Pharmaceutical Preparations Commons^™

Survival Of A Serotype 4b Strain And A Serotype 1/2a Strain Of Listeria T Monocytogenes, Isolated From A Stone Fruit Outbreak Investigation, On Whole Stone Fruit At 4 °C, Antonio J. De Jesus, Ishani Sheth, Hee Jin Kwon, Zhujun Gao, Jessica Palmer, Minji Hur, Thomas S. Hammack, Dumitru Macarisin, Yi Chen

United States Food and Drug Administration: Publications

In the summer of 2014, a multistate outbreak of listeriosis associated with contaminated stone fruit (peach and nectarine) was reported. A serotype 4b variant Listeria monocytogenes (Lm) strain of singleton Sequence Type (ST) 382 was isolated from clinical samples and stone fruit associated with the outbreak. A serotype 1/2b Lm strain of ST5, Clonal Complex 5 was isolated only from outbreak-associated stone fruit, not from clinical samples. Here we investigated the fate of the serotype 4b and 1/2b strains, at two inoculation levels (high level at 3.7 logCFU/fruit and low level at 2.7 logCFU/fruit), on the surfaces of white peach, …

Adult Perceptions Of The Relative Harm Of Tobacco Products And Subsequent T Tobacco Product Use: Longitudinal Findings From Waves 1 And 2 Of The Population Assessment Of Tobacco And Health (Path) Study, Tara Elton-Marshall, Pete Driezen, Geoffrey T. Fong, K. Michael Cummings, Alexander Persoskie, Olivia Wackowski, Kelvin Choi, Annette Kaufman, David Strong, Shannon Gravely, Kristie Kristie, Jonathan Kwan, Maansi Bansal-Travers, Mark Travers, Andrew Hyland

United States Food and Drug Administration: Publications

Objectives: To examine: (1) How perceptions of harm for seven non-cigarette tobacco products predict sub- sequent use; (2) How change in use is associated with changes in perceptions of product harm; (3) Whether sociodemographic variables moderate the association between perceptions and use.

Methods: Data are from the adult sample (18+) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal cohort survey conducted September 2013-December 2014 (Wave 1 (W1) n = 32,320) and October 2014-October 2015 (Wave 2 (W2) n = 28,362).

Results: Wave 1 users and non-users of e-cigarettes, filtered cigars, cigarillos, and pipes, who …

An Evaluation Of The Usda's Policy To Reduce Listeria Illnesses In Ready‐To‐Eat Meat And Poultry Products, Travis Minor, Matt Parrett

United States Food and Drug Administration: Publications

Using 1998–2008 data collected by the Centers for Disease Control and Prevention on foodborne illnesses and outbreaks, we examine the economic impact of the United States Department of Agriculture's proposed and final rules to reduce the incidence of Listeria monocytogenes (Lm) in ready‐to‐ eat meat and poultry products. Using a difference‐in‐ differences approach, we find that these rules together reduced meat‐related Lm illnesses by about 60 per year, which we attribute to reductions in both the number and average size of meat‐related Lm outbreaks. We then monetize this illness reduction using an underreporting and underdiagnosis multiplier of 2.3 and an …

Genomics-Based Re-Examination Of The Taxonomy And Phylogeny Of Human And Simian Mastadenoviruses: An Evolving Whole Genomes Approach, Revealing Putative Zoonosis, Anthroponosis, And Amphizoonosis, June Kang, Ashrafali Mohamed Ismail, Shoaleh Dehghan, Jaya Rajaiya, Marc W. Allard, Haw Chuan Lim, David W. Dyer, James Chodosh, Donald Seto

United States Food and Drug Administration: Publications

With the advent of high-resolution and cost-effective genomics and bioinformatics tools and methods contributing to a large database of both human (HAdV) and simian (SAdV) adenoviruses, a genomics-based re-evaluation of their taxonomy is warranted. Interest in these particular adenoviruses is growing in part due to the applications of both in gene transfer protocols, including gene therapy and vaccines, as well in oncolytic protocols. In particular, the re-evaluation of SAdVs as appropriate vectors in humans is important as zoonosis precludes the assumption that human immune system may be na€ıve to these vectors. Additionally, as impor- tant pathogens, adenoviruses are a model …

