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MacLaren R.,Aurora Pharmaceutical | Reynolds P.M.,Aurora University | Allen R.R.,Peak Statistical Services
JAMA Internal Medicine | Year: 2014

IMPORTANCE Histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are commonly used to prevent gastrointestinal tract (GI) hemorrhage in critically ill patients. The stronger acid suppression of PPIs may reduce the rate of bleeding but enhance infectious complications, specifically pneumonia and Clostridium difficile infection (CDI). OBJECTIVE To evaluate the occurrence and risk factors for GI hemorrhage, pneumonia, and CDI in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS A pharmacoepidemiological cohort studywas conducted of adult patients requiring mechanical ventilation for 24 hours or more and administered either an H2RA or PPI for 48 hours or more while intubated across 71 hospitals between January 1, 2003, and December 31, 2008. Propensity score-adjusted and propensity-matched multivariate regression models were used to control for confounders. MAIN OUTCOMES AND MEASURES Primary outcomeswere secondary diagnoses of International Classification of Diseases, Ninth Revision (ICD-9)-coded GI hemorrhage, pneumonia, and CDI occurring 48 hours or more after initiating invasive ventilation. RESULTS Of 35 312 patients, 13 439 (38.1%) received H2RAs and 21 873 (61.9%) received PPIs. Gastrointestinal hemorrhage (2.1% vs 5.9%; P < .001), pneumonia (27%vs 38.6%; P < .001), and CDI (2.2%vs 3.8%; P < .001) occurred less frequently in the H2RA group. After adjusting for propensity score and covariates, odds ratios of GI hemorrhage (2.24; 95%CI, 1.81-2.76), pneumonia (1.2; 95%CI, 1.03-1.41), and CDI (1.29; 95%CI, 1.04-1.64) were greater with PPIs. Similar results were obtained in the propensity-matched models of 8799 patients in each cohort. CONCLUSIONS AND RELEVANCE Proton pump inhibitors are associated with greater risks of GI hemorrhage, pneumonia, and CDI than H2RAs in mechanically ventilated patients. Numerous other risk factors are apparent. These data warrant confirmation in comparative prospective studies. Copyright © 2014 American Medical Association. All rights reserved.


Kiser J.J.,Aurora Pharmaceutical | Burton J.R.,Aurora University | Everson G.T.,Aurora University
Nature Reviews Gastroenterology and Hepatology | Year: 2013

The emergence of direct-acting antiviral agents (DAAs) for HCV infection represents a major advance in treatment. The NS3 protease inhibitors, boceprevir and telaprevir, were the first DAAs to receive regulatory approval. When combined with PEG-IFN and ribavirin, these agents increase rates of sustained virologic response in HCV genotype 1 to ∼70%. However, this treatment regimen is associated with several toxicities. In addition, both boceprevir and telaprevir are substrates for and inhibitors of the drug transporter P-glycoprotein and the cytochrome P450 enzyme 3A4 and are, therefore, prone to clinically relevant drug interactions. Several new DAAs for HCV are in late stages of clinical development and are likely to be approved in the near future. These include the protease inhibitors, simeprevir and faldaprevir, the NS5A inhibitor, daclatasvir, and the nucleotide polymerase inhibitor, sofosbuvir. Herein, we review the clinical pharmacology and drug interactions of boceprevir, telaprevir and these investigational DAAs. Although boceprevir and telaprevir are involved in many interactions, these interactions are manageable if health-care providers proactively identify and adjust treatments. Emerging DAAs seem to have a reduced potential for drug interactions, which will facilitate their use in the treatment of HCV. © 2013 Macmillan Publishers Limited.


