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Resource Use Trends by Medical Students at an Academic Medical Center in the 3rd and 4th Clerkship Years
Get PDFFailure of Primary Total Knee Arthroplasty: Establishing a Baseline for Retrieval Analysis Using Well-Functioning Necropsy Specimens
Get PDFIntroduction. Total knee arthroplasty (TKA) is an effective treatment for end-stage osteoarthritis of the knee. While many patients have positive functional and pain outcomes following primary TKA, a subset of patients have suboptimal outcomes, such as unexplained pain or aseptic loosening of the implant components necessitating revision of the index procedure. The understanding of the exact etiology of these suboptimal outcomes of primary TKA is in its infancy. In order to elucidate the etiology of failure in primary TKAs, a baseline for the factors contributing to arthroplasty failure and dissatisfaction must first be established. The purpose of this study was to investigate the relationship between soft tissue laxity, inflammatory cytokine concentrations, tissue metal concentrations, and wear scores of well-functioning implants retrieved from cadaveric specimens to determine the role of each of these factors in implant survivorship. It was hypothesized that decreased joint laxity would increase metal concentrations in the periprosthetic tissue, that cytokines specifically tied to the innate immune system would be elevated in laxer joints, and, lastly, that elevated inflammatory cytokines in the synovial fluid would be associated with elevated periprosthetic tissue metal concentrations.
Methodology. A total of 33 cadaveric specimens with primary TKA were obtained from two sources, the Medical Education and Research Institute (Memphis, TN) and RestoreLife USA (Elizabethton, TN), as part of institution review board approved multi-institutional orthopaedic retrieval program. Prior to testing and retrieval, fluoroscopically-assisted radiographs were taken to assess if any evidence of radiolucencies were present and all replacements were determined to be well-fixed per the images. Synovial fluid was then aspirated from the joint, processed, and stored in a -80˚C freezer. Each specimen was mounted into a custom knee testing platform and the IE rotation, varus-valgus (VV) deflection, and AP translation was measured at 0˚, 30˚, 60˚, and 90˚ of flexion. After collection of the laxity data, tissue samples were collected from the supra- and infra-patellar regions, the medial and lateral gutter, and from the tibia. The polyethylene inserts were assessed for wear on the condylar, backside, and stabilizing post surfaces, when applicable, and the femoral condyle was assessed for damage. A bead-based multiplex assay using the Luminex MAGPIX platform (R&D Systems, Minneapolis, MN) was performed on the synovial aspirates for simultaneous detection of various inflammatory cytokines including: IL-1β, IL-6, MCP-1, and MIP-3α. Inductively coupled plasma mass spectrometry (ICP-MS) was performed at Brooks Applied Labs (Bothel, WA) on the periprosthetic tissue samples for determination of tissue cobalt (Co), chromium (Cr), and titanium (Ti) concentrations. Finally, statistical analysis was conducted using SigmaPlot (Systat Software, Chicago, IL) to elucidate whether any correlations existed between the aforementioned factors.
