Pharmacy and Pharmaceutical Sciences Commons^™

Association Between Cholinesterase Inhibitor-Overactive Bladder Antimuscarinic Prescribing Cascade And Risk Of Delirium And Falls Among Individuals Living With Dementia, Sarah Beth Tucker, Bryan L. Love Pharm D., Chijoke M. Okeke, Erin D. Zwick, Chengwen Teng Pharm.D., Ph.D., Jingkai Wei, Ibraheem M. Karaye, Saud Alsahali, Krithika Rajagopalan, Ismaeel Yunusa Ph.D.

Faculty Publications

Background

Prescribing cascades occur when cholinesterase inhibitor (ChEI)-induced urinary incontinence is misinterpreted as a new condition, leading to overactive bladder (OAB) antimuscarinic initiation. We evaluated whether the ChEI-OAB antimuscarinic prescribing cascade was associated with delirium or falls compared with mirabegron in older adults living with dementia.

Methods

We conducted a retrospective cohort study using the Anlitiks All-Payor Claims database (2015–2020). Participants were adults aged ≥ 65 years with dementia newly prescribed a ChEI with no prior ChEI or OAB therapy (180 days). A 60-day window identified OAB treatment initiation after ChEI therapy. Exposures were OAB antimuscarinics or mirabegron. Outcomes were …

Real-World Comparison Of Intravenous Vs. Oral Antimicrobial Therapy For Bone And Joint Infections, Maura Kreiser, Sarah Al Mansi, Ismaeel Yunusa Ph.D., Caroline Derrick, P. Brandon Bookstaver Pharm.D., Majdi N. Al-Hasan, Yorika Hammett, Morgan Pizzuti

Faculty Publications

Well-designed randomized controlled trials (RCTs) have demonstrated safe and effective use of oral antimicrobial therapy for bone and joint infections. Application of data for implementation into real-world practice, however, has inherent challenges. This retrospective cohort study compared real-world use of intravenous versus oral antimicrobial therapy in bone and joint infections within a large healthcare system comprising both academic and community medical centers. The primary outcome was the proportion of treatment failure. Key secondary outcomes included the proportion of patients with logistical failure and risk factors associated with treatment and logistical failure. Among 166 patients included, 136 (82%) and 30 (18%) …

Cost-Effectiveness Of Pregabalin, Duloxetine, And Milnacipran Vs Amitriptyline For Moderate To Severe Fibromyalgia, Sarah S. Downen, Hussein M. Farag, Abby Davis, Chijioke M. Okeke, Kenechukwu C. Ben-Umeh, Ismaeel Yunusa Ph.D., Tewodros Eguale

Faculty Publications

Importance

Fibromyalgia (FM) is a chronic pain condition associated with substantial quality-of-life impairments and economic burden. Although multiple pharmacologic options are recommended in clinical guidelines, the relative cost-effectiveness of off-label amitriptyline compared with FDA-approved treatments remains poorly defined due to a scarcity of direct economic comparisons and the use of heterogenous outcome measures in the extant literature.

Objective

To evaluate the cost-effectiveness of pregabalin, duloxetine, and milnacipran compared with amitriptyline in adults with moderate to severe FM.

Design, Setting, and Participants

Decision analytical model using a Markov cohort state transition model to estimate lifetime costs and quality-adjusted life-years (QALYs) for …

Host-Derived Interleukin-1Α Drives Tumor Immunosuppression By Reprogramming Tumor-Associated Myeloid Cells, Manikanda Raja Keerthi Raja, Gourab Gupta, Grace Atkinson, Katie Kathrein, Alissa R. Armstrong, R. Michael Gower, Igor Roninson Ph.D., Eugenia Broude, Mengqian Chen Ph.D., Hao Ji, Chang-Uk Lim, Hongjun Wang, Daping Fan, Peisheng Xu Ph.D., Hexin Chen

Faculty Publications

Myeloid cells are highly heterogeneous and play key roles in establishing an immunosuppressive tumor microenvironment (TME), but the mechanisms controlling their differentiation remain unclear. Using orthotopic murine breast cancer models, we investigated how interleukin-1α (IL-1α) influences this process. Deletion of host Il1α resulted in rejection of transplanted tumors. Single-cell RNA sequencing identified CX3CR1⁺ macrophages as the main source of IL-1α in the TME. Il1α deficiency disrupted monocyte–macrophage differentiation, reducing CX3CR1⁺ macrophages and increasing iNOS⁺ macrophages. Myeloid cells from Il1α⁻/⁻ hosts induced lower PD-1 and CTLA-4 expression in co-cultured CD8⁺ T cells than those from wild-type hosts. CellChat analysis showed …

