Medicine and Health Sciences Commons^™

Genetic Assessment Of Hyperuricemia And Gout In Asian, Native Hawaiian, And Pacific Islander Subgroups Of Pregnant Women: Biospecimens Repository Cross-Sectional Study, Ali Alghubayshi, Alison Edelman, Khalifa Alrajeh, Youssef Roman

Pharmacotherapy and Outcomes Science Publications

Background

Gout, an inflammatory condition, is characterized by the precipitation of monosodium urate crystals (MSU) in or around distal joints. The latter is caused by chronic hyperuricemia (HU)—high urate levels in the blood. Genetic variations in urate transporters play a significant role in determining urate levels within the human body, rendering some racial and ethnic groups more or less susceptible to developing either HU or gout. This study aims to estimate the frequencies of HU and gout risk alleles in Asian, Native Hawaiian, and Pacific Islander subgroups, using biorepository DNA samples.

Methods

The biospecimens repository at the University of Hawai’i …

Acute Fish Oil Supplementation And Aspirin Treatment Modulates Lipid Profile In Platelet Rich Plasma: A Randomized Pilot Trial, Joshua M. Morriss, Lisa A. Turner, Danielle M. Mccormack, Daniel Contaifer, Naren Gajenthra Kumar, Saidheeraj Paravataneni, Monther Alsultan, Suad Alshammari, Silas Contaifer, Parthasarathy Madurantakam, Dayanjan Wijesinghe

Pharmacotherapy and Outcomes Science Publications

Aims: Platelet rich plasma (PRP) has been used in tissue repair to treat numerous inflammatory pathophysiologies. Recent studies have elucidated that the bioactive lipid fraction of PRP significantly contributes towards the resolution of inflammation. There has been great interest in how therapeutics could modulate the PRP lipidome to formulate a more pro-resolving matrix. Many of the pathways used to produce either pro-resolving or pro-inflammatory lipids are shared between ω-3 and ω-6 polyunsaturated fatty acids (PUFA). Here, we explored the separate and interacting effects acute exogenous ω-3 PUFA supplementation and aspirin had on the lipidome of PRP within 6 hours.

Methods: …

Providers’ Perception Of Alert Fatigue After Implementation Of User-Filtered Warnings, Hina Afaq, Sahaana Mukundan, Sadaf Zia, Alisa K. Escano Dr., Rebecca Lear Dr., Casey Washington Dr.

Pharmacotherapy and Outcomes Science Publications

Alert fatigue is a complex problem that many health institutions face when using an electronic health record (EHR). The addition of user-filtered warnings (UFW) is a physicians’ proposed intervention at Inova Health System (IHS), a large 5-hospital health system in Northern Virginia, that allows prescribers to filter out specific drug-drug interactions and pregnancy and lactation medication alerts for a 30-day period. This study aims to determine the impact of UFW on physicians’ perception of alert fatigue and to calculate the reduction of medication alerts. It was hypothesized that the reduction in alerts will significantly impact physicians’ perception of alert fatigue …

A Preliminary Investigation Towards The Risk Stratification Of Allogeneic Stem Cell Recipients With Respect To The Potential For Development Of Gvhd Via Their Pre-Transplant Plasma Lipid And Metabolic Signature, Daniel Contaifer Jr., Catherine H. Roberts, Naren Gajenthra Kumar, Ramesh Natarajan, Bernard J. Fisher, Kevin Leslie, Jason Reed, Amir A. Toor, Dayanjan S. Wijesinghe

Pharmacotherapy and Outcomes Science Publications

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unrelated donor SCT, or autologous SCT. Blood samples were taken following conditioning and prior to transplant on day 0 and the …

Metabolic Modulation Predicts Heart Failure Tests Performance, Daniel Contaifer Jr., Leo F. Buckley, George Wohlford, Naren G. Kumar, Joshua M. Morriss, Asanga D. Ranasinghe, Salvatore Carbone, Justin M. Canada, Cory Trankle, Antonio Abbate, Benjamin W. Van Tassell, Dayanjan S. Wijesinghe

