Medicine and Health Sciences Commons^™

Effectiveness And Safety Of Apixaban Vs Warfarin In Patients With Venous Thromboembolism With Risk Factors For Bleeding Or For Recurrences, Alexander T. Cohen, Janvi Sah, Amol D. Dhamane, Dionne M. Hines, Theodore Lee, Lisa Rosenblatt, Birol Emir, Allison Keshishian, Huseyin Yuce, Xuemei Luo

Publications and Research

Introduction

Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences.

Methods

Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia …

Soft X-Ray And Susceptibility Based Magnetic Resonance Imaging To Map Iron Distribution In Apples: Initial Results To Model Iron Storage In Water-Deficient Or Dehydrated Biological Tissue, Subhendra N. Sarkar, Eric Lobel, Evans Lespinasse, Zoya Vinokur, Analia Basilicata, Sonia Orellana, Maria Orellana, Aaliyah Salmon, Joanna Syska, Aravis Mcbroom, Jian Wang, Anam Riaz, Jodi-Ann Douglas

Publications and Research

Radiology departments have contributed significantly to greenhouse gases including release of toxic imaging contrast media to environment. We feel Radiology also has several spectroscopy and imaging tools that may apply to monitor and support cleaner environmental goals. The current manuscript is one of the firsts to prompt Radiology to move in that direction by non invasive imaging of bio metals that are less abundant in biological tissues but play key roles as co-factors in tissue structure and function. Conventional analytical tools are mostly invasive and cannot characterize the native oxidation states of bio metals. We chose carbohydrate matrix of metal-rich …

Effectiveness And Safety Of Apixaban Vs Warfarin Among Venous Thromboembolism Patients At High-Risk Of Bleeding, Alexander T. Cohen, Janvi Sah, A. D. Dhamane, Theodore Lee, Lisa Rosenblatt, Patrick Hlavacek, Birol Emir, Allison V. Keshishian, Huseyin Yuce, Xuemei Luo

Publications and Research

This study evaluated effectiveness and safety of apixaban versus warfarin among venous thromboembolism patients at high-risk of bleeding (defined as having at least one of the following bleeding risk factors: ≥75 years; used antiplatelet, NSAIDs, or corticosteroids; had prior gastrointestinal bleeding or gastrointestinal-related conditions; late stage chronic kidney disease). Adult venous thromboembolism patients initiating apixaban or warfarin with ≥1 bleeding risk factor were identified from Medicare and four commercial claims databases in the United States. To balance characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting was conducted. Cox proportional hazards models were used to estimate the risk …

Oral Anticoagulant Underutilization Among Elderly Patients With Atrial Fibrillation: Insights From The United States Medicare Database, Muhammad Bilal Munir, Patrick Hlavacek, Allison V. Keshishian, Jennifer D. Guo, Rajesh Mallampati, Mauricio Ferri, Cristina Russ, Birol Emir, Matthew Cato, Huseyin Yuce, Jonathan C. Hsu

Publications and Research

Background

Oral anticoagulants (OACs) mitigate stroke risk in patients with atrial fibrillation (AF). The study aim was to analyze prevalence and predictors of OAC underutilization.

Methods

Newly diagnosed AF patients with a CHA2DS2-VASc score ≥ 2 were identified from the US CMS Database (January 1, 2013–December 31, 2017). Patients were stratified based on having an OAC prescription versus not and the OAC prescription group was stratified by direct OAC (DOACs) versus warfarin. Multivariable logistic regression models were used to examine predictors of OAC underutilization.

Results

Among 1,204,507 identified AF patients, 617,611 patients (51.3%) were not prescribed an OAC during follow-up …

Effectiveness And Safety Of Oral Anticoagulants In Non-Valvular Atrial Fibrillation Patients With Prior Bleeding Events: A Retrospective Analysis Of Administrative Claims Databases, G. Y. H. Lip, Allison V. Keshishian, Amiee Kang, Xuemei Luo, Nipun Atreja, Yan Zhang, Patricia Schuler, Jenny Jiang, Huseyin Yuce, Steve Deitelzweig

Publications and Research

Introduction

There are a paucity of real-world data examining effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in nonvalvular atrial fibrillation (NVAF) patients with prior bleeding.

