Digital Commons Network^™

Development And Comparison Of Risk-Adjusted Models To Benchmark Antibiotic Use In The University Healthsystem Consortium Hospitals, Omar Moh'd Musa Ibrahim

Theses and Dissertations

Background. Infectious diseases societies recommend that hospitals risk-adjust their antimicrobial use before comparing it to their peers, a process called benchmarking. The purpose of this investigation is to apply and compare 3 risk-adjustment procedures for benchmarking hospital antibacterial consumption (AbC). Two standardization of rates procedures, direct and indirect standardization, are compared with one another as well as with regression modeling. Methods. Total aggregate adult AbC for 52 systemic antibacterial agents was measured in 70 hospitals that subscribed to the University HealthSystem Consortium Clinical Resource Manager database in 2009 and expressed as days of therapy (DOTs) per either 1000 patients days …

An Agent Based Model Of Tumor Growth And Response To Radiotherapy, Nicole O'Neil

Theses and Dissertations

An agent based model was developed to examine the growth of a tumor in a healthy cell population. Response to radiation and impact of mutation and bystander effects were studied. In the growth model, the cancer cells proliferated outward becoming invasive. The mass of cancer cells developed a necrotic core. Various treatment protocols of radiation were compared. Timing of treatments was critical to the success of therapy. The event of mutation was rare. When mutation occurred, either unsuccessful treatment or re-growth could result. Multiple rounds of radiation potentially led to increased mutation. Low levels of the bystander effect had little …

Population Based Model Of Gonorrhea And Interventions Against Increased Antibiotic Resistance, Courtney Henry

Theses and Dissertations

Gonnorrhea is an infectious sexually transmitted disease (STD) caused by the bacterium Neisseria gonorrhoeae that commonly reproduces in the reproductive tract.The Centers of Disease Control and Prevention (CDC) estimate that more than 700,000 individuals in the U.S. contract new gonorrheal infections per year. During recent years, there has been a progressive global increase of drug-resistant strains of gonorrhea. Therefore, there exists the necessity for health organizations to encourage the monitoring, research and development of innovative treatment regimens. We have developed multiple mathematical models to explore the gonorrheal disease state. The first objective of model formulation was to fit the model …

Expression Of Foreign Genes In The Pseudomonas Bacteriophage Pf3, Krystin Weathers

Theses and Dissertations

Filamentous bacteriophages were engineered to express foreign genes with the ultimate purpose of displaying transmission control anti-malarial peptides as in phage display. It was hypothesized that expression of foreign genes would be possible using the phage’s promoters. This hypothesis was tested by assuming that promoters for the phage major coat protein (MCP) gene would also promote the expression of any foreign gene inserted downstream of the MCP gene. As proof of principle, the bacteriophages Pf3, Pf1, and M13 were engineered in this way to successfully synthesize Enhanced Green Fluorescent Protein (EGFP). Type 88 phage display on the EGFP recombinant Pf3 …

Engineering Of Polyamidoamine (Pamam) Dendrimers For Gene And Drug Delivery, Quan Yuan

Theses and Dissertations

Dendrimers are a class of polymers with a highly branched, three-dimensional architecture composed of an initiator core, several interior layers of repeating units and multiple surface groups. They have been recognized as the most versatile compositionally and structurally controlled nanoscale building blocks throughout the fields of engineering, materials science, chemistry, and biology, and they have been widely investigated for drug and gene delivery. Polyamidoamine (PAMAM) dendrimers have inherent properties for gene delivery because of their high buffering capacity, polycationic surface and numerous surface groups for biofunctionlization. This dissertation is organized into four independent sections. The first section investigates a series …

Semi-Interpenetrating Nanofiber Scaffolds For Transbuccal Drug Delivery, Donald Aduba Jr.