Anoikis Resistance And Metastasis Of Ovarian Cancer Can Be Overcome By Cdk8/19 Mediator Kinase Inhibition, Mehri Monavarian, Resha Rajkarnikar, Emily Faith Page, Asha Kumari, Liz Quintero Macias, Felipe Massicano, Nam. Y. Lee, Sarthak Sahoo, Nadine Hempel, Mohit Kumar Jolly, Lara Ianov, Elizabeth Worthey, Abhyudai Singh, Igor Roninson Ph.D., Eugenia Broude Ph.D., Mengqian Chen Ph.D., Karthikeyan Mythreye

Faculty Publications

Anoikis resistance, or evasion of cell death triggered by matrix detachment, is a hallmark of cancer cell survival and metastasis. We showed that repeated exposure to suspension stress followed by recovery under attached conditions leads to development of anoikis resistance. The acquisition of anoikis resistance was associated with enhanced invasion, chemoresistance, and immune evasion in vitro and distant metastasis in vivo. This acquired anoikis resistance was not genetic, persisting for a finite duration without detachment stress, but was sensitive to CDK8/19 mediator kinase inhibition that could also reverse anoikis resistance. Transcriptomic analysis revealed that CDK8/19 kinase inhibition induces bidirectional transcriptional …

Molecular Survival Strategies Against Kidney Filtration: Implications For Therapeutic Protein Engineering, William Heaps, Anna Elise Packard, Kristina M. Mccammon, Tyler P. Green, Joseph P. Talley, Bradley C. Bundy, Dennis Della Corte

Faculty Publications

The glomerular filtration barrier poses a significant challenge for circulating proteins, with molecules below ~60–70 kDa facing rapid renal clearance. Endogenous proteins have evolved sophisticated evasion mechanisms including oligomerization, carrier binding, electrostatic repulsion, and FcRn-mediated recycling. Understanding these natural strategies provides blueprints for engineering therapeutic proteins with improved pharmacokinetics. This review examines how endogenous proteins resist filtration, evaluates their application in protein engineering, and discusses clinical translation including established technologies (PEGylation, Fc-fusion) and emerging strategies (albumin-binding domains, glycoengineering). We address critical challenges of balancing half-life extension with tissue penetration, biological activity, and immunogenicity—essential considerations for the rational design of next-generation …

Cdk8/19 Inhibition Attenuates G1 Arrest Induced By Bcr-Abl Arrest Induced By Bcr-Abl Antagonists And Accelerates Death Of Chronic Myelogenous Leukemia Cells, Alvina I. Khamidullina, Margarita A. Yastrebova, Alexandra V. Bruter, Julia V. Nuzhina, Nadezhda E. Vorobyeva, Anastasia M. Khrustaleva, Ekaterina A. Varlamova, Alexander V. Tyakht, Iaroslav E. Abramenko, Ekaterina S. Ivanova, Maria A. Zamkova, Jing Li, Chang-Uk Lim, Mengqian Chen, Eugenia V. Broude, Igor B. Roninson, Alexander A. Shtil, Victor V. Tatarskiy

Faculty Publications

Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (BCR-ABLi) are the mainstay of chronic myelogenous leukemia (CML) treatment. However, activation of circumventing signaling pathways and quiescence may limit BCR-ABLi efficacy. CDK8/19 Mediator kinases have been implicated in the emergence of non-genetic drug resistance. Dissecting the effects of pharmacological CDK8/19 inhibition on CML survival in response to BCR-ABLi, we found that a selective, non-toxic CDK8/19 inhibitor (CDK8/19i) Senexin B (SenB) and other CDK8/19i sensitized K562 cells to different BCR-ABLi via attenuation of cell cycle arrest. In particular, SenB prevented IM-induced upregulation of genes that negatively regulate cell cycle progression. SenB …

Local Injection Of Particles For Retinoic Acid Drug Delivery Improves Muscle Structure And Modulates Inflammation In Mice Recovering From Cast Immobilization, Candice V. Cheung, Regina A. Searcy, Kidochukwu J. Atube, Nicholas A. Colonna, Kelsey E. Krusen, Kate J. Cappage, Khufu M. Holly, R. Paul Ward Pratz, Jessie H. Fournier, Vitali Sikirzhytski Ph.D.