Maclaren R.,Aurora Pharmaceutical | Campbell J.,Aurora Pharmaceutical
Critical Care Medicine | Year: 2014

Objective: To examine the cost-effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Design: Decision analysis model examining costs and effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Costs were expressed in 2012 U.S. dollars from the perspective of the institution and included drug regimens and the following outcomes: clinically significant stress-related mucosal bleed, ventilator-associated pneumonia, and Clostridium difficile infection. Effectiveness was the mortality risk associated with these outcomes and represented by survival. Costs, occurrence rates, and mortality probabilities were extracted from published data. Setting: A simulation model. Patients: A mixed adult ICU population. Interventions: Histamine receptor-2 antagonist or proton pump inhibitor for 9 days of stress ulcer prophylaxis therapy. MAIN MEASUREMENTS AND RESULTS: Output variables were expected costs, expected survival rates, incremental cost, and incremental survival rate. Univariate sensitivity analyses were conducted to determine the drivers of incremental cost and incremental survival. Probabilistic sensitivity analysis was conducted using second-order Monte Carlo simulation. For the base case analysis, the expected cost of providing stress ulcer prophylaxis was $6,707 with histamine receptor-2 antagonist and $7,802 with proton pump inhibitor, resulting in a cost saving of $1,095 with histamine receptor-2 antagonist. The associated mortality probabilities were 3.819% and 3.825%, respectively, resulting in an absolute survival benefit of 0.006% with histamine receptor-2 antagonist. The primary drivers of incremental cost and survival were the assumptions surrounding ventilator-associated pneumonia and bleed. The probabilities that histamine receptor-2 antagonist was less costly and provided favorable survival were 89.4% and 55.7%, respectively. A secondary analysis assuming equal rates of C. difficile infection showed a cost saving of $908 with histamine receptor-2 antagonists, but the survival benefit of 0.0167% favored proton pump inhibitors. Conclusions: Histamine receptor-2 antagonist therapy appears to reduce costs with survival benefit comparable to proton pump inhibitor therapy for stress ulcer prophylaxis. Ventilator- associated pneumonia and bleed are the variables most affecting these outcomes. The uncertainty in the findings justifies a prospective trial. © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Smith S.M.,Aurora Pharmaceutical
Pharmacotherapy | Year: 2013

Resistant hypertension is a common clinical problem, which, until recently, has received little attention in the medical literature. With this increased attention has come a considerably better understanding of disease epidemiology, prognosis, and treatment, yet much remains unknown. Current data suggest that the prevalence of resistant hypertension has been increasing in recent decades, a concerning finding given that resistant hypertension appears to be associated with a poorer prognosis than nonresistant hypertension. The most appropriate management for these patients has not been fully elucidated, but a multifaceted approach incorporating accurate diagnosis, identification, and removal of substances that interfere with blood pressure, dietary and lifestyle management, and treatment with rational drug combination therapy can be quite effective in controlling blood pressure in these patients. Newer therapies, both pharmacologic and interventional procedures, are under study and may hold promise in the future treatment of resistant hypertension. This review highlights recent research on disease epidemiology and prognosis, and it describes the current body of literature on the treatment of this increasingly common condition. © 2013 Pharmacotherapy Publications, Inc.


Fritz K.S.,Aurora Pharmaceutical | Petersen D.R.,Aurora Pharmaceutical
Free Radical Biology and Medicine | Year: 2013

The nonenzymatic free radical generation of reactive aldehydes is known to contribute to diseases of sustained oxidative stress including rheumatoid arthritis, atherosclerosis, neurodegeneration, and a number of liver diseases. At the same time, the accumulation of lipid electrophiles has been demonstrated to play a role in cell signaling events through modification of proteins critical for cellular homeostasis. Given the broad scope of reactivity profiles and the ability to modify numerous proteomic and genomic processes, new emphasis is being placed on a systems-based analysis of the consequences of electrophilic adduction. This review focuses on the generation and chemical reactivity of lipid-derived aldehydes with a special focus on the homeostatic responses to electrophilic stress. © 2012 Elsevier Inc.