The Impact Of The Abuse-Deterrent Reformulation Of Extended-Release T Oxycontin On Prescription Pain Reliever Misuse And Heroin Initiation, Carolyn Wolff, William N. Dowd, Mir M. Ali, Chandler Mcclellan, Angelica Meinhofer, Lukas Glos, Ryan Mutter, Matthew Rosenberg, Andreas Schikc

United States Food and Drug Administration: Publications

The introduction of abuse-deterrent OxyContin in 2010 was intended to reduce its misuse by making it more tamper resistant. However, some studies have suggested that this reformulation might have had unintended consequences, such as increases in heroin-related deaths. We used the 2005–2014 cross-sectional U.S. National Survey on Drug Use and Health to explore the impact of this reformulation on intermediate outcomes that precede heroin-related deaths for individuals with a history of OxyContin misuse. Our study sample consisted of adults who misused any prescription pain reliever prior to the reformulation of OxyContin (n = 81,400). Those who misused OxyContin prior to …

Development Of A Nicotinic Acetylcholine Receptor Nachr Α7 Binding Activity Prediction Model, Sugunadevi Sakkiah, Carmine Leggett, Bohu Pan, Wenjing Guo, Luis G. Valerio Jr., Huixiao Hong

United States Food and Drug Administration: Publications

Despite the well-known adverse health effects associated with tobacco use, addiction to nicotine found in tobacco products causes difficulty in quitting among users. Nicotinic acetylcholine receptors (nAChRs) are the physiological targets of nicotine and facilitate addiction to tobacco products. The nAChR-α7 subtype plays an important role in addiction; therefore, predicting the binding activity of tobacco constituents to nAChR-α7 is an important component for assessing addictive potential of tobacco constituents. We developed an α7 binding activity prediction model based on a large training data set of 843 chemicals with human α7 binding activity data extracted from PubChem and ChEMBL. The model …

Long-Term Negative Emotional Outcomes Of Warzone Tbi, Jennifer J. Vasterling, Mihaela Aslan, Susan P. Proctor, John Ko, Xenia Leviyah, John Concato

United States Food and Drug Administration: Publications

Objective: Many veterans of the Iraq and Afghanistan Wars have experienced traumatic brain injury (TBI). Although prior work has examined associations between TBI and development of psychi- atric syndromes, less is known about associations between TBI and component emotions constituting these syndromes, especially in the long term. The purpose of this study was to examine the long-term emotional consequences of deployment-related TBI.

Methods: As part of VA Cooperative Studies Program #566, we assessed a sample of n1⁄4456US Army soldiers prior to an index deployment to Iraq, and again an average of 8.3 years (SD1⁄42.4years) after their deployment for a long-term …

Regulatory Malfunctions In The Drug Patent Ecosystem, Ana Santos Rutschman

All Faculty Scholarship

Patent protection for several of the world’s best-selling and most promising drugs — biologics — has begun waning. Over the next few years, many other drugs in this category will lose critical patent protection. In principle, this should open the United States market to competition, as more manufacturers are now able to produce relatively cheaper versions of these expensive drugs, known as biosimilars. That, however, has not been the case. This Article examines this problem in the context of the articulation between anticompetitive behaviors and regulatory interventions in the biopharmaceutical arena, and argues for a novel solution: a timelier response …

The Intellectual Property Of Vaccines: Takeaways From Recent Infectious Disease Outbreaks, Ana Santos Rutschman

All Faculty Scholarship

This Essay examines the ways in which intellectual property regimes influence incentives for the development of new vaccines for infectious diseases. Charting the tension between market forces and public health imperatives, the Essay considers an emerging solution to the long-standing problem of insufficient incentives for vaccine research and development: the rise of public-private partnerships in the health space. The Essay provides a short case study on CEPI, a large-scale public-private partnership dedicated exclusively to funding research on vaccines for infectious diseases. In exploring how the interaction between intellectual property rules and practices affect vaccine innovation, the Essay offers illustrations from …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.