Faculty Publications

Disuse muscle atrophy secondary to acute illness or injury prolongs recovery and increases risk of permanent disability as a result of reduced muscle strength and myofiber damage upon reambulation. However, there are no pharmacotherapies to support muscle growth and repair following prolonged immobility. We propose that all-trans retinoic acid (ATRA) may support recovery of atrophied muscle via modulation of satellite cells and macrophages. Clinical application of ATRA is hindered by solubility, stability, and the need for high systemic doses. Therefore, in the current study, we developed poly(lactide-co-glycolide) (PLG) particles for local injection and extended release of ATRA (ATRA-PLG) and investigated …

Adipose Tissue Estrogen Receptor-Alpha Overexpression Ameliorates High-Fat Diet–Induced Adipose Tissue Inflammation, Marion C. Hope, Christian A. Unger, M. Chase Kettering, Cassidy E. Socia, Ahmed K. Aladhami, Barton C. Rice, Darya S. Niamira, Ben P. Wiznitzer, Diego Altomare Ph.D., William E. Cotham, Reilly T. Enos

Faculty Publications

Context

We created an innovative mouse model that enables inducible overexpression of estrogen receptor-alpha (ERα), specifically in adipose tissue (Adipo-ERα↑). Objective

We aimed to investigate how elevated Adipo-ERα↑ influences the development of high-fat diet (HFD)-induced obesity in both male and female mice. Methods

Male and female Adipo-ERα↑ mice and littermate controls were fed a low-fat diet (LFD) or HFD for 13 weeks. Adipo-ERα↑ was induced at the initiation of dietary treatment. Body morphology and composition, hepatic lipid accumulation, glucose tolerance, fasting insulin concentrations, and adipose tissue mRNA profiling were assessed. Liquid chromatography–mass spectrometry was used to determine circulating and adipose …

Cannabis Improves Metabolic Dysfunction And Macrophage Signatures In Obese Mice, Brandon N. Vanderveen, Thomas D. Cardaci, Christian A. Unger, Mitchell M. Nesmith, Jeffrey C. Freeman, Arianna V. Bastian, Kasie Roark, Mansi Upadhyay, Andrew G. Levy, Brooke M. Bullard, Sierra J. Mcdonald, Kandy T. Velázquez, Reilly T. Enos, Jason L. Kubinak, Lorne J. Hofseth Ph.D., James Hébert Scd, Daping Fan, E. Angela Murphy

Faculty Publications

Obesity rates continue to rise, highlighting the need for new treatments that are effective, safe, and widely accessible. Aligned with the easing of restrictions on cannabis use, interest in its therapeutic potential is evolving. As such, we examined the effects of the cannabis plant with high cannabidiol (CBD) content or high Δ9-tetrahydrocannabinol (THC) content on metabolic and immune dysregulation in obese mice. Briefly, female C57BL/6 mice were randomized into four groups (n = 15/group): 1) lean, 2) obese placebo, 3) obese CBD, and 4) obese THC. Lean mice consumed a low-fat diet for the study …

Adipose Tissue Estrogen Receptor-Alpha Overexpression Ameliorates High-Fat Diet–Induced Adipose Tissue Inflammation, Marion C. Hope, Christian A. Unger, M Chase Kettering, Cassidy E. Socia, Ahmed K. Aladhami, Barton C. Rice, Darya S. Niamira, Ben P. Wiznitzer, Diego Altomare Ph.D., William E. Cotham, Reilly T. Enos

Faculty Publications

Context

We created an innovative mouse model that enables inducible overexpression of estrogen receptor-alpha (ERα), specifically in adipose tissue (Adipo-ERα↑). Objective

We aimed to investigate how elevated Adipo-ERα↑ influences the development of high-fat diet (HFD)-induced obesity in both male and female mice. Methods

Male and female Adipo-ERα↑ mice and littermate controls were fed a low-fat diet (LFD) or HFD for 13 weeks. Adipo-ERα↑ was induced at the initiation of dietary treatment. Body morphology and composition, hepatic lipid accumulation, glucose tolerance, fasting insulin concentrations, and adipose tissue mRNA profiling were assessed. Liquid chromatography–mass spectrometry was used to determine circulating and adipose …

Diversity And Equity In Medical Education Over The Past Decade: Applications, Matriculations, And The Growing Gaps, Gang Lv, Xiangxiang Jiang, Jordan Franklin, Minghui Li, Jing Yuan, Z Kevin Lu Ph.D.

