Pharmacy and Pharmaceutical Sciences Commons^™

Conditional Drug Approval As A Path To Market For Oncology Drugs In Canada: Challenges And Recommendations For Assessing Eligibility And Regulatory Responsiveness, Melanie Mcphail, Emma Weiss, Tania M. Bubela

Office of the Provost

International drug regulators use conditional drug approval mechanisms to facilitate faster patient access to drugs based on a lower evidentiary standard typically required of drug approvals. Faster and earlier access is justified by limiting eligibility to drugs intended for serious and life-threatening diseases and by requiring post-market evidence collection to confirm clinical benefit. One such mechanism in Canada, the Notice of Compliance with Conditions (NOC/c) policy, was introduced in 1998. Today, most of the drugs approved under the NOC/c policy are for oncology indications. We analyze oncology drugs approvals under the NOC/c policy to inform discussions of two tradeoffs applied …

Introduction To Medication Outcomes Php 509, Joanna Burkhardt

Library Impact Statements

No abstract provided.

The Natural Isoflavone Biochanin-A Synergizes 5-Fluorouracil Anticancer Activity In Vitro And In Vivo In Ehrlich Solid-Phase Carcinoma Model, Mohamed Mahmoud, Maha R.A. Abdollah, Mohamed E. Elsesy, Dalal A. Abou El Ella, Suher K. Zada, Mai Fathy Tolba

Pharmacy

Isoflavones are considered one of the most extensively studied plant-derived phytoestrogenic compounds. Of these, Biochanin A (Bio-A), a natural isoflavone abundant in cabbage, alfalfa, and red clover, has drawn a lot of attention. As reported in multiple studies, Bio-A possesses a promising anticancer activity against estrogen receptor–positive (ER+)  breast cancer. The current study investigated the working hypothesis that Bio-A could synergistically enhance the potency of 5-fluorouracil (5-FU) in ER+ breast cancer. The hypothesis was tested both in vitro on hormone receptor–positive (MCF-7) and triple-negative breast cancer cells (MDA-MB231). Additionally, in vivo studies were performed in the Ehrlich solid-phase carcinoma mouse …

Effects Of Metformin Combined With Antifolates On Hepg2 Cell Metabolism And Cellular Proliferation, Sherouk M. Tawfik, Maha R.A. Abdollah, M. M. Elmazar, Hassan A. N. El-Fawal, Anwar Abdelnaser

Pharmacy

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Furthermore, a growing body of evidence shows that cancer metabolic changes are a key feature of many types of human malignancies. Metabolic reprogramming refers to cancer cells’ ability to change their metabolism in order to meet the increased energy demand caused by continuous growth, rapid proliferation, and other neoplastic cell characteristics. For these reasons, …

The Influence Of Social Determinants Of Health On The Provision Of Postpartum Contraceptives In Medicaid, Irene Nsiah, Nidhi Vij Mali, Marie Barnard, Swarnali Goswami

Faculty and Student Publications

Disparities continue to exist in the timely provision of postpartum contraception. This study aimed to identify prevalence and factors associated with postpartum contraception provision among women enrolled in Medicaid. A retrospective cohort study was conducted using the 2014 National Medicaid data, linked to county‐level social vulnerability index (SVI) data. Women aged 15–44 with a live birth in 2014 were included. Multivariable logistic regression was used to predict 3‐day provision of long‐acting reversible contraception (LARC) and 60‐day provision of most effective or moderately effective contraceptives (MMEC). Overall, 3‐day LARC provision was 0.2% while 60‐day MMEC was 36.3%. Significantly lower odds of …

Phytochemical Screening, In Vitro And In Silico Studies Of Volatile Compounds From Petroselinum Crispum (Mill) Leaves Grown In Saudi Arabia, Ahmed I. Foudah, Mohammad H. Alqarni, Aftab Alam, Mohammad Ayman Salkini

Faculty and Student Publications

The herbal plant Petroselinum crispum (P. crispum) (Mill) is commonly available around the world. In this study, the leaves of the herbal plant P. crispum were collected from the central region of Al-Kharj, Saudi Arabia, to explore their in vitro pharmacological activity. Essential oil from the leaves of P. crispum was isolated using the hydrodistillation method. The composition of P. crispum essential oil (PCEO) was determined using Gas chromatography-mass spectrometry (GC-MS). A total of 67 components were identified, representing approximately 96.02% of the total volatile composi-tion. Myristicin was identified as the principal constituent (41.45%). The in vitro biological activity was …

A Multitarget Approach To Evaluate The Efficacy Of Aquilaria Sinensis Flower Extract Against Metabolic Syndrome, Hee Sung Chae, Olivia Dale, Tahir Maqbool Mir, Bharathi Avula

Faculty and Student Publications

Aquilaria sinensis (Lour.) Spreng is known for its resinous secretion (agarwood), often secreted in defense against injuries. We investigated the effects of A. sinensis flower extract (AF) on peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of PPARα, PPARγ and LXR was determined in hepatic (HepG2) cells by reporter gene assays. Glucose uptake was determined in differentiated muscle (C2C12) cells using 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose). Adipogenesis was determined in adipocytes (3T3-L1 cells) by Oil red O staining. At a concentration of 50 µg/mL, AF caused 12.2-fold activation of PPARα and …