Theses and Dissertations

The oral buccal mucosa is a promising absorption site for drug administration because it is permeable, highly vascularized and allows ease of administration. Although there are many platforms that have been used for drug delivery, nanofiber scaffolds as a platform for local or systemic drug delivery through the oral mucosa have not been fully explored. In this thesis, we fabricated a biocompatible electrospun gelatin nanofiber scaffold for local drug delivery at the oral mucosa. To stabilize the electrospun gelatin nanofibers and allow non-invasive incorporation of therapeutics into the scaffold, photo-reactive polyethylene-glycol (PEG)-diacrylate was employed to crosslink the scaffold to form …

Assessing The Genotoxicity Of Triclosan In Tadpoles Of The American Bullfrog, Lithobates Catesbeianus., David Emery

Theses and Dissertations

Amphibians are particularly sensitive to environmental degradation and, therefore, serve as effective environmental quality indicators. Research has suggested that amphibian declines are exacerbated by manmade environmental toxicants, especially those found in high concentrations in urban areas. The NIH has pinpointed genotoxicity as a major route of cancer causation, and has since developed stringent testing procedures for potentially hazardous chemicals. One such method, recognized for its simplicity and economy, is the micronucleus assay. A study was conducted assessing the genotoxicity of the widely used antimicrobial agent Triclosan to American Bullfrog tadpoles. Lithobates catesbeianus tadpoles were reared in glass aquaria containing ultra-high …

The Effectiveness Of Visual Aids In Motivational Counseling On Oral Health Literacy, Christian Peck

Theses and Dissertations

Purpose: The purpose of this study is to determine if motivational interviewing with written/illustrated infant oral health education provided to caregivers of pediatric dental patients increases caregivers’ oral health literacy compared to verbal only motivational instruction. Methods: This is a cohort study of caregivers and their child receiving oral health anticipatory guidance utilizing motivational interviewing with and without visual aids. Caregivers (N=20) of pediatric dental patients age 0-4 that presented to the Virginia Commonwealth University School of Dentistry for a new patient exam were recruited for the study. Caregivers were randomly assigned into 2 groups: the intervention group (IG), and …

Effect Of Local Anesthesia On Postoperative Pain With General Anesthesia, Belinda Campbell

Theses and Dissertations

Purpose: The aim of this study was to determine if the use of local anesthesia with general anesthesia results in less postoperative pain. The alternative hypothesis is that children will experience less postoperative discomfort when utilizing intraligamental local anesthetic during the intra-operative time period. Methods: Patients were recruited for this single blind, randomized, prospective cohort study with the following inclusion criteria: English speaking children age 3-6 years, ASA I/II requiring general anesthesia for dental treatment. Randomization was done to place patients in groups of no local anesthetic vs. local anesthetic administration. A Wong-Baker Faces Pain Scale was utilized to evaluate …

Exploring The Social Determinants Of Sexually Transmitted Disease And High-Risk Sexual Behaviors, River Pugsley

Theses and Dissertations

Abstract 1: A multi-level assessment of disproportionate population sex ratios and high-risk sexual behaviors among STD clinic patients Low male-to-female sex ratios in a population may influence high-risk sexual behaviors, such as multiple sex partners and inconsistent condom use, which facilitate the transmission of STDs. This study used multi-level modeling to assess whether population sex ratios were associated with these two individual-level behaviors. All analyses were stratified by gender. Interview data were collected from patients (N = 9,203, 48% male) attending participating STD clinics. Interviews included information on socio-demographics and sexual behavior, including number of sex partners in the previous …

Utilization Patterns Of Iv Iron And Erythropoiesis Stimulating Agents In Anemic Chronic Kidney Disease Patients: A Multihospital Study, Avani D. Joshi, David A. Holdford, Donald F. Brophy, Spencer E. Harpe, Darcy Mays, Todd W. B. Gehr

Pharmacotherapy and Outcomes Science Publications

Intravenous (IV) iron and Erythropoiesis Stimulating Agents (ESAs) are recommended for anemia management in chronic kidney disease (CKD). This retrospective cohort study analyzed utilization patterns of IV iron and ESA in patients over 18 years of age admitted to University Health System Hospitals with a primary or secondary diagnosis of CKD between January 1, 2006 to December 31, 2008. A clustered binomial logistic regression using the GEE methodology was used to identify predictors of IV iron utilization. Only 8% (n = 6678) of CKD patients on ESA therapy received IV iron supplementation in university hospitals. Those receiving iron used significantly …

Spxa1 Involved In Hydrogen Peroxide Production, Stress Tolerance And Endocarditis Virulence In Streptococcus Sanguinis, Lei Chen, Xiuchun Ge, Xiaojing Wang, Jenishkumar R. Patel, Ping Xu