Petrash J.M.,Aurora Pharmaceutical
Investigative Ophthalmology and Visual Science | Year: 2013

Reduced quality of life and financial burden due to visual impairment and blindness begin to increase dramatically when individuals reach the age of 40. The major causes of agerelated vision loss can be traced to changes to the structure and function of the lens, one of the tissues responsible for focusing light on the retina. Age-related nuclear cataracts, which are caused by aggregation and condensation of proteins, diminish vision because they impede the transmission and focusing of light on the retina. In addition to the slowdeveloping age-related form, cataracts often develop rapidly as a complication of ocular surgery, such as following vitrectomy or as a consequence of vitreous gel degeneration. Posterior capsular opacification, which can develop following cataract removal, is caused by proliferation and inappropriate accumulation of lens epithelial cells on the surfaces of intraocular lenses and the posterior lens capsule. Presbyopia is a loss of accommodative amplitude and reduced ability to shift focus from far to near objects. Onset of presbyopia is associated with an increase in lens hardness and reduced ability of the lens to change shape in response to ciliary muscle contraction. Avenues of promising research that seek to delay or prevent these causes of low vision are discussed in light of our current understanding of disease pathogenesis and some challenges that must be met to achieve success. © The Association for Research in Vision and Ophthalmology, Inc.


Heit C.,Aurora Pharmaceutical
Sub-cellular biochemistry | Year: 2013

Ethanol consumption has effects on the central nervous system (CNS), manifesting as motor incoordination, sleep induction (hypnosis), anxiety, amnesia, and the reinforcement or aversion of alcohol consumption. Acetaldehyde (the direct metabolite of ethanol oxidation) contributes to many aspects of the behavioral effects of ethanol. Given acetaldehyde cannot pass through the blood brain barrier, its concentration in the CNS is primarily determined by local production from ethanol. Catalase and cytochrome P450 2E1 (CYP2E1) represent the major enzymes in the CNS that catalyze ethanol oxidation. CYP2E1 is expressed abundantly within the microsomes of certain brain cells and is localized to particular brain regions. This chapter focuses on the discussion of CYP2E1 in ethanol metabolism in the CNS, covering topics including how it is regulated, where it is expressed and how it influences sensitivity to ethanol in the brain.


Thompson A.M.,Aurora Pharmaceutical | Trujillo J.M.,Aurora Pharmaceutical
Annals of Pharmacotherapy | Year: 2015

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of the glucagon-like peptide-1 receptor agonist (GLP-1 RA), dulaglutide, in the treatment of type 2 diabetes mellitus (T2D). Data Sources: A PubMed search was completed to identify publications from 1947 to October 2014 using the search terms dulaglutide and LY2189265. References were reviewed to identify additional resources. Study Selection and Data Extraction: Articles were included if they evaluated the pharmacology, pharmacokinetics, safety, or efficacy of dulaglutide. Data Synthesis: Dulaglutide reduces both glycosylated hemoglobin (A1C) and weight by stimulating insulin secretion and suppressing glucagon in a glucose-dependent manner, delaying gastric emptying, and promoting satiety. Dulaglutide consists of 2 GLP-1 analogues that have been modified to make it a long-acting, once-weekly agent. Dulaglutide has been studied as monotherapy and in combination with metformin, glimepiride, pioglitazone, and insulin lispro. It has demonstrated superior A1C reduction compared with placebo, metformin, insulin glargine, sitagliptin, and twice-daily exenatide. It demonstrated noninferiority in A1C reduction to liraglutide. Dulaglutide changed A1C by −0.78% to −1.51%, and it changed weight by −0.35 kg to −3.03 kg. The most common adverse effects in clinical studies were nausea, vomiting, and diarrhea. Conclusions: Dulaglutide is the fifth GLP-1 RA approved for T2D in the United States. It is an attractive option because it is dosed once-weekly, provides A1C lowering similar to liraglutide, weight reduction similar to exenatide, and has an adverse effect profile similar to exenatide and liraglutide. © The Author(s) 2015


Patent
Aurora Pharmaceutical | Date: 2014-06-09

The present inventions relate to a number of fields including wound healing, a waterless antibacterial disinfectant, a surgical scrub, insect repellant, and methods of treating traumatic injuries, particularly those on the battlefield where there is a need to stabilize the patient and prevent infection.


Patent
Aurora Pharmaceutical | Date: 2014-03-18

This invention encompasses products and methods for preventing teat infections in cows resulting from a variety of causes. More specifically, this invention relates to products and methods for blocking a cows teat and teat canal to prevent infection during a non-lactating period.

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