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Stuart J Connolly, Truman J Milling, John W Eikelboom, C Michael Gibson, John T Curnutte, Alex Gold, Michele D Bronson, Genmin Lu, Pamela B Conley, Peter Verhamme, Jeannot Schmidt, Saskia Middeldorp, Alexander T Cohen, Jan Beyer-Westendorf, Pierre Albaladejo, Jose Lopez-Sendon, Shelly Goodman, Janet Leeds, Brian L Wiens, Deborah M Siegal, Elena Zotova, Brandi Meeks, Juliet Nakamya, W Ting Lim, Mark Crowther
Background Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. Methods In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period...
September 22, 2016: New England Journal of Medicine
Alexander T Cohen, Robert A Harrington, Samuel Z Goldhaber, Russell D Hull, Brian L Wiens, Alex Gold, Adrian F Hernandez, C Michael Gibson
BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days...
August 11, 2016: New England Journal of Medicine
Deborah M Siegal, John T Curnutte, Stuart J Connolly, Genmin Lu, Pamela B Conley, Brian L Wiens, Vandana S Mathur, Janice Castillo, Michele D Bronson, Janet M Leeds, Florie A Mar, Alex Gold, Mark A Crowther
BACKGROUND: Bleeding is a complication of treatment with factor Xa inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet is designed to reverse the anticoagulant effects of factor Xa inhibitors. METHODS: Healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily. For each factor Xa inhibitor, a two-part randomized placebo-controlled study was conducted to evaluate andexanet administered as a bolus or as a bolus plus a 2-hour infusion...
December 17, 2015: New England Journal of Medicine
Antonio Gomez-Outes, M L Suarez-Gea, Ramon Lecumberri, Ana I Terleira-Fernandez, Emilio Vargas-Castrillon
In the last decade, several direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) have been marketed for prophylaxis and/or treatment of thromboembolism without having specific antidotes available for their reversal. Current management of bleeding associated to DOAC includes the removal of all antithrombotic medications and supportive care. Non-specific procoagulant agents (prothrombin complex concentrates and activated factor VIIa) have been used in case of serious bleeding. Currently, some specific antidotes for the DOAC are under development...
2014: Recent Patents on Cardiovascular Drug Discovery
David Rosenberg, Ann Eichorn, Mauricio Alarcon, Lauren McCullagh, Alex Spyropoulos
SESSION TITLE: DVT/PE PostersSESSION TYPE: Poster PresentationsPRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PMPURPOSE: Current VTE prophylaxis guidelines strongly promote risk assessment on the individual level. The IMPROVE VTE risk assessment model (RAM) is a composite score formulated to predict individual VTE risk during hospitalization. It is developed from a derivation cohort and has preliminary validation. This score sums 7 risk factors into risk categories: 0-1-Low Risk, 2-3-Moderate risk, >=4-high risk...
March 1, 2014: Chest
Christopher Nessel, Kenneth Mahaffey, Jonathan Piccini, Guohua Pan, Manesh Patel, Richard Becker, Daniel Singer, Jonathan Halperin, Graeme Hankey, Scott Berkowitz, Keith Fox, Robert Califf
SESSION TYPE: Arrhythmia and Coronary Artery DiseasePRESENTED ON: Monday, October 22, 2012 at 11:15 AM - 12:30 PMPURPOSE: Gastrointestinal (GI) hemorrhage is a common complication of anticoagulant therapy. We investigated the incidence and outcomes of GI hemorrhage among patients in the ROCKET AF study.METHODS: In ROCKET AF, 14,264 patients with nonvalvular atrial fibrillation (AF) were randomized to rivaroxaban or dose-adjusted warfarin. This post hoc analysis was performed on all patients while receiving study medication until two days after the last dose, using adjudicated data from the blinded, independent clinical events committee...
October 1, 2012: Chest
Ajay Yadlapati, Tristan Grogan, David Elashoff, Robert B Kelly
Using a novel noninvasive, visible-light optical diffusion oximeter (T-Stat VLS Tissue Oximeter; Spectros Corporation, Portola Valley, CA) to measure the tissue oxygen saturation (StO2) of the buccal mucosa, the correlation between StOz and central venous oxygen saturation (ScvO2) was examined in children with congenital cyanotic heart disease undergoing a cardiac surgical procedure. Paired StO2 and serum ScvO2 measurements were obtained postoperatively and statistically analyzed for agreement and association...
March 2013: Journal of Extra-corporeal Technology
Martice E Vasquez, Janna Rinderneck, Julie Newman, Stella McMillin, Brian Finlayson, Abdou Mekebri, David Crane, Ronald S Tjeerdema
In September 2007, Lake Davis (near Portola, California) was treated by the California Department of Fish and Game with CFT Legumine, a rotenone formulation, to eradicate the invasive northern pike (Esox lucius). The objective of this report is to describe the fate of the five major formulation constituents-rotenone, rotenolone, methyl pyrrolidone (MP), diethylene glycol monethyl ether (DEGEE), and Fennedefo 99-in water, sediment, and brown bullhead catfish (Ameiurus nebulosus; a rotenone-resistant species) by determination of their half-lives (t(1/2)) and pseudo first-order dissipation rate constants (k)...