Methods

This retrospective analysis included data from 5 insurance claims databases and included NVAF patients prescribed OACs with prior bleeding. One-to-one propensity score matching was conducted between NOACs and warfarin and between NOACs in each database. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and MB.

Results

A total of 244,563 patients (mean age 77; 50% female) with prior bleeding included 55,094 (22.5%) treated …

An Evaluation Of The Effect Of The Oxycontin® Reformulation On Unintentional Fatal And Non-Fatal Overdose, Daniel C. Beachler, Kelsey Hall, Renu Garg, Geetanjoli Banerjee, Ling Li, Luke Boulanger, Huseyin Yuce, Alexander M. Walker

Publications and Research

Objectives: OxyContin® was reformulated with a polyethylene oxide matrix in August 2010 to reduce the potential for intravenous abuse and for abuse by insufflation. The objective of this study was to evaluate the impact of OxyContin’s reformulation on overdose risk for individuals dispensed OxyContin in comparison to those dispensed other opioids under regular care. Methods: Three national insurance databases with National Death Index linkage identified OD in individuals with any dispensing of OxyContin or a primary comparator opioid (ER morphine, transdermal fentanyl, or methadone) between July 2008 through September 2015. A difference-in-differences design was used to compare the pre-post reformulation …

Effectiveness And Safety Of Apixaban Versus Warfarin Among Older Patients With Venous Thromboembolism With Different Demographics And Socioeconomic Status, Alexander T. Cohen, Janvi Sah, Amol Dhamane, Theodore Lee, Lisa Rosenblatt, Patrick Hlavacek, Birol Emir, Allison V. Keshishian, Huseyin Yuce, Xuemei Luo

Publications and Research

Introduction

Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES.

Methods

Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014–December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, …

Covid-19 Multi-Targeted Drug Repurposing Using Few-Shot Learning, Yang Liu, You Wu, Xiaoke Shen, Lei Xie

Publications and Research

The life-threatening disease COVID-19 has inspired significant efforts to discover novel therapeutic agents through repurposing of existing drugs. Although multi-targeted (polypharmacological) therapies are recognized as the most efficient approach to system diseases such as COVID-19, computational multi-targeted compound screening has been limited by the scarcity of high-quality experimental data and difficulties in extracting information from molecules. This study introduces MolGNN , a new deep learning model for molecular property prediction. MolGNN applies a graph neural network to computational learning of chemical molecule embedding. Comparing to state-of-the-art approaches heavily relying on labeled experimental data, our method achieves equivalent or superior prediction …

Oral Anticoagulants For Nonvalvular Atrial Fibrillation In Frail Elderly Patients: Insights From The Aristophanes Study, G. Y. H. Lip, A. V. Keshishian, A. L. Kang, A. D. Dhamane, X. Luo, X. Li, N. Balachander, L. Rosenblatt, J. Mardekian, X. Pan, M. Di Fusco, A. B. Garcia Reeves, Huseyin Yuce, S. Deitelzweig

Publications and Research

Background

Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population.

Objectives

This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin.

Methods

This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013‐30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare …

A Role For Retinoids In The Treatment Of Covid-19?, Steven E. Trasino

Publications and Research

The 2020 global outbreak of the novel coronavirus (SARS-CoV-2 or COVID-19) is a serious threat to international health, and thus, there is an urgent need for discoverynof novel therapies or use of repurposed drugs that can make a significant impact on slowing the spread of the virus. Type 1 interferons (IFN-I) are a family cytokines of the early innate immune response to viruses that are being tested against SARSCoV- 2. However, coronaviruses similar to SARS-CoV-2 can suppress host IFN-I antiviral responses. Retinoids are a family molecules related to vitamin A that possess robust immune-modulating properties, including the ability to increase …

A Real-World Analysis Of Patient Characteristics And Predictors Of Hospitalization Among Us Medicare Beneficiaries With Respiratory Syncytial Virus Infection, Veronique Wyffels, Furaha Kariburyo, Sandra Gavart, Roman Fleischhackl, Huseyin Yuce

Publications and Research

Introduction: Little has been published on respiratory syncytial virus (RSV) among Medicare patients at high risk (HR) of RSV complications due to age or comorbidity. Methods: Adult patients (at least 18 years of age) with at least 1 diagnostic code for RSV were identified using the 5% US Medicare database from 2011 through 2015. Patients were required to have continuous health plan enrollment for 180 days pre- and 180 days post-RSV diagnosis (baseline and follow-up periods, respectively). HR was defined as diagnosis of chronic lung disease, congestive heart failure, or weakened immune system for 180 days during the base-line period. …