Philips Institute for Oral Health Research Publications

Streptococcus sanguinis is one of the most common agents of infective endocarditis. Spx proteins are a group of global regulators that negatively or positively control global transcription initiation. In this study, we characterized the spxA1 gene in S. sanguinis SK36. The spxA1 null mutant displayed opaque colony morphology, reduced hydrogen peroxide (H2O2) production, and reduced antagonistic activity against Streptococcus mutans UA159 relative to the wild type strain. The ΔspxA1 mutant also demonstrated decreased tolerance to high temperature, acidic and oxidative stresses. Further analysis revealed that ΔspxA1 also exhibited a ~5-fold reduction in competitiveness in an animal model of …

Toothbrush Contamination: A Review Of The Literature, Michelle R. Frazelle, Cindy L. Munro

School of Nursing Publications

Toothbrushes are commonly used in hospital settings and may harbor potentially harmful microorganisms. A peer-reviewed literature review was conducted to evaluate the cumulative state of knowledge related to toothbrush contamination and its possible role in disease transmission. A systematic review was conducted on adult human subjects through three distinct searches. The review resulted in seven experimental and three descriptive studies which identified multiple concepts related to toothbrush contamination to include contamination, methods for decontamination, storage, design, and environmental factors. The selected studies found that toothbrushes of healthy and oral diseased adults become contaminated with pathogenic bacteria from the dental plaque, …

A Program For Sustained Improvement In Preventing Ventilator Associated Pneumonia In An Intensive Care Setting, Raquel A. Caserta, Alexandre R. Marra, Marcelino S. Durão, Cláudia Vallone Silva, Oscar Fernando Pavao Dos Santos, Henrique Sutton De Sousa Neves, Michael B. Edmond, Karina Tavares Timenetsky

Internal Medicine Publications

Background Ventilator-associated pneumonia (VAP) is a common infection in the intensive care unit (ICU) and associated with a high mortality.

Methods A quasi-experimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize VAP prevention were performed from October 2008 to December 2010. All of these processes, including the Institute for Healthcare Improvement’s (IHI) ventilator bundle plus oral decontamination with chlorhexidine and continuous aspiration of subglottic secretions (CASS), were adopted for patients undergoing mechanical ventilation.

Results We evaluated a total of 21,984 patient-days, and a total of 6,052 ventilator-days (ventilator utilization rate of 0.27). We found VAP rates of …

Inflammation, Coagulation And Cardiovascular Disease In Hiv-Infected Individuals, Daniel A. Duprez, Jacqueline Neuhaus, Lewis H. Kuller, Russell Tracy, Waldo Belloso, Stephane De Wit, Fraser Drummond, H. Clifford Lane, Bruno Ledergerber, Jens Lundgren, Daniel Nixon, Nicholas I. Paton, Ronald J. Prineas

Internal Medicine Publications

Background

The SMART study was a trial of intermittent use of antiretroviral therapy (ART) (drug conservation [DC]) versus continuous use of ART (viral suppression [VS]) as a strategy to reduce toxicities, including cardiovascular disease (CVD) risk. We studied the predictive value of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and mortality in HIV-infected patients who were enrolled in SMART beyond other measured CVD risk factors.

Methods

A blood sample was available in 5098 participants who were enrolled in the SMART study for the measurement of IL-6, hsCRP and D-dimer. Hazard ratios (HR) with 95% CI …

Catheter Related Bloodstream Infection (Cr-Bsi) In Icu Patients: Making The Decision To Remove Or Not To Remove The Central Venous Catheter, Rodrigo O. Deliberato, Alexandre R. Marra, Thiago D. Correa, Marines D. V. Martino, Luci Correa, Oscar Fernando Pavao Dos Santos, Michael B. Edmond

Internal Medicine Publications

Background

Approximately 150 million central venous catheters (CVC) are used each year in the United States. Catheter-related bloodstream infections (CR-BSI) are one of the most important complications of the central venous catheters (CVCs). Our objective was to compare the in-hospital mortality when the catheter is removed or not removed in patients with CR-BSI.