Pharmacotherapy and Outcomes Science Publications

The metabolic changes that accompany changes in Cardiopulmonary testing (CPET) and heart failure biomarkers (HFbio) are not well known. We undertook metabolomic and lipidomic phenotyping of a cohort of heart failure (HF) patients and utilized Multiple Regression Analysis (MRA) to identify associations to CPET and HFBio test performance (peak oxygen consumption (Peak VO₂), oxygen uptake efficiency slope (OUES), exercise duration, and minute ventilation-carbon dioxide production slope (VE/VCO₂ slope), as well as the established HF biomarkers of inflammation C-reactive protein (CRP), beta-galactoside-binding protein (galectin-3), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP)). A cohort of 49 patients with …

Untargeted Lipidomic Analysis To Broadly Characterize The Effects Of Pathogenic And Non-Pathogenic Staphylococci On Mammalian Lipids, Naren Gajenthra Kumar, Daniel Contaifer Jr., Paul Rs Baker, Kim Ekroos, Kimberly K. Jefferson, Dayanjan S. Wijesinghe

Pharmacotherapy and Outcomes Science Publications

Modification of the host lipidome via secreted enzymes is an integral, but often overlooked aspect of bacterial pathogenesis. In the current era of prevalent antibiotic resistance, knowledge regarding critical host pathogen lipid interactions has the potential for use in developing novel antibacterial agents. While most studies to date on this matter have focused on specific lipids, or select lipid classes, this provides an incomplete picture. Modern methods of untargeted lipidomics have the capacity to overcome these gaps in knowledge and provide a comprehensive understanding of the role of lipid metabolism in the pathogenesis of infections. In an attempt to determine …

Identifying Medication Management Smartphone App Features Suitable For Young Adults With Developmental Disabilities: Delphi Consensus Study, Teresa M. Salgado, Alexa Fedrigon, Donna Riccio Omichinski, Michelle A. Meade, Karen B. Farris

Pharmacotherapy and Outcomes Science Publications

Background: Smartphone apps can be a tool to facilitate independent medication management among persons with developmental disabilities. At present, multiple medication management apps exist in the market, but only 1 has been specifically designed for persons with developmental disabilities. Before initiating further app development targeting this population, input from stakeholders including persons with developmental disabilities, caregivers, and professionals regarding the most preferred features should be obtained.

Objective: The aim of this study was to identify medication management app features that are suitable to promote independence in the medication management process by young adults with developmental disabilities using a Delphi consensus …

Variability In Antifungal Utilization Among Neonatal, Pediatric, And Adult Inpatients In Academic Medical Centers Throughout The United States Of America, Jeremy S. Stultz, Rose Kohinke, Amy L. Pakyz

Pharmacotherapy and Outcomes Science Publications

Background
Identification of factors associated with antifungal utilization in neonatal, pediatric, and adult patient groups is needed to guide antifungal stewardship initiatives in academic medical centers.

Methods
For this hospital-level analysis, we analyzed antifungal use in hospitals across the United States of America, excluding centers only providing care for hematology/oncology patients. Analysis of variance was used to compare antifungal use between patient groups. Three multivariable linear regression models were used to determine independent factors associated with antifungal use in the neonatal, pediatric, and adult patient groups.

Results
For the neonatal, pediatric, and adult patient groups, 54, 44, and 60 hospitals …

Impaired Myocardial Relaxation With Exercise Determines Peak Aerobic Exercise Capacity In Heart Failure With Preserved Ejection Fraction, Cory Trankle, Justin M. Canada, Leo Buckley, Salvatore Carbone, Dave Dixon, Ross Arena, Benjamin Van Tassell, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Background

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity due to shortness of breath and/or fatigue. Assessment of diastolic dysfunction at rest and with exercise may provide insight into the pathophysiology of exercise intolerance in HFpEF.