Polymers For Extrusion‐Based 3d Printing Of Pharmaceuticals: A Holistic Materials–Process Perspective, Mohammad A. Azad, Deborah Olawuni, Georgia Kimbell, Abu Zayed Badruddoza, Md. Shahadat Hossain, Tasnim Sultana

Publications and Research

Three dimensional (3D) printing as an advanced manufacturing technology is progressing to be established in the pharmaceutical industry to overcome the traditional manufacturing regime of ʹone size fits for allʹ. Using 3D printing, it is possible to design and develop complex dosage forms that can be suitable for tuning drug release. Polymers are the key materials that are necessary for 3D printing. Among all 3D printing processes, extrusion‐based (both fused deposition modeling (FDM) and pressure‐assisted microsyringe (PAM)) 3D printing is well researched for pharmaceutical manufacturing. It is important to understand which polymers are suitable for extrusion‐based 3D printing of pharmaceuticals …

Treatment Patterns And Economic Burden Of Sickle-Cell Disease Patients Prescribed Hydroxyurea: A Retrospective Claims-Based Study, Nirmish Shah, Menaka Bhor, Lin Xie, Rashid Halloway, Steve Arcona, Jincy Paulose, Huseyin Yuce

Publications and Research

Background: This study aimed to evaluate sickle-cell disease (SCD) treatment patterns and economic burden among patients prescribed hydroxyurea (HU) in the US, through claims data.

Methods: SCD patients with pharmacy claims for HU were selected from the Medicaid Analytic Extracts (MAX) from January 1, 2009 - December 31, 2013. The first HU prescription during the identification period was defined as the index date and patients were required to have had continuous medical and pharmacy benefits for ≥6 months baseline and 12 months follow-up periods. Patient demographics, clinical characteristics, treatment patterns, health care utilization, and costs were examined, and variables were …

Preclinical Evaluation Of An Unconventional Ruthenium‐Gold‐ Based Chemotherapeutic: Rance‐1, In Clear Cell Renal Cell Carcinoma, Benelita Elie, Karen Hubbard, Yuriy Pechenyy, Buddhadev Layek, Swayam Prabha, Maria Contel

Publications and Research

Background: There are few effective treatments for patients with advanced clear cell renal cell carcinoma (CCRCC). Recent findings indicate that ruthenium‐gold containing compounds exhibit significant antitumor efficacy against CCRCC in vitro affecting cell viability as well as angiogenesis and markers driving those 2 phenomena. However, no in vivo preclinical evaluation of this class of compounds has been reported.

Methods: Following the dose‐finding pharmacokinetic determination, NOD. CB17‐Prkdc SCID/J mice bearing xenograft CCRCC Caki‐1 tumors were treated in an intervention trial for 21 days at 10 mg/kg/72h of RANCE‐1. At the end of the trial, tumor samples were analyzed for histopathological and …

Case Presentation On Congestive Heart Failure And Pulmonary Edema, Tetiana Soloviova, Denise Aris

Publications and Research

No abstract provided.

Comparative Characteristics Of Antibacterial Activity Of Plants Growing In The Central Part Of The Republic Of Tajikistan., Saidbeg Satorov, F. Mirzoeva, Sh. Satorov, M. Vakhidova, Vyacheslav Dushenkov

Publications and Research

Objective: To evaluate the spectrum of antibacterial activity of plants growing in the central part of the Republic of Tajikistan.
Methods: The antibacterial properties of 18 plant species from the 14 families were studied. The extract samples on dry filter discs were prepared according to the method developed at Rutgers University. Screens-to-Nature (STN) and disc diffusion (DD) methods were used to assess antimicrobial properties of the extracts. The antimicrobial activity of plant extracts was determined against four types of pathogenic standard museum strains of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, as well as …

Structure-Activity Profiling Of Alkaloid Natural Product Pharmacophores Against A Schistosoma Serotonin Receptor, Jonathan S. Marchant, Wayne W. Harding, John D. Chan