Results. Decreased IE laxity at full extension was inversely correlated with increased Co concentrations in the periprosthetic tissues (ρ=-0.64, p=0.02) with a sample size (n) of 13 and a 95% confidence interval (CI) from -0.88 to -0.14. At 90° of flexion, anterior laxity was inversely correlated with Co concentrations (ρ=-0.66, p=0.03, n=11, 95% CI: -0.90 vi to -0.10). At 60° of flexion, anterior laxity was inversely correlated with Cr concentrations (ρ=-0.63, p=0.03, n=13, 95% CI: -0.88 to -0.12). Anterior laxity at 90° of flexion was also inversely correlated with Cr concentrations (ρ=-0.81, p=0.003, n=11, 95% CI: -0.95 to -0.41). Lastly, posterior laxity at 90° of flexion was inversely correlated with Cr concentrations in the periprosthetic tissues (ρ=-0.74, p=0.01, n=11, 95% CI: -0.93 to -0.25). At 60° of flexion, IE rotational laxity was inversely correlated with IL-1β concentrations (ρ=-0.55, p=0.02, n=18, 95% CI: -0.81 to -0.11). At 60° of flexion, VV laxity was inversely correlated with TNF-α concentrations (ρ=-0.78, p=2x10-4 , n=14, 95% CI -0.93 to -0.43). Additionally, VV laxity was inversely correlated with IL-1β concentrations (ρ=-0.48, p=0.04, n=18, 95% CI: -0.77 to -0.02) at 60° of flexion. At full extension, VV laxity was inversely correlated with IL-6 concentrations (ρ=-0.46, p=0.04, n=19, 95% CI: -0.76 to -0.01). Anterior laxity was directly correlated with IL-6 concentrations (ρ=0.53, p=0.02, n=18, 95% CI: 0.08 to 0.80) at 90° of flexion. Additionally, anterior laxity was directly correlated with MCP-1 concentrations (ρ=0.62, p=0.006, n=18, 95% CI: 0.22 to 0.84) at 90° of flexion. Cr was inversely correlated with IL-6 (ρ=-0.52, p=0.01, n=21, 95% CI: -0.78 to -0.11). Cr was also inversely correlated with MIP-3α (ρ=-0.46, p=0.04, n=21, 95% CI: -0.74 to -0.04).
Discussion. The specimens included in this study consisted of primary TKA implants that were retrieved at necropsy and were determined to be well-fixed per fluoroscopic analysis. The first objective of this study was to establish a baseline of different factors that likely contribute to failure of primary total knee replacements. This study provided semi-quantitative assessment of wear of the condylar surface, backside surface, and stabilizing post, when applicable, and of damage to the bearing surface of the femoral components. Joint laxity was measured using a custom knee testing platform that had been previously studied and utilized in published journal articles and theses. Inflammatory cytokine profiles in the synovial fluid samples were presented and measureable levels of metal debris was found in the periprosthetic tissue samples. The second objective of this study was to determine if any significant relationships arose in correlation analysis of the latter three aforementioned factors. An inverse trend was observed between joint laxity and tissue metal concentrations, such that decreased laxity induced metal release from the implant components. A direct trend was observed specifically between increased anteroposterior laxity and elevated inflammatory cytokines. Lastly, an inverse trend was found between decreased tissue metal concentrations and increased inflammatory cytokines. The third, and future, objective of this study is to utilize these measurements and observations for comparison with failed implants retrieved at time of revision. While some meaningful relationships were observed in this study, there were several limitations that must be noted. Firstly, this study had a relatively small sample size. Secondly, the cohort included a wide range of implants including cruciate-retaining, posterior-stabilized, fixed bearing, mobile bearing, monoblock, and modular designs fabricated from different material
Characterization of the Hepatotoxicity of Rifampicin and Isoniazid
Get PDFIn a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase of protoporphyrin ix (PPIX), the penultimate heme precursor. Excess PPIX is believed to bind to bile acids, precipitate in bile canaliculi, and form bile plugs leading to cholestasis fol owed by liver injury. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to up-regulate Alas1 but down-regulate Fech protein levels in mice; however the mechanism of isoniazid mediated heme synthesis disruption has remained unclear. Interestingly, metabolites of isoniazid, pyridoxal isonicotinoyl hydrazone (PIH, the isoniazid and vitamin B6 conjugate) and hydrazine, have been detected in the urine of humans treated with isoniazid previously. Here I show that in primary human hepatocytes and the human hepatocellular carcinoma cell line HepG2/C3A: (1) the physiochemical properties of PPIX may contribute to toxicity (2) isoniazid treatment results in an increase of ALAS1 but a decrease in FECH protein levels by Western blot analysis; (3) hydrazine treatment up-regulates ALAS1 protein and mRNA levels; (4) PIH treatment decreases FECH protein levels; (5) PIH is detected by mass spectrometry analysis following isoniazid treatment with a further increase when exogenous vitamin B6 analogues are co-administrated. In addition, the (6) PIH mediated down-regulation of human FECH is dependent on iron levels. Proteomics profiling analysis suggests that in the livers of hPXR mice (7) rifampicin may induce CYP450 changes associated with increased hydrazine reactivity with cellular proteins, (8) multiple [2Fe-2S]-containing proteins and (9) [Fe-S] assembly machinery proteins may be down-regulated in mice due to isoniazid. Together these data demonstrate that hydrazine up-regulates ALAS1 while PIH down-regulates FECH, suggesting that the metabolites of isoniazid mediate its disruption of heme biosynthesis
Telehealth in Rural Tennessee- Closing the Gap in Care?