Lip Reconstruction By Double Layer And Double Flap New Combination Technique: A Case Series, Antonio Cortese, Salvatore Catalano, Antonio Alberto Maria Giunta, Antonio Borri

Faculty and Student Publications

In the past, lip reconstruction after ablative surgery has been performed by primary closure and more recently by free flap transfer technique. Cheek’s skin flap has been used to reconstruct the lower lip cutaneous portion. This study presents a reconstructive method for the vermillion and the lip’s cutaneous portion using the Goldstein-Robotti techniques (for the vermillion) and the buccinator flap to reconstruct the cutaneous lip portion and the perioral muscles. This procedure allows a complete reconstruction with a double layer technique for defects of more than one-third of both lips, together or alone, including modiolus, showing satisfactory functionality and aesthetics. …

Do Formulation And Dose Of Long-Term Opioid Therapy Contribute To Risk Of Adverse Events Among Older Adults?, Monika Salkar, Sujith Ramachandran, John P. Bentley, Ike Eriator

Faculty and Student Publications

Background: Chronic non-cancer pain (CNCP) is highly prevalent in older adults and long-term opioid therapy (LTOT) has been used to manage chronic pain. However, the safety of LTOT among older adults with CNCP is not well-established and there is a need to identify therapy-related risk factors of opioid-related adverse events among older adults. Objective: To evaluate the relationship between opioid dose and formulation and the risk of opioid-related adverse events among Medicare-eligible older adults on LTOT. Design: Nested case-control study. Participants: Older Medicare beneficiaries (N=35,189) who received > 3 opioid prescriptions with a total days-supply of >45 days within a 90-day …

Type 2 Autoimmune Pancreatitis, Dr. Aniketh Hiremat, Dr Vikram Patil

Radiology Teaching Files

A 23-year-old female patient with no previous co-morbidities came to our hospital with a history of back pain for 4 days. No history of nausea/ vomiting/ loose stools/ fever/ melena/ hematemesis/ jaundice/ethanol abuse. The patient was not on any alternative medication. Physical examination was within normal limits. Serum amylase and lipase were elevated , measured 152U/L and 780 U/L respectively. AST/ ALT/ ALP were elevated , measured 88/139/308 respectively. Rest of the liver parameters and blood investigations were within normal limits.

Meconium Pseudocyst: A Case Report, Dr. Thasmai B R Gowda, Dr.Sushravya A S, Dr.Vikram Patil, Dr. Gurumurthy B, Priyanshi Tapadia

Radiology Teaching Files

No abstract provided.

Inhibition Of Interferon-Gamma-Stimulated Melanoma Progression By Targeting Neuronal Nitric Oxide Synthase (Nnos), Shirley Tong, Maris A. Cinelli, Naglaa Salem El-Sayed, He Huang, Anika Patel, Richard B. Silverman, Sun Yang

Pharmacy Faculty Articles and Research

Interferon-gamma (IFN-γ) is shown to stimulate melanoma development and progression. However, the underlying mechanism has not been completely defined. Our study aimed to determine the role of neuronal nitric oxide synthase (nNOS)-mediated signaling in IFN-γ-stimulated melanoma progression and the anti-melanoma effects of novel nNOS inhibitors. Our study shows that IFN-γ markedly induced the expression levels of nNOS in melanoma cells associated with increased intracellular nitric oxide (NO) levels. Co-treatment with novel nNOS inhibitors effectively alleviated IFN-γ-activated STAT1/3. Further, reverse phase protein array (RPPA) analysis demonstrated that IFN-γ induced the expression of HIF1α, c-Myc, and programmed death-ligand 1 (PD-L1), in contrast …

Frequency And Types Of Healthcare Encounters In The Week Preceding A Sepsis Hospitalization: A Systematic Review, Alexander H. Flannery, Chad M. Venn, Amanda Gusovsky, Stephanie Henderson, Adam S. Kiser, Hallie C. Prescott, Chanu Rhee, Chris Delcher, Peter E. Morris

Pharmacy Practice and Science Faculty Publications

OBJECTIVES: Early recognition and treatment are critical to improving sepsis outcomes. We sought to identify the frequency and types of encounters that patients have with the healthcare system in the week prior to a sepsis hospitalization.

DATA SOURCES: PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, and the Cochrane Library.

STUDY SELECTION: Observational cohort studies of patients hospitalized with sepsis or septic shock that were assessed for an outpatient or emergency department encounter with the healthcare system in the week prior to hospital admission.

