Pharmacy and Pharmaceutical Sciences Commons^™

Potential Roles Of Endoplasmic Reticulum Stress And Cellular Proteins Implicated In Diabesity, Sagir Mustapha, Mustapha Mohammed, Ahmad Khusairi Azemi, Ismaeel Yunusa, Aishatu Shehu, Lukman Mustapha, Yusuf Wada, Mubarak Hussaini Ahmad, Wan Amir Wan Ahmad, Aida Hanum Ghulam Rasool, Siti Safiah Mokhtar

Faculty Publications

The role of the endoplasmic reticulum (ER) has evolved from protein synthesis, processing, and other secretory pathways to forming a foundation for lipid biosynthesis and other metabolic functions. Maintaining ER homeostasis is essential for normal cellular function and survival. An imbalance in the ER implied stressful conditions such as metabolic distress, which activates a protective process called unfolded protein response (UPR). This response is activated through some canonical branches of ER stress, i.e., the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6). Therefore, chronic hyperglycemia, hyperinsulinemia, increased proinflammatory …

Impact Of Follow Up Blood Cultures On Outcomes Of Patients With Community-Onset Gram-Negative Bloodstream Infection, Rajiv Amipara, Hana Rac Winders, Julie Ann Justo, P Brandon Bookstaver, Joseph Kohn, Majdi N. Al-Hasan

Faculty Publications

Background: The role of follow up blood cultures (FUBC) in the management of gram-negative bloodstream infection (GN-BSI) remains controversial. This retrospective cohort study examines the association between obtaining FUBC and mortality in GN-BSI.

Methods: Hospitalized adults with community-onset GN-BSI at Prisma Health-Midlands hospitals in South Carolina, USA from January 1, 2010 to June 30, 2015 were identified. Patients who died or were discharged from hospital within 72 h were excluded to minimize impact of survival and selection biases on results, respectively. Multivariate Cox proportional hazards regression was used to examine association between obtaining FUBC and 28-day all-cause mortality after adjustment …

Public Opinion Regarding Government Response To Covid-19: Case Study Of A Large Commercial City In Nigeria, Ismaeel Yunusa Ph.D., Sorochi Iloanusi, Osaro Mgbere, Nchebe-Jah Raymond Iloanusi, Anthony Idowu Ajayi, Ekere James Essien

Faculty Publications

Introduction: government measures to contain the COVID-19 pandemic cannot be effective without widespread compliance by the public. A greater understanding of citizens' perceptions of these measures can help government agencies adapt their strategies to boost compliance. We examined citizens' perceptions of government's measures to contain the COVID-19 pandemic and its implications on compliance using data from Onitsha city, Anambra State Nigeria.

Methods: data was obtained through in-person interviews of 140 consenting adults in March 2020. Descriptive and inferential statistics were used to summarize the data.

Results: most participants (84.7%) doubted government's ability to manage the COVID-19 outbreak, raising concerns about …

Hearing Loss Prevalence And Years Lived With Disability, 1990–2019: Findings From The Global Burden Of Disease Study 2019, Ismaeel Yunusa, Lydia M. Haile, Kaloyan Kamenov, Paul Svitil Briant, Aislyn U. Orji, Jaimie D. Steinmetz, Et. Al.

Faculty Publications

Background

Hearing loss affects access to spoken language, which can affect cognition and development, and can negatively affect social wellbeing. We present updated estimates from the Global Burden of Disease (GBD) study on the prevalence of hearing loss in 2019, as well as the condition's associated disability.

Methods

We did systematic reviews of population-representative surveys on hearing loss prevalence from 1990 to 2019. We fitted nested meta-regression models for severity-specific prevalence, accounting for hearing aid coverage, cause, and the presence of tinnitus. We also forecasted the prevalence of hearing loss until 2050.