Aims

To measure echocardio-Doppler-derived parameters of diastolic function as they relate to various indices of aerobic exercise capacity in HFpEF.

Methods

We selected 16 subjects with clinically stable HFpEF, no evidence of volume overload, but impaired functional capacity by cardiopulmonary exercise testing [peak oxygen consumption (VO₂)]. We measured the transmitral E and A flow …

Chronic Health Conditions As A Risk Factor For Falls Among The Community-Dwelling Us Older Adults: A Zero-Inflated Regression Modeling Approach, Yoshita Paliwal, Patricia W. Slattum, Scott M. Ratliff

Pharmacotherapy and Outcomes Science Publications

Falls are an important health concern among older adults due to age-related changes in the body. Having a medical history of chronic health condition may pose even higher risk of falling. Only few studies have assessed a number of chronic health conditions as risk factor for falls over a large nationally representative sample of US older adults. In this study, Behavioral Risk Factor Surveillance System (BRFSS) 2014 participants aged 65 years and older (n = 159,336) were evaluated. It was found that 29.7% (n = 44,550) of the sample experienced at least one fall and 16.3% (n = 20,444) …

The Association Between Sleep Problems, Sleep Medication Use, And Falls In Community-Dwelling Older Adults: Results From The Health And Retirement Study 2010, Yaena Min, Pramit A. Nadpara, Patricia W. Slattum

Pharmacotherapy and Outcomes Science Publications

Background. Very few studies have assessed the impact of poor sleep and sleep medication use on the risk of falls among community-dwelling older adults. The objective of this study was to evaluate the association between sleep problems, sleep medication use, and falls in community-dwelling older adults. Methods. The study population comprised a nationally representative sample of noninstitutionalized older adults participating in the 2010 Health and Retirement Study. Proportion of adults reporting sleep problems, sleep medication use, and fall was calculated. Multiple logistic regression models were constructed to examine the impact of sleep problems and sleep medication use on …

Critical Appraisal Of Dabigatran In The Treatment Of Deep Vein Thrombosis And Pulmonary Embolism, Kelechi C. Ogbonna, Dave L. Dixon

Pharmacotherapy and Outcomes Science Publications

Objective

To compare the safety and efficacy of dabigatran to warfarin for the treatment of deep vein thrombosis and pulmonary embolism.

Background

Venous thromboembolism (VTE) is a disease comprised of two conditions: deep vein thrombosis and pulmonary embolism. VTE is a major cause of morbidity and mortality worldwide with an annual incidence estimated at 1–3 cases per 1,000 individuals. This incidence increases with age from 0.1 per 1,000 in adolescence to eight per 1,000 in those 80 years of age and older. As the proportion of patients 65 years of age and older expands, the number of patients presenting with …

Role Of Interleukin-1 In Radiation-Induced Cardiomyopathy, Eleonora Mezzaroma, Ross B. Mikkelsen, Stefano Toldo, Adolfo G. Mauro, Khushboo Sharma, Carlo Marchetti, Asim Alam, Benjamin W. Van Tassell, David A. Gewirtz, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in the mouse. Female mice with genetic deletion of the IL-1 receptor type I (IL-1R1 knockout mice [IL-1R1 KO]) and treatment with recombinant human IL-1 receptor antagonist anakinra, 10 mg/kg twice daily for 7 d, were used as independent approaches to determine the role of IL-1. …

Enhanced Interleukin-1 Activity Contributes To Exercise Intolerance In Patients With Systolic Heart Failure, Benjamin W. Van Tassell, Ross A. Arena, Stefano Toldo, Eleonora Mezzaroma, Tania Azam, Ignacio M. Seropian, Keyur Shah, Justin Canada, Norbert F. Voelkel, Charles A. Dinarello, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Background

Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects.