DATA EXTRACTION: The primary outcome was the proportion of patients with a healthcare encounter …

Sars-Cov-2 Variants Increase Kinetic Stability Of Open Spike Conformations As An Evolutionary Strategy, Ziwei Yang, Yang Han, Shilei Ding, Wei Shi, Tongqing Zhou, Andrés Finzi, Peter D. Kwong, Walther Mothes, Maolin Lu

School of Medical and Biological Sciences Faculty Publications and Presentations

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) harbor mutations in the spike (S) glycoprotein that confer more efficient transmission and dampen the efficacy of COVID-19 vaccines and antibody therapies. S mediates virus entry and is the primary target for antibody responses, with structural studies of soluble S variants revealing an increased propensity toward conformations accessible to the human angiotensin-converting enzyme 2 (hACE2) receptor. However, real-time observations of conformational dynamics that govern the structural equilibriums of the S variants have been lacking. Here, we report single-molecule Förster resonance energy transfer (smFRET) studies of critical mutations observed in …

Race And Sex Associations With Tacrolimus Pharmacokinetics In Stable Kidney Transplant Recipients, Kathleen M. Tornatore, Calvin J. Meaney, Kristopher Attwood, Daniel A. Brazeau, Gregory E. Wilding, Joseph D. Consiglio, Aijaz Gundroo, Shrley S. Chang, Vanessa Gray, Louise M. Cooper, Rocco C. Venuto

Pharmaceutical Science and Research

Study Objective: This study investigated race and sex differences in tacrolimus pharmacokinetics and pharmacodynamics in stable kidney transplant recipients.

Design and Setting: A cross-sectional, open-label, single center, 12-h pharmacokinetic-pharmacodynamic study was conducted. Tacrolimus pharmacokinetic parameters included area under the concentration-time curve (AUC_0–12), AUC_0–4, 12-h troughs (C_{12 h}), maximum concentrations (C_max), oral clearance (Cl), with dose-normalized AUC_0–12, troughs, and C_max with standardized adverse effect scores. Statistical models were used to analyze end points with individual covariate-adjustment including clinical factors, genotypic variants CYP3A5*3, CYP3A5*6, CYP3A5*7(CYP3A5*3*6*7 …

Global, Regional, And National Sex Differences In The Global Burden Of Tuberculosis By Hiv Status, 1990-2019: Results From The Global Burden Of Disease Study 2019, Jorge R. Ledesma, Jianing Ma, Avina Vongpradith, Emilie R. Maddison, Amanda Novotney, Ismaeel Yunusa

Faculty Publications

Background Tuberculosis is a major contributor to the global burden of disease, causing more than a million deaths annually. Given an emphasis on equity in access to diagnosis and treatment of tuberculosis in global health targets, evaluations of differences in tuberculosis burden by sex are crucial. We aimed to assess the levels and trends of the global burden of tuberculosis, with an emphasis on investigating differences in sex by HIV status for 204 countries and territories from 1990 to 2019.

Methods We used a Bayesian hierarchical Cause of Death Ensemble model (CODEm) platform to analyse 21505 siteyears of vital registration …

Multicenter Retrospective Review Of Ketamine Use In The Icu., Christine M Groth, Christopher A Droege, Kathryn A Connor, Kimberly Kaukeinen, Nicole M Acquisto, Sai Ho J Chui, Michaelia D Cucci, Deepali Dixit, Alexander H Flannery, Kyle A Gustafson, Nina E Glass, Helen Horng, Mojdeh S Heavner, Justin Kinney, Rachel M Kruer, William J Peppard, Preeyaporn Sarangarm, Andrea Sikora, Velliyur Viswesh, Brian L Erstad, Parkview Health

Parkview Pharmacy Department

This publication is included in our collection because several Parkview pharmacists were involved in the data collection part and acknowledged for the assistance they provided to the overall article. See Comment.

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established.

OBJECTIVES: To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium.

DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients …

The Role Of The Accessory Gene Regulator Operon In Biofilm Formation By Staphylococcus Aureus, Sarah C. Jordan

Pharmaceutical Sciences ETDs

Staphylococcus aureus is a pathogenic bacteria that causes significant morbidity and mortality. As antibiotic resistance by S. aureus continues to be a serious concern, developing novel drug therapies to combat these infections is vital. Quorum sensing inhibitors (QSI) dampen S. aureus virulence and facilitate clearance by the host immune system by blocking quorum sensing signaling that promotes upregulation of the accessory gene regulator (agr) operon. While QSIs have shown therapeutic promise in mouse models of S. aureus infection, their further development has been hampered by the suggestion that agr inhibition promotes biofilm formation. In these studies, we investigated the relationship …

Online Graduate Certificate In Medication Outcomes, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Evaluation Of Step-Down Oral Antibiotic Therapy For Uncomplicated Streptococcal Bloodstream Infections On Clinical Outcomes, Amy Y. Kang, Richard Beuttler, Emi Minejima

Pharmacy Faculty Articles and Research

Background: Despite the severity and frequency of streptococcal bloodstream infections (BSIs), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the clinical outcomes of step-down oral antibiotics for the treatment of uncomplicated streptococcal BSIs.

Methods: In this retrospective cohort study, adult patients admitted with uncomplicated streptococcal BSI between June 2015 and June 2017 were included. Patients were excluded if they received <48 h of antibiotic therapy; therapy was started >48 h after first positive culture; had complicated infections of endocarditis, bone and joint infections, or central nervous system infections; Pitt bacteremia score (PBS) ⩾ 4; or failed to respond …