Findings

An estimated 1.57 billion (95% uncertainty interval …

Application Of Standardized Antimicrobial Administration Ratio As A Motivational Tool Within A Multi-Hospital Healthcare System, Stephanie Shealy, Joseph Kohn, Emily Yongue, Casey Troficanto, P Brandon Bookstaver, Julie Ann Justo, Hana R. Winders, Sangita Dash, Majdi N. Al-Hasan

Faculty Publications

The standardized antimicrobial administration ratio (SAAR) is a novel antimicrobial stewardship metric that compares actual to expected antimicrobial use (AU). This prospective cohort study examines the utility of SAAR reporting and inter-facility comparisons as a motivational tool to improve overall and broad-spectrum AU within a three-hospital healthcare system. Transparent inter-facility comparisons were deployed during system-wide antimicrobial stewardship meetings beginning in October 2017. Stakeholders were advised to interpret the results to foster competition and incorporate SAAR data into focused antimicrobial stewardship interventions. Student's -test was used to compare mean SAARs in the pre- (July 2017 through October 2017) and post-intervention periods …

The Inhibition Of Cdk8/19 Mediator Kinases Prevents The Development Of Resistance To Egfr-Targeting Drugs, Amanda C. Sharko, Chang-Uk Lim, Martina S.J. Mcdermott, Chuck Hennes, Kingsavanh P. Philavong, Tiffanie Aiken, Victor V. Tatarskiy, Igor Roninson Ph. D., Eugenia Broude

Faculty Publications

Drug resistance is the main obstacle to achieving cures with both conventional and targeted anticancer drugs. The emergence of acquired drug resistance is initially mediated by non-genetic transcriptional changes, which occur at a much higher frequency than mutations and may involve population-scale transcriptomic adaptation. CDK8/19 kinases, through association with transcriptional Mediator complex, regulate transcriptional reprogramming by co-operating with different signal-responsive transcription factors. Here we tested if CDK8/19 inhibition could prevent adaptation to drugs acting on epidermal growth factor receptor (EGFR/ERBB1/HER1). The development of resistance was analyzed following long-term exposure of BT474 and SKBR3 breast cancer cells to EGFR-targeting small molecules …

Less Common Bacterial, Fungal And Viral Infections: Review Of Management In The Pregnant Patient, Alyssa P. Gould, Hana R. Winders, Kayla R. Stover, P Brandon Bookstaver, Brooke Griffin, Christopher M. Bland, Lea S. Eiland, Milena Murray

Faculty Publications

This review is a comprehensive summary of treatment options for pregnant patients with less common bacterial, fungal, and viral infections. It offers guidance to clinicians based on the most recently published evidence-based research and expert recommendations. A search of MEDLINE (inception to March 2021) and the CDC website was performed. Liposomal amphotericin B is the preferred therapy for cryptococcosis, histoplasmosis, oesophageal candidiasis, and coccidioidomycosis, especially during the first trimester due to teratogenic concerns with azole antifungals. For oral candidiasis, clotrimazole troches or miconazole mucoadhesive buccal tablets are recommended. A β-lactam antimicrobial is preferred over doxycycline for various manifestations of Lyme …

Consequences To Patients, Clinicians, And Manufacturers When Very Serious Adverse Drug Reactions Are Identified (1997-2019): A Qualitative Analysis From The Southern Network On Adverse Reactions (Sonar), Charles L. Bennett M.D., Ph.D., Shamia Hoque, Nancy Olivieri, Matthew A. Taylor, David Aboulafia, Courtney Lubaczewski, Andrew C. Bennett, Jay Vemula, Benjamin Schooley, Bartlett J. Witherspoon, Ashley C. Godwin, Paul S. Ray, Marc Fishman, Georgne Herring, Anne Ventrone, Juan Aldaco, William J. Hrushesky, John Restaino, Henrik S. Thomsen, Robert Marx, Et. Al.

Faculty Publications

Background

Methods

The Roles Of Osteopontin In The Pathogenesis Of West Nile Encephalitis, Farzana Nazneen, Fengwei Bai

Faculty Publications

Osteopontin (OPN), a multifunctional protein encoded by the secreted phosphoprotein-1 (Spp-1) gene in humans, plays important roles in a variety of physiological conditions, such as biomineralization, bone remodeling and immune functions. OPN also has significant roles in the pathogenesis of autoimmune, allergy and inflammatory diseases, as well as bacterial, fungal and viral infections. West Nile virus (WNV), a mosquito-transmitted flavivirus, is the leading agent for viral encephalitis in North America. Recent progress has been made in understanding both the biological functions of OPN and the pathogenesis of WNV. In this review article, we have summarized the current understanding of the …

A Baker's Dozen Of Top Antimicrobial Stewardship Intervention Publications In 2019, Kayla R. Stover, Elias B. Chahine, David Cluck, Sarah Green, Daniel B. Chastain, Darrell Childress, Carmen Faulkner-Fennell, Katherine Lusardi, Edoabasi U. Mcgee, Michelle Turner, P Brandon Bookstaver, Christopher M. Bland

Faculty Publications

Staying current on literature related to antimicrobial stewardship can be challenging given the ever-increasing number of published articles. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an actionable intervention for 2019. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training and to identify potential intervention opportunities within one's institution.