Methods and Results

We developed a model of IL-1β-induced left ventricular (LV) dysfunction in healthy mice that exhibited a 32% reduction in LV fractional shortening (P

Conclusions

These findings suggest that IL-1β activity contributes to poor exercise tolerance in patients with systolic HF and identifies …

Atorvastatin With Or Without An Antibody To Pcsk9 In Primary Hypercholesterolemia, Eli M. Roth, James M. Mckenny, Corinne Hanotin, Gaelle Asset, Evan A. Stein

Pharmacotherapy and Outcomes Science Publications

Background

Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels.

Methods

We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to …

Influence Of Continuous Venovenous Hemofiltration And Continuous Venovenous Hemodiafiltration On The Disposition Of Doripenem, Iolanda Cirillo, Nicole Vaccaro, Dainius Balis, Rebecca Redman, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The pharmacokinetics, safety, and tolerability of a single 1-hour, 500-mg intravenous infusion of doripenem were assessed in dialysis-dependent subjects with stage 5 chronic kidney disease undergoing continuous renal replacement therapy (CRRT) via 12-hour continuous venovenous hemofiltration (CVVH) (n = 6) or continuous venovenous hemodiafiltration (CVVHDF) (n = 5). Healthy volunteers were also assessed (n = 12). Concentrations of doripenem and the primary metabolite doripenem-M-1 were measured in plasma and ultrafiltrate or ultrafiltrate/dialysate by a validated liquid chromatography-tandem mass spectrometry method. In dialysis-dependent subjects, levels of systemic exposure to doripenem and doripenem-M-1 were approximately 3- and 5-fold greater, respectively, than those …

Effect Of Ceftazidime On Systemic Cytokine Concentrations In Rats, Khalid M. Alkharfy, John A. Kellum, Reginald F. Frye, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The effect of a single dose of ceftazidime on circulating concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in a rat model of sepsis was studied. IL-6 concentrations were significantly elevated (100 to 200 times the baseline) 6 h after ceftazidime administration in both septic and nonseptic (control) rats. TNF-α concentrations increased significantly in nonseptic (∼40 times the baseline) rats but not septic (∼2 to 3 times the baseline) rats. Ceftazidime administration was not associated with an increase in endotoxin concentrations. These findings suggest that ceftazidime modulation of proinflammatory cytokine concentrations may be independent of its antimicrobial properties.

Determinants Of Ceftazidime Clearance By Continuous Venovenous Hemofiltration And Continuous Venovenous Hemodialysis, Gary R. Matzke, Reginald F. Frye, Melanie S. Joy, Paul M. Palevsky

Pharmacotherapy and Outcomes Science Publications

Although several dosage adjustment regimens have been proposed, there is little quantitative information to guide the initiation of ceftazidime therapy in patients who are receiving continuous renal replacement therapy. To determine the clearance of ceftazidime by continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies with stable hemodialysis patients with three hemofilters: a 0.6-m2 acrylonitrile copolymer (AN69; Hospal) filter, a 2.1-m2 polymethylmethacrylate filter (PMMA; Toray) filter and a 0.65-m2 polysulfone (PS; Fresenius) filter. Subjects received 1,000 mg of ceftazidime intravenously prior to the start of a clearance study. The concentration of ceftazidime in multiple plasma …

Safety And Pharmacokinetics Of Multiple Doses Of Intravenous Ofloxacin In Healthy Volunteers, David R. P. Guay, John A. Opsahl, F. Gilbert Mcmahon, Ramon Vargas, Gary R. Matzke, Soledad Flor

Pharmacotherapy and Outcomes Science Publications

The safety and pharmacokinetics of ofloxacin in 48 healthy male volunteers were studied in a two-center, randomized, double-blind, placebo-controlled study. Ofloxacin (200 or 400 mg) or placebo was administered as 1-h infusions every 12 h for 7 days. Plasma ofloxacin concentrations were measured by high-performance liquid chromatography. Mean harmonic half-lives ranged from 4.28 to 4.98 h in the 200-mg dosing group and from 5.06 to 6.67 h in the 400-mg dosing group. Intragroup comparisons of trough plasma concentration-versus-time data from study days 2 through 7 revealed that steady state was achieved by day 2 of both multiple-dose regimens. Intergroup comparisons …