Publications and Research

Serotonin (5-HT) is an important regulator of numerous aspects of flatworm biology, ranging from neuromuscularfunctionto sexualmaturationandegglaying. Intheparasiticblood flukeSchistosomamansoni,5-HTtargets several G-protein coupled receptors (GPCRs), one of which has been demonstrated to couple to cAMP and regulate parasite movement. This receptor, Sm.5HTRL, has been successfully co-expressed in mammalian cells alongside a luminescent cAMP-biosensor, enabling pharmacological profiling for candidate anti-schistosomal drugs. Here, we have utilized this assay to perform structure-activity investigations of 143 compounds containing previously identified alkaloid natural product pharmacophores (tryptamines, aporphines and protoberberines) shown to regulate Sm.5HTRL. These experiments mapped regions of the tryptamine pharmacophore amenable and intolerant to substitution, highlighting …

Chronic Voluntary Oral Methamphetamine Induces Deficits In Spatial Learning And Hippocampal Protein Kinase Mzeta With Enhanced Astrogliosis And Cyclooxygenase-2 Levels, Jorge A. Avila, Roseanna M. Zanca, Denis Shor, Nicholas Paleologos, Amber A. Alliger, Maria E. Figueiredo-Pereira, Peter A. Serrano

Publications and Research

Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA. This VOMA model is useful for determining the lower limits necessary to produce neurotoxicity in the …

Impact Of Health Policy Changes On Emergency Medicine In Maryland Stratified By Socioeconomic Status, Laura Pimentel, David Anderson, Bruce Golden, Edward Wasil, Fermin Barreuto, Jon M. Hirshon

Publications and Research

Introduction: On January 1, 2014, the financing and delivery of healthcare in the state of Maryland (MD) profoundly changed. The insurance provisions of the Patient Protection and Affordable Care Act (ACA) began implementation and a major revision of MD’s Medicare waiver ushered in a Global Budget Revenue (GBR) structure for hospital reimbursement. Our objective was to analyze the impact of these policy changes on emergency department (ED) utilization, hospitalization practices, insurance profiles, and professional revenue. We stratified our analysis by the socioeconomic status (SES) of the ED patient population.

Methods: We collected monthly mean data including patient volume, hospitalization percentages, …

Awareness And Knowledge Among Internal Medicine House-Staff For Dose Adjustment Of Commonly Used Medications In Patients With Ckd, Sikander Surana, Neeru Kumar, Amita Vasudeva, Gulvahid Shaikh, Kenar D. Jhaveri, Hitesh Shah, Deepa Malieckal, Joshua Fogel, Gurwinder Sidhu, Sofia Rubinstein

Publications and Research

Background: Drug dosing errors result in adverse patient outcomes and are more common in patients with chronic kidney disease (CKD). As internists treat the majority of patients with CKD, we study if Internal Medicine house-staff have awareness and knowledge about the correct dosage of commonly used medications for those with CKD. Methods: A cross-sectional survey was performed and included 341 participants. The outcomes were the awareness of whether a medication needs dose adjustment in patients with CKD and whether there was knowledge for the level of glomerular filtration rate (GFR) a medication needs to be adjusted. Results: The overall pattern …

Polyphenols Content And Antioxidant Activity Of Artemisia Sieversiana Willd. In Western Pamir, Gulazor Miravalova, Sh. Kurbonbekova, Sh. Satorov, Akobir Mirzorahimov, Dovudsho Navruzshoev, Vyacheslav Dushenkov, M. Vakhidova

Publications and Research

Polyphenols content and antioxidant activity in Artemisia sieversiana Willd. were investigated in relation to the altitude of the plant growth in the Western Pamir region. Antioxidant activity generally correlated with the polyphenols content. However, no significant association was found between an altitude of the sample collection and polyphenols content or antioxidant activity.

Gastrointestinal Safety, Chemotherapeutic Potential, And Classic Pharmacological Profile Of Nosh-Naproxen (Avt-219) A Dual No- And H2s-Releasing Hybrid, Mitali Chattopadhyay, Ravinder Kodela, Pascale L. Duvalsaint, Khosrow Kashfi

Publications and Research

Naproxen (NAP) is a potent nonsteroidal anti-inflammatory drug (NSAID) with a favorable cardiovascular profile. However, its long-term use may lead to serious gastrointestinal and renal side effects. NOSH- (nitric oxide and hydrogen sulfide) releasing naproxen (NOSH-NAP, AVT-219) belongs to a new class of anti-inflammatory agents designed to overcome these limitations. We compared the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, and antiplatelet properties of AVT-219 to that of NAP in preclinical animal models. We also evaluated its anticancer effects in 11 human cancer cell (HCC) lines of six different tissue origins and in a chemotherapeutic xenograft mouse model of colon cancer. AVT-219: …