Redox-Sensitive Nanocomplex For Targeted Delivery Of Melittin, Bei Cheng, Peisheng Xu

Faculty Publications

Although peptide therapeutics have been explored for decades, the successful delivery of potent peptides in vitro and in vivo remains challenging due to the poor stability, low cell permeability, and off-target effects. We developed a redox sensitive polymer-based nanocomplex which can efficiently and stably deliver the peptide drug melittin for cancer therapy. The nanocomplex selectively targets cancer cells through lactobionic acid mediated endocytosis and releases melittin intracellularly upon the trigger of elevated redox potential. In vivo study proved that the targeted nanocomplex shows excellent potency in inhibiting tumor growth in a xenograft colon cancer mouse model. Thus, the polymer/melittin nanocomplexes …

Empirical Fluoroquinolones Versus Broad-Spectrum Beta-Lactams For Gram-Negative Bloodstream Infections In The Absence Of Antimicrobial Resistance Risk Factors, Majdi N. Al-Hasan, Alyssa P. Gould, Chelsea Drennan, Olivia Hill, Julie Ann Justo, Joseph Kohn, P Brandon Bookstaver

Faculty Publications

OBJECTIVES: Increasing antimicrobial resistance rates limit empirical antimicrobial treatment options for Gram-negative bloodstream infections (GN-BSI). However, antimicrobial resistance may be predicted based on patient-specific risk factors using precision medicine concepts. This retrospective, 1:2 matched cohort examined clinical outcomes in hospitalized adults without major risk factors for antimicrobial resistance receiving empirical fluoroquinolones or broad-spectrum beta-lactams (BSBL) for GN-BSI at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 2010 through June 2015. METHODS: Multivariable logistic regression was used to examine early treatment failure at 72-96 h from GN-BSI. Cox proportional hazards regression was used to examine 28-day mortality and hospital length …

The Mbeya Antimicrobial Stewardship Team: Implementing Antimicrobial Stewardship At A Zonal-Level Hospital In Southern Tanzania, Jeffrey W. Hall, Jeannette Bouchard, P Brandon Bookstaver, Matthew S. Haldeman, Peter Kishimbo, Godlove Mbwanji, Issakwisa Mwakyula, Davance Mwasomola, Megan Seddon, Mark Shaffer, Stephanie C. Shealy, Anthony Nsojo

Faculty Publications

In 2017, Mbeya Zonal Referral Hospital (MZRH) and the University of South Carolina (UofSC) agreed to collaboratively strengthen antimicrobial prescribing in the southern highlands of Tanzania and train a new generation of clinicians in responsible antimicrobial use. Key stakeholders and participants were identified and the Mbeya Antimicrobial Stewardship Team (MAST) was created. The team identified assets brought by the collaborators, and four investigations of baseline needs were developed. These investigations included (a) a baseline clinician survey regarding antimicrobial resistance and stewardship, (b) a serial chart review of inpatient antimicrobial prescribing practices, (c) an investigation of antimicrobial resistance rates using existing …

The Association Between Phosphodiesterase-5 Inhibitors And Colorectal Cancer In A National Cohort Of Patients, S. Scott Sutton, Joseph Magagnoli, Tammy H. Cummings, James W. Hardin

Faculty Publications

INTRODUCTION: To examine the association between phosphodiesterase-5 (PDE-5) inhibitor use and incidence of colorectal cancer among patients with erectile dysfunction treated in the Veterans Affairs (VA) Healthcare System. METHODS: A retrospective cohort study using the Veterans Affairs Informatics and Computing Infrastructure was conducted, with data spanning January 2001-December 2016. Patients were followed up from index until (i) the first diagnosis of colorectal cancer, (ii) death, or (iii) the end of study period. Statistical analyses evaluated demographics and baseline characteristics between cohorts (PDE-5 exposed or not) and the effect of additional dosages of each specific PDE-5 inhibitor using adjusted multivariate Cox …