Pharmacokinetics Of Ceftibuten-Cis And Its Trans Metabolite In Healthy Volunteers And In Patients With Chronic Renal Insufficiency, Judy Shepard Kelloway, Walid M. Awni, Chin C. Lin, Josephine Lim, Melton B. Affrime, William F. Keane, Gary R. Matzke, Charles E. Halstenson

Pharmacotherapy and Outcomes Science Publications

The impact of renal insufficiency on the dispositions of 300 mg of orally administered ceftibuten-cis, a new broad-spectrum oral cephalosporin, and its primary metabolite ceftibuten-trans was characterized in 30 adult subjects. Subjects were divided into five groups of six subjects each on the basis of their 24-h ambulatory creatinine clearances (CL_CR). The apparent total body clearance (CL_P/F; where F is absolute bioavailability) and renal clearance of ceftibuten-cis were significantly lower in subjects with end-stage renal disease (on maintenance hemodialysis; group V) and in those with severe (CL_CR, 5 …

Pharmacokinetics Of Cefepime In Patients With Respiratory Tract Infections, J. M. Kovarik, J. C. Ter Maaten, C. M. A. Rademaker, M. Deenstra, I. M. Hoepelman, H. C. Hart, Gary R. Matzke, J. Verhoef

Pharmacotherapy and Outcomes Science Publications

The steady-state pharmacokinetics of cefepime were evaluated in 10 middle-aged and elderly patients with acute lower respiratory tract infections who were receiving 1 g intravenously every 12 h. One preinfusion and 15 postinfusion serum samples and total urine output were collected over one dosing interval between days 3 and 8 of therapy. Cefepime concentrations in serum over time exhibited a multicompartmental profile. Peak and trough concentrations in serum determined by a validated high-performance liquid chromatography method were 71.2 +/- 17.2 (mean +/- standard deviation) and 6.0 +/- 4.9 mg/liter, respectively. The steady-state volume of distribution was 0.22 +/- 0.05 liter/kg. …

Apparent Biliary Pseudolithiasis During Ceftriaxone Therapy, Karen L. Heim-Duthoy, Erskine M. Caperton, Robert Pollock, Gary R. Matzke, Dirk Enthoven, Phillip K. Peterson

Pharmacotherapy and Outcomes Science Publications

Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. To examine this phenomenon further, serial gallbladder sonograms were evaluated in 44 adult patients who received intravenous ceftriaxone at 2 g or a placebo daily for 14 days in a double-blind controlled study. Ultrasound examinations of gallbladders were performed on days 1 and 14 of therapy and 2 weeks posttherapy if abnormalities were observed on day 14. Eight patients were unevaluable because of abnormal base-line gallbladder sonograms. Thirty-six patients (ceftriaxone, n = 28; placebo, n = 8) demonstrated normal baseline gallbladder sonograms and were evaluated for the development of …

Effects Of Magnesium-Aluminum Hydroxide And Calcium Carbonate Antacids On Bioavailability Of Ofloxacin, Soledad Flor, David R. P. Guay, John A. Opsahl, Kenneth Tack, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The effects of 15- and 5-ml doses of magnesium-aluminum hydroxide (MAH) and calcium carbonate (CC) antacids, respectively, on the bioavailability of ofloxacin after single oral 400-mg doses of ofloxacin were investigated in a 32-subject, randomized, crossover, open-label study. On four separate occasions, subjects received ofloxacin alone or antacid 24 h before, 2 h before, or 2 h after ofloxacin administration (n = 16 for each antacid). CC administration had no significant effect on the rate and extent of ofloxacin absorption regardless of the timing of antacid administration. A small but significant negative effect of MAH administration 2 h before ofloxacin …