Methods

We reviewed all episodes of CR-BSI that occurred in our intensive care unit (ICU) from January 2000 to December 2008. The standard method was defined as a patient with a CVC and at least one positive blood culture obtained from a peripheral vein and a positive …

Developing Clinical Practice Guidelines: Target Audiences, Identifying Topics For Guidelines, Guideline Group Composition And Functioning And Conflicts Of Interest, Martin P. Eccles, Jeremy M. Grimshaw, Paul Shekelle, Holger J. Schünemann, Steven H. Woolf

Family Medicine and Population Health Publications

Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the …

Treatment For Schistosoma Japonicum, Reduction Of Intestinal Parasite Load, And Cognitive Test Score Improvements In School-Aged Children, Amara E. Ezeamama, Stephen T. Mcgarvey, Joseph Hogan, Kate L. Lapane, David C. Bellinger, Luz P. Acosta, Tjalling Leenstra, Remigio M. Olveda, Jonathan D. Kurtis, Jennifer F. Friedman

Family Medicine and Population Health Publications

Background

To determine whether treatment of intestinal parasitic infections improves cognitive function in school-aged children, we examined changes in cognitive testscores over 18 months in relation to: (i) treatment-related Schistosoma japonicum intensity decline, (ii) spontaneous reduction of single soil-transmitted helminth (STH) species, and (iii) ≥2 STH infections among 253 S. japonicum-infected children.

Methodology

Helminth infections were assessed at baseline and quarterly by the Kato-Katz method. S. japonicum infection was treated at baseline using praziquantel. An intensity-based indicator of lower vs. no change/higher infection was defined separately for each helminth species and joint intensity declines of ≥2 STH species. In …

Identification And Characterization Of A Novel Calcium-Activated Apyrase Fromcryptosporidium Parasites And Its Potential Role In Pathogenesis, Patricio A. Manque, Ute Woehlbier, Ana M. Lara, Fernando Tenjo, João M. Alves, Gregory A. Buck

Microbiology and Immunology Publications

Herein, we report the biochemical and functional characterization of a novel Ca2+-activated nucleoside diphosphatase (apyrase), CApy, of the intracellular gut pathogen Cryptosporidium. The purified recombinant CApy protein displayed activity, substrate specificity and calcium dependency strikingly similar to the previously described human apyrase, SCAN-1 (soluble calcium-activated nucleotidase 1). CApy was found to be expressed in both Cryptosporidium parvum oocysts and sporozoites, and displayed a polar localization in the latter, suggesting a possible co-localization with the apical complex of the parasite. In vitro binding experiments revealed that CApy interacts with the host cell in a dose-dependent fashion, implying the presence of …

Cpg And Interleukin-15 Synergize To Enhance Ifn- Production By Activated Cd8+ T Cells, Dustin Cobb, Siqi Guo, Ronald B. Smeltz

Microbiology and Immunology Publications

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8+ T cells. Paradoxically, we previously reported that IL-15 could enhance CD8+ T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8+ T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN- by CD8+ T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN- production. The effect of CpG and IL-15 was also evident with CD8+ T …

Virginia Commonwealth University Graduate And Professional Programs Bulletin Courses [2012], Virginia Commonwealth University

VCU Bulletins

Listing of professional and graduate courses for 2012-2013

Minocycline Modulates Antigen-Specific Ctl Activity Through Inactivation Of Mononuclear Phagocytes In Patients With Htlv-I Associated Neurologic Disease, Yoshimi Enose-Akahata, Eiji Matsuura, Yuetsu Tanaka, Unsong Oh, Steven Jacobson

Neurology Publications

Background The activation of mononuclear phagocytes (MPs), including monocytes, macrophages and dendritic cells, contributes to central nervous system inflammation in various neurological diseases. In HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), MPs are reservoirs of HTLV-I, and induce proinflammatory cytokines and excess T cell responses. The virus-infected or activated MPs may play a role in immuneregulation and disease progression in patients with HTLV-I-associated neurological diseases.

Results Phenotypic analysis of CD14+ monocytes in HAM/TSP patients demonstrated high expression of CX3CR1 and HLA-DR in CD14lowCD16+ monocytes, compared to healthy normal donors (NDs) and asymptomatic carriers (ACs), and the production of TNF-α and IL-1β in …

Bacterial Artificial Chromosome Clones Of Viruses Comprising The Towne Cytomegalovirus Vaccine, Xiaohong Cui, Stuart P. Adler, Andrew J. Davison, Larry Smith, El-Sayed E. Habib, Michael A. Mcvoy

Pediatrics Publications

Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we …

A Comparison Of Two Distinct Murine Macrophage Gene Expression Profiles In Response To Leishmania Amazonensis Infection, Christian M. Probst, Rodrigo A. Silva, Juliana P.B. Menezes, Tais F. Almeida, Ivana N. Gomes, Andréia C. Dallabona, Luiz S. Ozaki, Gregory A. Buck, Daniel P. Pavoni, Marco A. Krieger, Patrícia S.T. Veras

Study of Biological Complexity Publications

Background

The experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite.