Prediction Of Trimethoprim/Sulfamethoxazole Resistance In Community-Onset Urinary Tract Infections, Madeline Demarsh, P Brandon Bookstaver, Caroline Gordon, Juanne Lim, Nicole Griffith, Nicole K. Bookstaver, Julie Ann Justo, Joseph Kohn, Majdi N. Al-Hasan

Faculty Publications

OBJECTIVES: This study aimed to predict trimethoprim/sulfamethoxazole (SXT) resistance in patients with community-onset urinary tract infection (UTI) due to Enterobacteriaceae based on patient-specific risk factors. METHODS: This was a retrospective case-control study in Prisma Health facilities in central South Carolina, USA, including three community hospitals, affiliated emergency departments and ambulatory clinics, including adult patients with community-onset UTI due to Enterobacteriaceae (1 April 2015 to 29 February 2016). Multivariate logistic regression was used to examine risk factors for SXT resistance. RESULTS: Among 351 unique patients with community-onset UTI, 71 (20.2%) had SXT-resistant Enterobacteriaceae urinary isolates. Overall, median age was 64 years …

Recent Advances In Stimuli-Responsive Drug Release And Targeting Concepts Using Mesoporous Silica Nanoparticles, Ghada G. Abdo, Moustafa M. Zagho, Ashraf Khalil

Faculty Publications

Being a developed and promising approach, nanotechnology has attracted a lot of attention in biomedical and pharmaceutical therapy applications. Among nanostructured materials, mesoporous silica nanoparticles (MSNs) are effectively used as nanocarriers for drug delivery systems. MSNs can be tailored-designed by different synthetic techniques. Their morphological characteristics dictate the type of application of such materials. Recently, polymer-based materials have been employed to functionalize the MSNs surface. These modified nanocarriers are loaded with the drug and can unload their “cargo” upon exposure to either endogenous or exogenous types of stimuli. In this study, different targeting concepts, including passive, active, vascular, nuclear, and …

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy For Bloodstream Infections Secondary To Enterobacter, Serratia, And Citrobacter Species, Caroline Derrick, P. Brandon Bookstaver, Zhiqiang K. Lu, Christopher M. Bland, S. Travis King, Kayla R. Stover, Kathey Rumley, Shawn H. Macvane, Jenna Swindler, Scott Kincaid, Trisha Branan, David Cluck, Benjamin Britt, Kelly E. Pillinger, Bruce M. Jones, Virginia Fleming, V. Paul Dimondi, Sandy Estrada, Brad Crane, Brian Odle, Majdi N. Al-Hasan, Julie Ann Justo

Faculty Publications

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of …

Pharmacist-Driven Culture And Sexually Transmitted Infection Testing Follow-Up Program In The Emergency Department, Stephanie C. Shealy, Christine Alexander, Tina Grof Hardison, Joseph Magagnoli, Julie Ann Justo, Caroline Derrick, Joseph Kohn, Hana Rac Winders, Troy Privette, Majdi N. Al-Hasan, P. Brandon Bookstaver

Faculty Publications

Expanding pharmacist-driven antimicrobial stewardship efforts in the emergency department (ED) can improve antibiotic management for both admitted and discharged patients. We piloted a pharmacist-driven culture and rapid diagnostic technology (RDT) follow-up program in patients discharged from the ED. This was a single-center, pre- and post-implementation, cohort study examining the impact of a pharmacist-driven culture/RDT follow-up program in the ED. Adult patients discharged from the ED with subsequent positive cultures and/or RDT during the pre- (21 August 2018–18 November 2018) and post-implementation (19 November 2018–15 February 2019) periods were screened for inclusion. The primary endpoints were time from ED discharge to …

Impact Of Reappraisal Of Fluoroquinolone Minimum Inhibitory Concentration Susceptibility Breakpoints In Gram-Negative Bloodstream Isolates, Stephanie C. Shealy, Matthew M. Brigmon, Julie Ann Justo, P Brandon Bookstaver, Joseph Kohn, Majdi N. Al-Hasan

Faculty Publications

The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk factors for antimicrobial resistance. Gram-negative bloodstream isolates collected from hospitalized adults at Prisma Health-Midlands hospitals in South Carolina, USA, from January 2010 to December 2014 were included. Matched pairs mean difference (MD) with 95% confidence intervals (CI) were calculated to examine the change in ciprofloxacin susceptibility after MIC breakpoint reappraisal. Susceptibility of to ciprofloxacin declined by 5.2% (95% …