First, we generated a novel transgenic animal using the epithelial-specific …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

The Comparative Efficacy Of Amantadine Vs. Lcig Therapy For The Treatment Of Levodopa-Induced Dyskinesia In Patients With Advanced Parkinson's Disease, Katelynn Timony

Capstone Showcase

Introduction: Though levodopa-carbidopa therapy remains the gold standard of Parkinson’s disease (PD) treatment to this day, patients often experience increased dyskinetic activity as a result of long-term treatment; known as levodopa-induced dyskinesia (LID); the mechanism of which is not completely understood. In this review, the efficacy of two adjunct treatments for LID are compared: 1) the concomitant administration of amantadine, an antiviral medication with antidyskinetic properties; and 2) a new form of levodopa administration in the form of an intestinal gel delivered straight via a device much like an insulin pump.

Methods: Two systematic literature searches of primary, peer-reviewed articles …

Naming Convention, Interchangeability, And Patient Interest In Biosimilars, Mariana P. Socal, Jace B. Garrett, William B. Tayler, Ge Bai, Gerard F. Anderson

Faculty Publications

Although biosimilars may offer cost savings over their comparable biologics, use of biosimilars in the United States remains relatively low. This study investigates two barriers to uptake of biosimilars in the United States. First, the U.S. Food and Drug Administration requires that four-letter suffixes be added to the nonproprietary names of all biosimilars, as well as to the nonproprietary names of all biologics approved after March 2020. Second, biosimilars are not interchangeable with their reference biologic product at the pharmacy counter; a new prescription is needed for the biosimilar to be dispensed in place of the biologic. We conducted two …

Pharmaceutical Manufacturing In The 21st Century: Identification And Analysis Of Key Elements, Robert N. Mills

Honors Program: Senior Projects (Public)

The availability of quality pharmaceutical products impacts the lives of the global population on a daily basis. The importance of product availability and quality within pharmaceutical manufacturing requires that quality systems put into place are capable of accurately and robustly capturing the quality compliance, or lack thereof, of the various stages of production. This review intends to analyze current expert-recommended best practices within key elements of a pharmaceutical manufacturing quality control system and provide recommendations throughout. The quality elements discussed include Quality by Design method validation, necessary equipment determination, and equipment qualification, followed by documentation control and data flow.

Molecular And Behavioral Mechanisms Mediated Paclitaxel-Induced Changes In Affect-Like Behavior In Mice, Julia Meade

Theses and Dissertations

Paclitaxel and oxaliplatin are two chemotherapeutics that cause acute neurotoxicity and chemotherapy-induce peripheral neuropathy (CIPN) in 70-90% of cancer patients. Chemotherapy-induced sensory changes are correlated with depression and anxiety. We characterized the effects of these drugs on sensation and various mood-related behaviors in mice, to determine if changes in sensation are associated with depression-like behavior, to explore putative mechanisms of chemotherapy-induced depression-like behavior (Aim 1), and to develop a mouse model of chemotherapy-induced operant responding deficit (Aim 2). In Aim 1, we observed that a cumulative dose of 32 mg/kg paclitaxel induced mechanical hypersensitivity and transiently reduced preference for sucrose …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Chlorhexidine Gluconate Vs Povidone-Iodine In The Prevention Of Clean-Contaminated Surgical Site Infections, Erin Layne, Abigail Stone

Physician Assistant Capstones, 2016 to 2019

Abstract

Background:

A patient’s skin is the major source of pathogens that can cause post-operative complications such as surgical site infections (SSIs). Optimization of pre-operative skin antisepsis is obtained with chlorhexidine gluconate (CG) and povidone-iodine (PI). These two solutions are the most widely used antiseptics for pre-operative purposes.

Objective:

Among surgical patients greater than 18 years of age undergoing clean-contaminated surgery, which antiseptic, iodophors or chlorhexidine gluconate, is more effective at reducing postoperative surgical site infections?

Methods:

A search was done in PubMed utilizing the terms chlorhexidine, infection control, iodophors, and surgical site infection. The limits applied included randomized …