Faculty Publications

Background

Diversity and race-concordant relationships contribute to improved patient experiences and outcomes. In contrast, the representation of underrepresented in medicine (URiM) individuals in different medical specialties is declining. The essential pathway to improving diversity within the future workforce centers around the inclusion of a diverse cohort of medical students. We aimed to examine the diversity of medical school applications and admissions across sex, race and ethnicity over the past decade.

Methods

This study used data from the Association of American Medical Colleges from 2015 to 2024. URiM individuals refer to minority populations that are underrepresented in the medical profession, including …

Association Of Nucleoside Reverse Transcriptase Inhibitor Use With Reduced Risk Of Alzheimer's Disease Risk, Joseph Magagnoli Ph.D., Ms, Meenakshi Ambati, Tammy H. Cummings, Joseph Nguyen, Claire C. Thomas, Vidya L. Ambati, S. Scott Sutton, Bradley D. Gelfand, Jayakrishna Ambati

Faculty Publications

INTRODUCTION

Inflammasome activation is implicated in Alzheimer's disease (AD). We previously demonstrated that nucleoside reverse transcriptase inhibitors (NRTIs), drugs approved to treat human immunodeficiency virus (HIV) and hepatitis B, also inhibit inflammasome activation.

METHODS

We evaluated the association between NRTI exposure and subsequent development of AD in the United States Veterans Health Administration over a 24-year period and in the MarketScan database over a 14-year period using propensity score-matched multivariate Cox hazards regression and Kaplan–Meier analyses.

RESULTS

We report that in humans, NRTI exposure was associated with a significantly lower incidence of AD in two of the largest health insurance …

Cost-Effectiveness Analysis Of Aducanumab Versus Placebo For Patients With Mild Cognitive Impairment And Mild Alzheimer’S Disease, Xiaomo Xiong, Gang Lv, Jacob Jordan King, Minghui Li, Jing Yuan, Z Kevin Lu

Faculty Publications

Objectives To assess the cost-effectiveness of aducanumab at its updated price for treating patients with mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD).

Design Cost-effectiveness analysis.

Settings A five-state Markov model was constructed using 10 000 virtual patients to assess the cost-effectiveness of aducanumab from the perspective of the US healthcare system. The model employed a one-year cycle time and a lifetime time horizon. Transition probabilities and mortality rates were derived from a literature review. To address uncertainty and generalise the base case results, both one-way and probabilistic sensitivity analyses were conducted.

Participants 10 000 virtual patients with MCI …

Predicting Diabetes Self-Management Education Engagement: Machine Learning Algorithms And Models, Xiangxiang Jiang, Gang Lv, Minghui Li, Jing Yuan, Z Kevin Lu

Faculty Publications

Introduction Diabetes self-management education (DSME) is endorsed by the American Diabetes Association (ADA) as an essential component of diabetes management. However, the utilization of DSME remains limited in the USA. This study aimed to investigate current DSME participation among the older population and to identify comprehensive factors of DSME engagement through employing various machine learning (ML) models based on a US nationally representative survey linked to claims data.

Research design and methods Data from the Medicare Current Beneficiary Survey were employed, and this study included data on US Medicare beneficiaries with diabetes from 2017 to 2019. Comprehensive variables following the …

Appropriateness Of Ambulatory Antibiotic Prescribing In South Carolina, 2012–2017, Pamela Bailey, Majdi N. Al-Hasan, Julie Royer, Max Habicht, Julie Ann Justo, P. Brandon Bookstaver Pharm.D., Sharon Weissman, Hana R. Winders

Faculty Publications

This population-based cohort study examines the appropriateness of antibiotic prescribing in South Carolina via aggregated pharmacy claims data matched with diagnosis codes from medical claims. Inappropriate antibiotic prescribing decreased from 30.2% in 2012 to 22.6% in 2017 (P < 0.001) and was more common in adults >40 years old.