Evaluating Appropriateness And Diagnostic Stewardship Opportunities Of Multiplex Polymerase Chain Reaction Gastrointestinal Testing Within A Hospital System, Melissa O'Neal, Hanna Murray, Sangita Dash, Majdi N. Al-Hasan, Julie Ann Justo, P Brandon Bookstaver

Faculty Publications

Objective: This single-center, retrospective, observational cohort study evaluates the appropriateness of the BioFire® FilmArray® Gastrointestinal (GI) multiplex PCR panel testing at a community-teaching hospital. Methods: All adult, hospitalized patients at Prisma Health Richland Hospital with a documented GI multiplex PCR panel from 1 April 2015 through 28 February 2018 were included in the analysis. Inappropriate use of the GI panel was defined as a test obtained without documented diarrhea, greater than 2 days of hospitalization, redundant use with other diagnostic tests (e.g. PCR), or laxative use in the preceding 48 h. Antibiotic use and host variables were compared between groups …

Online Availability Of Fish Antibiotics And Documented Intent For Self-Medication, Weiwei Zhang, Austin Williams, Nicole Griffith, Jessica Gaskins, P Brandon Bookstaver

Faculty Publications

Self-medication and antibiotic utilization without healthcare oversight may lead to delayed appropriate treatment, transmission of communicable infections, untoward adverse events, and contribute to antimicrobial resistance. Previous data suggest people obtain over-the-counter (OTC) animal antibiotics for their personal use. This study examined the availability of OTC fish antibiotics online and the documented intent for self-medication. The authors conducted a web-based cross-sectional study using Google search engine to identify vendor websites selling fish antibiotics in the United States. Vendor websites were included if product information, consumer reviews, and comments were publicly available. Nine fish antibiotics were chosen due to their possibility of …

Healthcare Practitioners’ Views Of Social Media As An Educational Resource, Adam G. Pizzuti, Karan H. Patel, Erin K. Mccreary, Emily Heil, Christopher M. Bland, Eric Chinaeke, Bryan L. Love, P Brandon Bookstaver

Faculty Publications

Social media is increasingly utilized as a resource in healthcare. We sought to identify perceptions of using social media as an educational tool among healthcare practitioners. An electronic survey was distributed to healthcare administrators, nurses, nurse practitioners, pharmacists, physicians, and physician assistants f hospital systems and affiliated health science schools in Georgia, Maryland, South Carolina, and Wisconsin. Survey questions evaluated respondents' use and views of social media for educational purposes and workplace accessibility using a Likert scale (1 = strongly disagree, 5 = strongly agree). Nurses (75%), pharmacists (11%), and administrators (7%) were the most frequent respondents. Facebook® (27%), Pinterest® …

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 …

Systemic Toxicity Reported For Cdk8/19 Inhibitors Cct251921 And Msc2530818 Is Not Due To Target Inhibition, Mengqian Chen, Jing Li, Jiaxin Liang, Zanshé S. Thompson, Katie Kathrein, Eugenia Broude, Igor Roninson

Faculty Publications

CDK8/19 kinases, which mediate transcriptional reprogramming, have become an active target for cancer drug discovery. Several small-molecule CDK8/19 inhibitors showed in vivo efficacy and two have entered clinical trials, with no significant toxicities reported. However, Clarke et al. (eLife 2016; 5; e20722) found severe systemic toxicity associated with two potent CDK8/19 inhibitors, Cmpd3 (CCT251921) and Cmpd4 (MSC2530818), and suggested that their toxicity was due to on-target effects. Here, we compared five CDK8/19 inhibitors: Cmpd3, Cmpd4, Senexin B, 16-didehydro-cortistatin A (dCA) and 15w, in different assays. Only Cmpd4 showed striking toxicity in developing zebrafish. In cell-based assays for CDK8 and CDK19 …

A Baker's Dozen Of Top Antimicrobial Stewardship Intervention Publications In 2018, Elias B. Chahine, Spencer H. Durham, Krutika N. Mediwala, Daniel B. Chastain, Timothy P. Gauthier, Brandon K. Hill, Bruce M. Jones, Jamie J. Kisgen, Ashley H. Marx, Kayla R. Stover, Marylee V. Worley, Christopher M. Bland, P Brandon Bookstaver

Faculty Publications

With an increasing number of antimicrobial stewardship-related articles published each year, attempting to stay current is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an actionable intervention for 2018. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training as well as to identify potential intervention opportunities within one's institution.