Get PDFTelehealth is quickly becoming a tool used in everyday healthcare. Certain areas, such as rural communities in Tennessee, experience health disparities because of their location and distance from health care providers. This gap in care can be diminished through the use of telehealth services. This research project is taking place to gather data from hospitals in Tennessee currently providing telehealth services. I want to determine if telehealth is closing the gap-in-care seen in rural communities. Through research, I have found there are multiple barriers to telehealth, but also significant benefits. I think with additional education and training, telehealth can become a strong resource for individuals in all communities
Health Information Technology and Language Barriers in Pre-Admission Clinics
Get PDFLEP or Limited English Proficiency patients across the United States are at higher risk for decreased quality of care because of their inability to communicate effectively with healthcare providers. Interpreters are not offered in a consistent manner due to many variables such as cost, availability of qualified interpreters, the time spent with patients due to an increased work-overload and clinician lack of knowledge into technologies available to use. Healthcare information technology such as video and telephone interpretation can bridge the gap between patients and medical personnel when a language barrier is present. At the pre-admission clinic, the Nursing personnel interviews the patient and assesses the need for an interpreter. All patients scheduled for an appointment at the pre-admission clinic will undergo a scheduled surgery or procedure that will require General Anesthesia, Epidural blocks or the administration of Local Monitored Anesthesia Care. The purpose of this paper is to determine the practices of Nurses in these initial interactions, regarding communication, technology, and documentation in the Electronic Health Record through a qualitative survey
Understanding the Impact of BCRP and PGP Efflux Transporters on the Disposition of Their Endogenous, Xenobiotic and Dietary Substrates
Get PDFBreast Cancer Resistant Protein (BCRP) and P-glycoprotein (PGP) are membrane-bound efflux transporters that transport multiple chemical classes of compounds and act as barriers to tissue permeability, thereby regulating tissue exposure of their substrates. The role of these transporters in therapeutic resistance of their xenobiotic substrates due to their expression and efflux function at target organs/tissues, especially in brain and intestine, is well established, which has fueled investigation toward identification of their inhibitors. Multiple clinically used drugs and dietary chemicals have been reported to inhibit these transporters and potentially increase the exposure of concomitantly administered BCRP and/or PGP substrates, which might be desirable (to increase efficacy of the substrate drug) as well as undesirable (as it can affect the disposition of the substrate in tissues where it might cause toxicity). Therefore, drug-drug and food-drug interactions with BCRP and PGP are a major concern in drug development, as recognized by US Food and Drug Administration (FDA), European Medicines Agency (EMA) and International Transporter Consortium (ITC).
BCRP and PGP transporters are also known to transport endogenous substrates and have been associated with important physiological functions. This includes an inflammatory bowel disease-like phenotype associated with a non-functional PGP polymorphism (Ala893), while a loss of function mutation in BCRP (Q141K) is known to be positively associated with gout and negatively associated with Parkinson’s syndrome. Although a few endogenous substrates of BCRP and PGP have been identified, a systemic understanding of their physiological function and effect on the endogenous metabolome is still lacking.