Mediator Kinase Inhibitors Suppress Triple-Negative Breast Cancer Growth And Extend Tumor Suppression By Mtor And Akt Inhibitors, Xiaokai Ding, Jiaxin Liang, Amanda C. Sharko, Thomas A. Hilimire, Jing Li, Jürgen Loskutov, Zachary T. Mack, Hao Ji, Gary P. Schools, Chao Cai, Elena N. Pugacheva, Mengqian Chen, Igor Roninson, Eugenia Broude

Faculty Publications

Triple-negative breast cancers (TNBC) are treated primarily by chemotherapy and lack clinically validated therapeutic targets. In particular, inhibitors of the PI3K/AKT/mTOR pathway, abnormally activated in many breast cancers, failed to achieve clinical efficacy in TNBC due to the development of adaptive drug resistance, which is largely driven by the transcriptomic plasticity of TNBC. Expression of CDK8/19 Mediator kinases that control transcriptional reprogramming correlates with relapse-free survival and treatment failure in breast cancer patients, including TNBC. We now investigated how CDK8/19 inhibitors affect the growth of TNBC tumors and their response to mTOR and AKT inhibitors. In contrast to the effects …

Allura Red Ac Is A Xenobiotic. Is It Also A Carcinogen?, Lorne J. Hofseth Ph.D., James Hébert Scd, Elizabeth Angela Murphy, Erica Trauner, Athul Vikas, Quinn Harris, Alexander A. Chumanevich

Faculty Publications

Merriam-Webster and Oxford define a xenobiotic as any substance foreign to living systems. Allura Red AC (a.k.a., E129; FD&C Red No. 40), a synthetic food dye extensively used in manufacturing ultra-processed foods and therefore highly prevalent in our food supply, falls under this category. The surge in synthetic food dye consumption during the 70s and 80s was followed by an epidemic of metabolic diseases and the emergence of early-onset colorectal cancer in the 1990s. This temporal association raises significant concerns, particularly given the widespread inclusion of synthetic food dyes in ultra-processed products, notably those marketed toward children. Given its interactions …

Removal Of Common Antimicrobial Agents By Sustained Low- Efficiency Dialysis, Joanna Q. Hudson Pharmd, Bcps, Fasn, Fccp, Madelyn N. Hilgers Bs, Pharmd Candidate, Elvira O. Gosmanova Md

Faculty Publications

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin–tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for …

The Prevalence Of Gram-Negative Bacteria With Difficult-To-Treat Resistance And Utilization Of Novel Β-Lactam Antibiotics In The Southeastern United States, Y. Vivian Tsai, P. Brandon Bookstaver Pharm.D., Joseph Kohn, Julie Ann Justo, Darrell Childress, Stefanie Stramel, Douglas Slain, Patrick Tu, Mary Joyce B. Wingler, Bruce M. Jones, Daniel T. Anderson, Megan M. Seddon, David A. Cretella, Joshua Eudy, Hana Winders, Kayla Antosz Pharm.D., Pamela Bailey, Majdi N. Al-Hasan

Faculty Publications

Objective:

To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel β-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design:

Retrospective, multicenter, cohort. Setting:

Ten hospitals in the southeastern United States. Methods:

GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel β-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) …

The Association Of Dietary Antioxidants And The Inflammatory Potential Of The Diet With Poor Physical Function And Disability In Older Australian Men: The Concord Health And Ageing In Men Project, Daniela Wizgier, Ying Meng, Arpita Das, Vasi Naganathan, Fiona Blyth, David G. Le Couteur, David J. Handelsman, Louise M. Waite, Rosilene V. Ribeiro, Nitin Shivappa, James Hébert Scd, Vasant Hirani

Faculty Publications

Our objective was to evaluate the association of antioxidant intake and the inflammatory potential of the diet with functional decline in older men. A diet history questionnaire was used to collect dietary intake data from men aged ≥ 75 years (n 794) participating in the Concord Health and Aging in Men Project cohort study. Intake of vitamins A, C, E and Zn were compared with the Australian Nutrient Reference Values to determine adequacy. The Energy-adjusted Dietary Inflammatory Index (E-DIITM) was used to assess the inflammatory potential of the diet. Physical performance data were collected via handgrip strength and walking speed …