Characterizing Cdk8/19 Inhibitors Through A Nfκb-Dependent Cell-Based Assay, Jng Li, Donald C. Porter, Eugenia Broude, Igor Roninson, Mengqian Chen

Faculty Publications

Cell-based assays for CDK8/19 inhibition are not easily defined, since there are no known cellular functions unique to these kinases. To solve this problem, we generated derivatives of 293 cells with CRISPR knockout of one or both of CDK8 and CDK19. Double knockout (dKO) of CDK8 and CDK19 together (but not individually) decreased the induction of transcription by NFκB (a CDK8/19-potentiated transcription factor) and abrogated the effect of CDK8/19 inhibitors on such induction. We generated wild type (WT) and dKO cell lines expressing luciferase from an NFκB-dependent promoter. Inhibitors selective for CDK8/19 over other CDKs decreased TNFα-induced luciferase expression in …

Penicillin Allergy Assessment And Skin Testing In The Outpatient Setting, Wesley D. Kufel, Julie Ann Justo, P. Brandon Bookstaver, Lisa M. Avery

Faculty Publications

Penicillin allergies are among of the most commonly reported allergies, yet only 10% of these patients are truly allergic. This leads to potential inadvertent negative consequences for patients and makes treatment decisions challenging for clinicians. Thus, allergy assessment and penicillin skin testing (PST) are important management strategies to reconcile and clarify labeled penicillin allergies. While PST is more common in the inpatient setting where the results will immediately impact antibiotic management, this process is becoming of increasing importance in the outpatient setting. PST in the outpatient setting allows clinicians to proactively de-label and educate patients accordingly so beta-lactam antibiotics may …

Direct Measurement Of Performance: A New Era In Antimicrobial Stewardship, Majdi N. Al-Hasan, Hana Rac Winders, P. Brandon Bookstaver, Julie Ann Justo

Faculty Publications

Penicillin allergies are among of the most commonly reported allergies, yet only 10% of these patients are truly allergic. This leads to potential inadvertent negative consequences for patients and makes treatment decisions challenging for clinicians. Thus, allergy assessment and penicillin skin testing (PST) are important management strategies to reconcile and clarify labeled penicillin allergies. While PST is more common in the inpatient setting where the results will immediately impact antibiotic management, this process is becoming of increasing importance in the outpatient setting. PST in the outpatient setting allows clinicians to proactively de-label and educate patients accordingly so beta-lactam antibiotics may …

Penicillin Allergy Skin Testing In The Inpatient Setting, Julie Ann Justo, Wesley D. Kufel, Lisa Avery, P. Brandon Bookstaver

Faculty Publications

The consequences of a documented penicillin allergy in the medical record are especially troublesome in acutely ill, hospitalized patients. A penicillin allergy label may lead to alternative or second line therapies resulting in adverse drug events, negative clinical outcomes and increased costs. Reconciling penicillin allergies is a necessity to facilitate early, optimal therapy and is a shared responsibility among the healthcare team. Penicillin skin testing (PST) has been utilized successfully in hospitalized patients to de-label erroneous penicillin allergies and optimize antibiotic therapy. This targeted review aims to discuss the practical development and implementation of PST in the inpatient setting. This …

Identifying Cancers For Cdk8/19 Inhibitor Therapy, Igor Roninson, Balázs Győrffy, Zachary T. Mack, Alexander A. Shtil, Michael S. Shtutman, Mengqian Chen, Eugenia Broude

Faculty Publications

CDK8 and CDK19 Mediator kinases are transcriptional co-regulators implicated in several types of cancer. Small-molecule CDK8/19 inhibitors have recently entered or are entering clinical trials, starting with breast cancer and acute myeloid leukemia (AML). To identify other cancers where these novel drugs may provide benefit, we queried genomic and transcriptomic databases for potential impact of CDK8, CDK19, or their binding partner CCNC. sgRNA analysis of a panel of tumor cell lines showed that most tumor types represented in the panel, except for some central nervous system tumors, were not dependent on these genes. In contrast, analysis of clinical samples for …