Results

The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as …

Pcr Detection Of Malaria Parasites In Desiccated Anopheles Mosquitoes Is Uninhibited By Storage Time And Temperature, Mark A. Rider, Brian D. Byrd, Joseph Keating, Dawn M. Wesson, Kevin A. Caillouet

Biostatistics Publications

Background

Reliable methods to preserve mosquito vectors for malaria studies are necessary for detectingPlasmodium parasites. In field settings, however, maintaining a cold chain of storage from the time of collection until laboratory processing, or accessing other reliable means of sample preservation is often logistically impractical or cost prohibitive. As the Plasmodium infection rate of Anophelesmosquitoes is a central component of the entomological inoculation rate and other indicators of transmission intensity, storage conditions that affect pathogen detection may bias malaria surveillance indicators. This study investigated the effect of storage time and temperature on the ability to detect Plasmodium parasites …

Patient- And Population-Level Health Consequences Of Discontinuing Antiretroviral Therapy In Settings With Inadequate Hiv Treatment Availability, April D. Kimmel, Stephen C. Resch, Xavier Anglaret, Norman Daniels, Sue J. Goldie, Christine Daniel, Angela Y. Wong, Kenneth A. Freedberg, Milton C. Weinstein

Health Policy Publications

Background

In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes.

Methods

In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the …

The Interdomain Linker Of Aav-2 Rep68 Is An Integral Part Of Its Oligomerization Domain: Role Of A Conserved Sf3 Helicase Residue In Oligomerization, Francisco Zarate-Perez, Martino Bardelli, John W. Burgner Ii, Maria Villamil-Jarauta, Kanni Das, Demet Kekilli, Jorge Mansilla-Soto, R. Michael Linden, Carlos R. Escalante

Physiology and Biophysics Publications and Presentations

The four Rep proteins of adeno-associated virus (AAV) orchestrate all aspects of its viral life cycle, including transcription regulation, DNA replication, virus assembly, and site-specific integration of the viral genome into the human chromosome 19. All Rep proteins share a central SF3 superfamily helicase domain. In other SF3 members this domain is sufficient to induce oligomerization. However, the helicase domain in AAV Rep proteins (i.e. Rep40/Rep52) as shown by its monomeric characteristic, is not able to mediate stable oligomerization. This observation led us to hypothesize the existence of an as yet undefined structural determinant that regulates Rep oligomerization. In this …

Predictors Of Carbapenem Resistant Gram-Negative Bacteria In A Consortium Of Academic Medical Center Hospitals, Mera Ababneh

Theses and Dissertations

Background: Gram-negative resistance is a growing problem worldwide. It is generally believed that rates of resistant bacteria within a hospital are a function of antibiotic use, resistant organisms brought into the hospital, infection control efforts, and underlying severity of patient illness. The relative contribution of each to a particular resistance phenotype is unclear. P. aeruginosa is responsible for many hospital acquired infections and it may become resistant to carbapenems. In addition, newer threats to the future utility of the carbapenems are carbapenemase-producing K. pneumoniae Purpose: To determine if there is an association between the volume and composition of antibiotic use, …

Response To And Recovery From Endotracheal Suctioning In Preterm Infants Using Routine Versus Four-Handed Care, Sharon Cone

Theses and Dissertations

Neonatal Intensive Care Units have experienced profound advances in technology and treatment modalities over the last two decades. Infants born at the edge of viability are now surviving despite prolonged hospitalizations. These infants born preterm are prone to a high degree of stress from life sustaining and routine interventions. Much focus has been directed toward addressing noxious environmental factors such as noise, light, and infectious disease; however, little has been done to examine the stress experienced by the professional caregiver who work in these environments. Environmental press theory, which focuses on the interplay between human beings and their surroundings, is …

Healthcare Acquired Infection Risk And Toothbrush Contamination In The Icu., Michelle Frazelle

Theses and Dissertations

Healthcare acquired infections (HAIs) are a complex and multi-factorial problem associated with high morbidity, mortality, and cost. Toothbrushes (TBs) may be at risk for contamination with potential pathogenic microorganisms (PPMs) from the patient care environment or autoinnoculation from the patient. We focused on three PPMs: multiply resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE), and Acinetobacter. Specific aims were to (1) describe environmental factors associated with TB contamination in the ICU; (2) describe the relationship between TB contamination and oral colonization in critically ill adults.