discover more powerful biomarkers. The majority of methods that do analyze N-glycans and their protein carriers generally require large amounts of sample preparation and/or look at only one protein at a time, which is a barrier for translating discoveries to the clinic. In response to this need for multiplexed biomarker analysis of protein-specific N-glycan changes, we developed a novel platform for the simultaneous analysis of potentially 100s of N-linked glycoproteins from biofluids with the goal of discovering new clinically-relevant cancer biomarkers. This new mass spectrometry imaging platform for multiplexed N-glycoprotein biomarker was applied to multiple cohorts of cirrhotic and HCC patient serum samples. An antibody panel encompassing antibodies for seven glycoproteins was used in the analysis of two cohorts consisting of 100 patients. These data were used to create biomarker algorithms incorporating protein-specific glycan signatures and clinical information. These models produced AUROCs of 0.9289 and 0.9278 for differentiating HCC from cirrhosis, which were significant improvements on the currently used biomarker AFP. We also expect that this platform can be expanded for biomarker discovery of other types of cancers and diseases from numerous types of biofluids
Cost and Variations in Trauma Types for Pediatric ER Visits by South Carolina County
Get PDFChildren between the ages of 0 to 19 are treated in South Carolina emergency rooms (ER) and hospitals for unintentional injuries at an alarming rate which contributes to high medical cost and high mortality and morbidity rate. The objective of the study is to examine ER visits and hospital discharge data for pediatric patients in South Carolina by county to identify trauma types for unintentional injuries, cost, distribution by high-risk populations and by rural or urban classification to determine appropriate interventions. This is a quantitative study using retrospective analysis of archival data from ER visits and hospital discharge data for South Carolina by county for ages 0 to 19. HCUP databases and ICD-10 E-codes is used to identify study population for years 2016, 2017 and 2018. The mean and standard deviation for total charges and ER payments remained static over the three-years. Medicaid (55.1%) was the top payor across all payors. Males represented over 55% for each year studied. Blacks (48.2%) had a higher rate of injury events than all other race. The most common injury events were poisonings 10,467 (25.4%), natural/environmental 9,531 (23.1%) and falls 7,702 (18.7%). Counties with the highest risk percentage and most frequent injury events were Chester, Cherokee, Orangeburg, Williamsburg, Fairfield, Beaufort, and Georgetown counties
Role of Dynorphin/Kappa Opioid Receptor Activity within the Extended Amygdala in Binge Alcohol Drinking
Get PDFAlcohol Use Disorder (AUD) is a significant national and global public health problem. Of concern, binge drinking is the most common pattern of excessive alcohol consumption and serves as a risk factor for the development of AUD. Recent studies have implicated the dynorphin/kappa opioid receptor (DYN/KOR) neuropeptide system in this pattern of drinking but the precise circuitry mediating these effects are poorly understood. The central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) are two interconnected structures within the extended amygdala macrostructure that are rich in DYN/KOR and thought to contribute to binge drinking behavior. In the present studies, we demonstrate that KOR in the BNST contribute to excessive drinking by showing that site-specific delivery of a KOR antagonist decreased, while an agonist increased, binge-like alcohol consumption. Furthermore, we show that high levels of drinking induced by systemic administration of a KOR agonist were reversed by selective KOR blockade within the BNST. These findings suggest that KOR in the BNST promote binge drinking behavior, however, the endogenous dynorphinergic circuitry underlying this effect remains unknown. The CeA is a likely candidate in that it is involved in excessive drinking and sends dense dynorphinergic projections to the BNST (CeA-BNST-DYN+). In support of this hypothesis, we demonstrate that neuronal activity is increased within the CeA during a binge drinking session and that chemogenetic inhibition of the CeA-BNST-DYN+ pathway selectively decreased binge-like alcohol consumption. Collectively, these studies suggest that the CeA-BNST-DYN+ circuit contributes to binge-like alcohol consumption and KORs in the BNST likely mediate this effect. These studies provide valuable insight into neuronal circuitry underlying a key aspect of AUD and point to the DYN/KOR system as a potential therapeutic target for the treatment of excessive drinking