In the current studies, utilizing untargeted metabolomics, coupled with transcriptomic analysis, we sought to understand the endogenous function of Bcrp and/Pgp transporters in rats, by comparing the plasma and cerebrospinal fluid metabolome of wild-type and Bcrp-Pgp double knockout rats. Our findings revealed several putative novel endogenous/dietary substrates of Bcrp and Pgp transporters and established a novel understanding of the physiological function of these transporters. We also identified the anesthetic/analgesic ketamine as a putative substrate of Bcrp and Pgp, and found that ketamine pharmacokinetics (PK), as well as pharmacodynamics (PD), are affected by these efflux transporters. Importantly, the Bcrp-Pgp inhibitor, elacridar, was found to alter the PD of ketamine, indicating that ketamine might be prone toward drug-drug interactions (DDIs) associated with Bcrp-Pgp inhibitors. Finally, utilizing a Bcrp dietary substrate, Pheophorbide A (PhA), we developed an in vivo assay for the assessment of DDI due to inhibition of Bcrp at enterocytes. Our results demonstrated that PhA can be potentially used to create a reliable, high-throughput and less expensive in vivo assay for determining Bcrp-mediated DDIs
Medical Libraries of Tomorrow: Exploring New Acquisition Methods for E-Textbook Reference Collection Titles
Get PDFObjective: Acquiring new individual e-textbook titles at the Florida International University (FIU) Herbert Wertheim College of Medicine (HWCOM) Medical Library: The current method needs to be reconsidered?
Introduction: The Course Textbook Reference Collection has annually prepared for HWCOM programs based on the course textbook lists from each program coordinator. Librarians are always required to first look for textbooks in an electronic format:
HWCOM Library = Nearly 100% digital
Limited space for print copies
Clinical teaching sites -across the South Florida region
However, searching a specific e-book title is challenging.
Methods: A review and analysis of e-textbook acquisition activity records from the past two academic years (2017-2018 and 2018-2019)
The Early Steps Project: Occupational Therapy in a Pediatric Primary Care Setting
Get PDFThe purpose of this study is expand on the Early STEPs project goal of identifying early developmental delays in infants and young children in a health disparate population and to collect preliminary data to lay the groundwork for a future NIH grant proposal. Individuals with less education have poor health and shorter life expectancies than well-educated individuals, and research reveals that poverty is directly related to limited education. An innovative approach is needed to overcome barriers, improve health literacy, and educate parents on effective parenting strategies for this population. Technology may be the part of the solution to this issue. Through Early STEPs, the occupational therapists will continue to refer families to early intervention and therapy services as appropriate and follow-up to ensure that services are initiated. The OT will also determine if the parents are utilizing the Word Gap App and other provided resources to support their child\u27s development and to manage their stress. By increasing parental awareness and knowledge of language and motor skill development, the environments of underserved children will be enriched and parental stress will be reduced so that these children can have improved health and reach their full potential
Primary Care Practices’ Progress of Using Electronic Health Information Exchange (HIE)
Get PDFNow that EHRs are purportedly fully implemented in the healthcare industry, it is important to evaluate the electronic Health Information Exchange (HIE) between primary care facilities, laboratories, hospitals, specialists, regional coops, and public health authorities.
Meaningful Use Stage 3 implementation is to begin this year, 2018. Complementing this implementation, the Medicare Access and CHIP Reauthorization Act, MACRA, was signed into law on April 16, 2015. MACRA removes eligible clinicians from EHR Incentive Programs that were previously established by the HITECH Act. MACRA also creates the Quality Payment Program that the CMS will use for Medicare and Medicaid reimbursement to primary care providers. This payment program rewards clinicians for value over volume. The amount of reimbursement the CMS pays out is dependent on performance markers deemed as quality patient care. Electronic HIE directly affects a clinicians ability to achieve these performance markers.
This research study assesses the progress that primary care practices have had in reaching full spectrum industry electronic health information exchange. It will answer the question; does primary care practices electronically connect with their local laboratories, hospitals and regional data collecting entities. Additionally, the barriers that prevent electronic health information exchanged and interoperability between primary care practices and other medical professionals outside their organization will be analyzed. This study focus is limited to primary care providers