A Baker’S Dozen Of Top Antimicrobial Stewardship Intervention Publications In 2022, Reagan K. Barfield, Matthew L. Brown, Benjamin Albrecht, Katie E. Barber, Jeannette Bouchard, Amy L. Carr, Elias B. Chahine, David Cluck, Elizabeth W. Covington, Connor R. Deri, Spencer H. Durham, Carmen Faulkner-Fennell, Lauren K. Freeman, Timothy P. Gauthier, Geneen M. Gibson, Sarah B. Green, Athena L.V. Hobbs, Bruce M. Jones, P. Brandon Bookstaver Pharm.D., Et. Al.

Faculty Publications

Keeping abreast of the antimicrobial stewardship–related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship–related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Therapeutics To Treat Psychiatric And Neurological Disorders: A Promising Perspective From Algerian Traditional Medicine, Farida Larit, Francisco León Ph.D.

Faculty Publications

Ancient people sought out drugs in nature to prevent, cure, and treat their diseases, including mental illnesses. Plants were their primary source for meeting their healthcare needs. In Algeria, folk medicine remains a fundamental part of the local intangible knowledge. This study aims to conduct a comprehensive ethnomedicinal investigation and documentation of medicinal plants and the different plant formulations traditionally used in Algeria for the treatment of pain, psychiatric, and neurological disorders. It also intends to improve the current knowledge of Algerian folk medicine. Several scientific databases were used to accomplish this work. Based on this investigation, we identified 82 …

Cdk8 And Cdk19: Positive Regulators Of Signal-Induced Transcription And Negative Regulators Of Mediator Complex Proteins, Mengqian Chen, Jing Li, Li Zhang, Lili Wang, Chen Cheng, Hao Ji, Serena Altilia, Xiaokai Ding, Guoshuai Cai, Diego Altomare, Michael Shtutman, Stephanie D. Byrum, Samuel G. Mackintosh, Alexey Feoktistov, Nataliya Soshnikova, Vladislav A. Mogila, Victor Tatarskiy, Maksim Erokhin, Darya Chetverina, Angga Prawira, Yi Ni, Stephan Urban, Campbell Mcinnes, Eugenia Broude, Igor Roninson

Faculty Publications

We have conducted a detailed transcriptomic, proteomic and phosphoproteomic analysis of CDK8 and its paralog CDK19, alternative enzymatic components of the kinase module associated with transcriptional Mediator complex and implicated in development and diseases. This analysis was performed using genetic modifications of CDK8 and CDK19, selective CDK8/19 small molecule kinase inhibitors and a potent CDK8/19 PROTAC degrader. CDK8/19 inhibition in cells exposed to serum or to agonists of NFκB or protein kinase C (PKC) reduced the induction of signal-responsive genes, indicating a pleiotropic role of Mediator kinases in signal-induced transcriptional reprogramming. CDK8/19 inhibition under basal conditions initially downregulated a small …

Racial And Ethnic Disparities In Alcohol-Attributed Deaths In The United States, 1999–2020, Ibraheem M. Karaye, Nasim Maleki, Ismaeel Yunusa Ph.D.

Faculty Publications

The disparities in alcohol-attributed death rates among different racial and ethnic groups in the United States (US) have received limited research attention. Our study aimed to examine the burden and trends in alcohol-attributed mortality rates in the US by race and ethnicity from 1999 to 2020. We used national mortality data from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database and employed the ICD-10 coding system to identify alcohol-related deaths. Disparity rate ratios were calculated using the Taylor series, and Joinpoint regression was used to analyze temporal trends and calculate annual and …

The Global Fatty Liver Disease-Sustainable Development Goal Country Score For 195 Countries And Territories, Jeffrey V. Lazarus, Hannah Han, Henry E. Mark, Saleh A. Schattenberg, Jörn M. J., Ismaeel Yunusa Ph. D., Et Al.

Faculty Publications

Background & Aims:

Fatty liver disease is highly prevalent, resulting in overarching wellbeing and economic costs. Addressing it requires comprehensive and coordinated multisectoral action. We developed a fatty liver disease-Sustainable Development Goal (SDG) country score to provide insights into country-level preparedness to address fatty liver disease through a whole-of-society lens.