Nosh-Aspirin (Nbs-1120), A Dual Nitric Oxide And Hydrogen Sulfide-Releasing Hybrid, Reduces Inflammatory Pain, Miriam D. Fonseca, Fernando Q. Cunha, Khosrow Kashfi, Thiago M. Cunha

Publications and Research

The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S donors into aspirin (NOSH-aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain. It was found that NOSH-aspirin inhibits acetic acid-induced writhing response and carrageenan (Cg)-induced inflammatory hyperalgesia in a dosedependent (5–150 lmol/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. NOSH-aspirin’s antinociceptive effect was also …

Flurbiprofen Benzyl Nitrate (Nbs-242) Inhibits The Growth Of A-431 Human Epidermoid Carcinoma Cells And Targets Β-Catenin, Niharika Nath, Xiaoping Liu, Lloydine Jacobs, Khosrow Kashfi

Publications and Research

Background: The Wnt/β-catenin/T cell factor (TCF) signaling pathway is important in the development of nonmelanoma skin cancers (NMSCs). Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemopreventive agents consisting of a traditional NSAID attached to an NO-releasing moiety through a chemical spacer. Previously we showed that an aromatic spacer enhanced the potency of a particular NO-NSAID compared to an aliphatic spacer.

Methods: We synthesized an NO-releasing NSAID with an aromatic spacer (flurbiprofen benzyl nitrate, NBS-242), and using the human skin cancer cell line A-431, we evaluated its effects on cell kinetics, Wnt/β-catenin, cyclin D1, and caspase-3.

Results: NBS-242 inhibited the growth of …

A Quantitative Synthesis Of The Medicinal Ethnobotany Of The Malinké Of Mali And The Asháninka Of Peru, With A New Theoretical Framework, Nathaniel Bletter

Publications and Research

Background: Although ethnomedically and taxonomically guided searches for new medicinal plants can improve the percentage of plants found containing active compounds when compared to random sampling, ethnobotany has fulfilled little of its promise in the last few decades to deliver a bounty of new, laboratory-proven medicinal plants and compounds. It is quite difficult to test, isolate, and elucidate the structure and mechanism of compounds from the plethora of new medicinal plant uses described each year with limited laboratory time and resources and the high cost of clinical trials of new drug candidates.

Methods: A new quantitative theoretical framework of mathematical …

Up-Regulation Of Neuronal Calcium Sensor-1 (Ncs-1) In The Prefrontal Cortex Of Schizophrenic And Bipolar Patients, Phil Ok Koh, Ashiwel S. Undieh, Robert Levenson, Patricia S. Goldman-Rakic, Michael S. Lidow

Publications and Research

The delineation of dopamine dysfunction in the mentally ill has been a long-standing quest of biological psychiatry. The present study focuses on a recently recognized group of dopamine receptor- interacting proteins as possible novel sites of dysfunction in schizophrenic and bipolar patients. We demonstrate that the dorsolateral prefrontal cortex in schizophrenia and bipolar cases from the Stanley Foundation Neuropathology Consortium display significantly elevated levels of the D2 dopamine receptor desensitization regulatory protein, neuronal calcium sensor-1. These levels of neuronal calcium sensor-1 were not influenced by age, gender, hemisphere, cause of death, postmortem period, alcohol consumption, or antipsychotic and mood stabilizing …

Timing Of New Black Box Warnings And Withdrawals For Prescription Medications, Karen Lasser, Paul D. Allen, Steffie Woolhandler, David U. Himmelstein, Sidney M. Wolfe, David H. Bor

Publications and Research

Context Recently approved drugs may be more likely to have unrecognized adverse drug reactions (ADRs) than established drugs, but no recent studies have examined how frequently postmarketing surveillance identifies important ADRs.

Objective To determine the frequency and timing of discovery of new ADRs described in black box warnings or necessitating withdrawal of the drug from the market.

Design and Setting Examination of the Physicians' Desk Reference for all new chemical entities approved by the US Food and Drug Administration between 1975 and 1999, and all drugs withdrawn from the market between 1975 and 2000 (with or without a prior black …