May 2012: Environmental Toxicology and Chemistry
Alessandro F Moretto, Christoph Dehnhardt, Neelu Kaila, Nikolaos Papaioannou, Atli Thorarensen
Discovery of small molecular inhibitors for treatment of rheumatoid arthritis is a major ongoing effort within the pharmaceutical industry. Spleen tyrosine kinase (SYK) is one of leading small molecular targets with regard to clinical development primarlly due to efforts by Rigel and Portola. In this review, we provide a comprehensive overview of the SYK patent landscape. The patent literature we evaluated relates to any organization that has filed applications that imply that SYK is the intended target. The interest in SYK was initiated in the early 2000's with many organizations, including several large pharmaceutical companies, and has been active for years...
May 2012: Recent Patents on Inflammation & Allergy Drug Discovery
William J Moore, David Richard, Atli Thorarensen
IMPORTANCE OF THE FIELD: Discovery of small molecule inhibitors for treatment of rheumatoid arthritis is a major ongoing effort within the pharmaceutical industry. Spleen tyrosine kinase (SYK) is one of the leading small molecular targets with regard to clinical developments due to the efforts of Rigel and Portola. AREAS COVERED IN THIS REVIEW: Diaminopyrimidines are one of the most prominent structural elements incorporated into the design of kinase inhibitors...
December 2010: Expert Opinion on Therapeutic Patents
Julie H Oestreich
P2Y purinergic receptor subtypes are expressed on the surface of platelets and are vitally important for platelet function. Elinogrel (PRT-060128), a novel, direct-acting and reversible platelet P2Y12 receptor (P2Y12R) antagonist, is being developed by Portola Pharmaceuticals Inc and Novartis AG for the intravenous and oral treatment of acute coronary syndrome and prevention of secondary thrombotic events. In phase I clinical trials, elinogrel demonstrated a rapid and potent inhibition of ADP-mediated platelet response, even in patients with coronary artery disease who were deemed non-responsive to clopidogrel, the current standard-of-care therapy...
March 2010: Current Opinion in Investigational Drugs
Olga Portolá, Ramón Guitart, Frederic Gómez, Montserrat Olona, Francesc Vidal, Antoni Castro et al.
INTRODUCTION: Nocardia infections are uncommon, and the clinical experience with this pathogen is limited. METHODS: We describe the clinical characteristics of a series of 22 patients (17 men) with Nocardia infection seen between 1997 and 2008. RESULTS: Mean age was 63.2+/-19.2 years. The most common clinical forms observed were lower respiratory tract infection (15/22, 68%, 8 bronchitis and 7 pneumonia) mainly in patients with chronic obstructive pulmonary disease (10/22, 45%), and skin involvement (4/22, 19%)...
December 2009: Enfermedades Infecciosas y Microbiología Clínica
Eugene S Lee, William C Pevec, Daniel P Link, David L Dawson
As surgeons become more aggressive in treating aneurysms with endovascular techniques, traditional surgical principles of preserving internal iliac arteries and the inferior mesenteric artery have been challenged. A case is presented where the T-Stat device (Spectros Corp, Portola Valley, Calif), an optical real-time sensor approved by United States Food and Drug Administration for measuring colon ischemia, was used as an adjunctive measure to assist in the successful endovascular aneurysm repair in a patient at high risk for colon ischemia...
March 2008: Journal of Vascular Surgery
Shai Friedland, David Benaron, Sheila Coogan, Daniel Y Sze, Roy Soetikno
BACKGROUND: Chronic mesenteric ischemia can be difficult to diagnose by means of currently available clinical techniques. We developed a novel endoscopic device for objective measurement of GI mucosal ischemia. OBJECTIVE: Our purpose was to evaluate the performance of the device in patients with chronic mesenteric ischemia. DESIGN: A fiberoptic catheter-based visible light spectroscopy oximeter (T-Stat 303 Microvascular Oximeter, Spectros, Portola Valley, Calif) was used to evaluate 30 healthy control subjects and 3 patients with chronic mesenteric ischemia before and after successful percutaneous stenting...
February 2007: Gastrointestinal Endoscopy
Chris Dalziel
No abstract text is available yet for this article.
March 2006: IDrugs: the Investigational Drugs Journal
Eddine Saiah, Chris Soares
Venous thromboembolic disease, including deep vein thrombosis and pulmonary embolism, is a cause of significant mortality and morbidity. For several decades, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. A variety of novel anticoagulants with improved pharmacologic and clinical profiles are in development, offering benefits over traditional therapies...
2005: Current Topics in Medicinal Chemistry
B B Lothrop, M S Mulla
A series of experiments was carried out in a 0.5-ha lake at Portola Country Club, Palm Desert, CA, to study the oviposition habits of Chironomus anonymus. Egg masses were collected by floatable polypropylene ropes attached to the 1.5-m-long stakes placed in the lake. In the diel experiment, ropes were changed every 2 h to determine the preferred oviposit on periods of C. anonymus. The peak of oviposition was between 1900 and 2100 h. For the interruption of oviposition experiment, ropes were placed in the still and agitated portions of the lake for 24 h...
June 1996: Journal of the American Mosquito Control Association
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