Approach & Results:

We developed two fatty liver disease-SDG score sets. The first included six indicators (child wasting, child overweight, non-communicable disease [NCD] mortality, universal health coverage service coverage index, health worker density, and education attainment), covering 195 countries between 1990-2017. The second included the aforementioned indicators plus an urban …

Intensive Care Unit Mortality And Length Of Stay Among Critically Ill Patients With Sepsis Treated With Corticosteroids: A Retrospective Cohort Study, Eric E. Chinaeke, Ismaeel Yunusa Ph.D., Bryan L. Love Pharm. D., Joseph Magagnoli, Claiborne E. Reeder

Faculty Publications

Objectives: Sepsis is a major cause of morbidity and mortality in critically ill patients worldwide, and corticosteroids are commonly used to treat it. However, the evidence supporting the use of corticosteroids in sepsis patients admitted to the intensive care unit (ICU) is of low certainty, with conflicting results reported in previous studies. Thus, we aimed to investigate the potential association between corticosteroid treatment and various outcomes, including 30-day ICU mortality, ICU length of stay (LOS), mechanical ventilation use, new onset of infection, and hyperglycemia in patients diagnosed with sepsis and admitted to the ICU.

Materials and Methods: We conducted …

The Polypharmacological Effects Of Cannabidiol, Jorge Castillo-Arellano, Ana Canseco-Alba, Stephen J. Cutler Ph.D., Francisco León Ph.D.

Faculty Publications

Cannabidiol (CBD) is a major phytocannabinoid present in Cannabis sativa (Linneo, 1753). This naturally occurring secondary metabolite does not induce intoxication or exhibit the characteristic profile of drugs of abuse from cannabis like Δ⁹-tetrahydrocannabinol (∆⁹-THC) does. In contrast to ∆⁹-THC, our knowledge of the neuro-molecular mechanisms of CBD is limited, and its pharmacology, which appears to be complex, has not yet been fully elucidated. The study of the pharmacological effects of CBD has grown exponentially in recent years, making it necessary to generate frequently updated reports on this important metabolite. In this article, a …

Impacts Of Fda Approval And Medicare Restriction On Antiamyloid Therapies For Alzheimer’S Disease: Patient Outcomes, Healthcare Costs, And Drug Development, Rouen Brockmann, Joanna Nixon, Bryan L. Love Pharm D., Ismaeel Yunusa Ph. D.

Faculty Publications

In 2021, the US Food and Drug Administration (FDA) granted approval to aducanumab, an antiamyloid antibody for early-stage Alzheimer's disease, despite a lack of clear clinical evidence demonstrating the drug's cognitive benefits. The manufacturer initially priced the drug at a staggering $56,000 per year, a price that was later reduced to $28,200. Unfortunately, these costs do not include the additional expenses associated with monitoring the treatment. However, the Centers for Medicare and Medicaid Services (CMS) recently announced that they will only cover individuals enrolled in clinical trials and will limit coverage of future antiamyloid antibodies. This discrepancy between the FDA …

Comparative-Effectiveness Of Oral Beta-Lactams And Fluoroquinolones For Stepdown Therapy In Patients With Enterobacterales Bloodstream Infections: A Retrospective Cohort Study, Lauren Bjork Ph.D., Teri Hopkins Ph.D., Linda Yang Ph.D., Chengwen Teng Pharm.D., Ph.D., Xavier Jones Bs, Jose Cadena, Elizabeth Walter, Christopher R. Frei Pham.D., Ms

Faculty Publications

Background: This study compares treatment failure for patients who received oral beta-lactams (BLs) and fluoroquinolones (FQs) for stepdown treatment of Enterobacterales bloodstream infections (BSIs).

Methods: We conducted a single-center, retrospective, age- and sex-matched, cohort study, at a Veterans Affairs (VA) hospital in South Texas. Eligible patients were at least 18 years of age with a monomicrobial BSI treated with a single oral BL or FQ antibiotic. Treatment failure was defined as recurrence or all-cause mortality within 90 days of documented BSI. Bivariate (chi-square, Fisher's Exact, and Wilcoxon Rank Sum) and multivariate (logistic regression) statistical tests were used to compare groups. …