Mitigating the Risk of Financial Distress and Closure in Rural Hospitals: A Multiple Case Study
Get PDFFew studies have explored strategies rural hospitals have implemented to lower the risk of financial distress and closure. The objective of this doctoral project is to explore factors rural hospital stakeholders consider when determining the most appropriate business model for their organization. A multiple case study design was utilized to explore key factors considered in the decision-making processes at three rural hospitals in the southeastern Unites States with varying business models and characteristics. Nine rural hospital stakeholders including administrators, clinician, and community leaders participated in semi-structured interviews. Interviews were recorded, transcribed, and analyzed using an inductive coding process. Seven themes emerged: 1) Align hospital with community needs, 2) Rightsize services to address community needs, 3) Leverage collaboration and partnership, 4) Access to financial resources, 5) Leadership and governance, 6) Community awareness and engagement, and 7) Challenges with recruiting healthcare professionals. Findings suggest when determining the most appropriate business model to implement, rural hospital stakeholders should identify the specific needs of their surrounding community and redesign services to meet the needs while leveraging resources within and outside the community. Additionally, stakeholders should assess leadership and governance competencies and determine how to engage the community as active partners in the decision-making process
Effects of the Abused Inhalant Toluene on mPFC-Dependent Cognitive Behaviors and Associated Neural Activity
Get PDFVolatile organic solvents like toluene induce euphoria and intoxication when inhaled at high concentrations. Inhalant misuse is linked to behavioral, cognitive, and anatomical deficits in humans leading to a reduced productivity and quality of life. Yet, preclinical studies on the effect of inhalants on executive control in animal models are limited. We address this gap in knowledge using rodent models in two ways: first, by examining the long-lasting effects of repeated toluene inhalation during adolescence on several measures of executive function in adulthood and second, by studying the effects of acute toluene inhalation on risk/reward decision making and related neurocircuitry. Repeated inhalation of toluene during adolescence blunted acquisition of operant and Pavlovian learning in adulthood without affecting probabilistic discounting, progressive ratio breakpoint, latent inhibition or reversal learning. Acute toluene vapor inhalation, however, caused a dose-dependent, sex-independent deficit in behavioral flexibility during probabilistic discounting, a pattern that implicates dysfunctional medial prefrontal cortex (mPFC) activity. To address this hypothesis, we virally expressed the genetically encoded calcium sensor GCaMP6f in glutamatergic mPFC neurons and monitored calcium transients during during task performance using in vivo fiber photometry. Peaks in GCaMP6f activity shifted from pre-risky to pre-safe choice during contingency updating, an effect that was eliminated by acute toluene exposure. mPFC activity in toluene-treated animals also did not distinguish between risky/large wins and safe/small wins. Interestingly, previous studies from our lab demonstrated a toluene-induced long-term depression of AMPA-mediated synaptic activity in deep-layer mPFC neurons. This effect was dependent on endocannabinoids (EC) synthesis and presynaptic cannabinoid receptor (CB1R) function. Here, we found that pharmacological inhibition of CB1Rs in the mPFC or systemically did not mitigate toluene’s effect on probabilistic discounting. Behavioral flexibility in this task also depends on functional mPFC-basolateral amygdala (BLA) neurocircuitry. Electrophysiological interrogation of BLA neurons innervated by the mPFC using ex vivo slice electrophysiology and optogenetics revealed a CB1R-dependent decrease in excitatory synaptic transmission following toluene application. These data elucidate learning and behavioral flexibility deficits caused by toluene, including insights on potential mPFC-BLA- and CB1R-dependent mechanisms
Antibiotic Disruption of Oral Microbiota Dysregulates the Osteoimmune Response and Alveolar Bone Homeostasis in the Healthy Periodontium
Get PDFProblem: A balanced relationship between the host and oral microbiota supports periodontal health and alveolar bone homeostasis. Antibiotic perturbation of the gut microbiota critically regulates the osteoimmune response at non-oral skeletal sites. However, the impact of antibiotics on the oral microbiota and osteoimmune mechanisms regulating alveolar bone homeostasis are unknown. Considering that periodontitis driven bone loss is caused by dysbiotic shifts in the oral microbiome, antibiotic disruption of the oral microbiota may have deleterious effects on alveolar bone homeostasis. Approach: Drinking water of sex-matched C57BL/6T specific-pathogen-free (SPF) mice was supplemented with minocycline (MINO) or vehicle (VEH) control treatment from age 6 to 12 weeks. SPF mice were euthanized at age 12 weeks to assess immediate effects and at age 18 weeks to evaluate sustained minocycline effects. 16S rDNA analysis was performed to evaluate bacterial load and phylum level alterations in the oral microbiome. Micro-CT was utilized to assess linear alveolar bone loss in the maxilla and cortical/trabecular bone microarchitecture in the mandible. qRT-PCR analysis was carried out to assess pro-osteoclastic and pro-inflammatory genes in the mandible bone marrow (MBM) and gingiva. TRAP+ osteoclastic cell outcomes in alveolar bone were evaluated by in situ and in vitro approaches. Flow cytometric analysis of immune cells was performed in MBM and cervical lymph nodes (CLNs). In a separate experiment, drinking water of male C57BL/6T germ-free (GF) mice was supplemented with MINO or VEH treatment from age 6 to 12 weeks. Results: MINO treatment increased overall bacterial load and induced phylum level alterations in the oral bacteriome of 12-week-old male SPF mice. Disruption of phylum level bacterial communities were sustained in 18-week-old male SPF mice. The effects of MINO treatment on the oral microbiota were sex-dependent as no alterations were seen in female mice. MINO treatment induced linear alveolar bone loss in both male and female SPF mice at the age 12 weeks and these effects persisted at age 18 weeks. Validating that MINO-induced catabolic effects on alveolar bone is dependent on the oral microbiota, no differences were found in linear alveolar bone loss in MINO vs. VEH treated male GF mice. Cortical bone thickness was decreased in the mandible in response to MINO treatment. Osteoclast cell size and bone interface were increased in maxillary alveolar bone sections from MINO vs. VEH treated male SPF mice. Exogenous MINO stimulation in MBM cultures derived from naïve 12-week-old male SPF mice increased osteoclast size and number of nuclei. Intriguingly, these findings suggest that MINO-induced pro-osteoclastic effects could be in part independent of the microbiota. Pro-inflammatory plasmacytoid dendritic cells (DCs) were upregulated within MBM and CLNs of MINO vs. VEH treated male SPF mice. Paralleling the plasmacytoid DCs, MINO treatment profoundly increased TH1 and TH17 cell populations in the MBM and CLNs. Conclusion: The current investigation reveals that MINO disruption of oral microbiota induces a pro-inflammatory immune response, which upregulates osteoclastogenesis, and drives alveolar bone loss. This novel research shows that oral MINO therapy, a commonly prescribed antibiotic treatment, may have detrimental clinical effects on alveolar bone in the healthy periodontium
Examining Racial Differences in Privilege and Social Class: Use of a Modified Privilege Walk to Promote Discussions on Racial Disparities
No full textBackground: There is a need for more educational research focused on social determinants of health (SDOH), such as systemic racism and discrimination, and their impact on students as well as patients. Objective: To explore racial differences in privilege in undergraduate health care students regarding structural and intermediary social determinants of health. Methods: Two cohorts (2019 and 2020) of undergraduate pre-health professionals at the Medical University of South Carolina (MUSC) completed an MPW. Two-sample t-test were used for continuous data. Chi-square was used for categorical data. Unadjusted logistic regression models were completed to determine odds. Results: Data included 38 MPW participants. There was a significant difference in privilege scores between White students (16.5) and minority students (0.67) (p=0.0002). Minority students were significantly more likely to skip a meal compared to their counterparts. Conclusions: The survey data identified minority students, on average, experienced less privilege than their White counterparts. Minority students may face increased barriers that may negative impact their health and quality of life.https://medica-musc.researchcommons.org/posters/1024/thumbnail.jp