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25 papers 500 to 1000 followers LoL. Tamiflu may need a new indication.Questioning Medicine previous podcast #FOAMed #MedQuestioning
By Joe Weatherly FM/Hospitalist-CoFounder of QuestioningMedicine and PCRAP contributor.
Joanna Dobson, Richard J Whitley, Stuart Pocock, Arnold S Monto
BACKGROUND: Despite widespread use, questions remain about the efficacy of oseltamivir in the treatment of influenza. We aimed to do an individual patient data meta-analysis for all clinical trials comparing oseltamivir with placebo for treatment of seasonal influenza in adults regarding symptom alleviation, complications, and safety. METHODS: We included all published and unpublished Roche-sponsored randomised placebo-controlled, double-blind trials of 75 mg twice a day oseltamivir in adults...
May 2, 2015: Lancet
Alexandre V Ivachtchenko, Yan A Ivanenkov, Oleg D Mitkin, Pavel M Yamanushkin, Vadim V Bichko, Natalia A Shevkun, Olga V Mokrushina, Olga O Nevolina, Ruben N Karapetian, Irina A Leneva, Irina T Fedyakina, Mark S Veselov
OBJECTIVES: Development of a novel drug candidate with improved activity against influenza virus neuraminidase (NA) compared with currently available therapeutics. METHODS: Synthesized compounds were evaluated in vitro and in vivo. Three-dimensional molecular docking was successfully applied to classify compounds within the series by inhibitory potency. Stability was investigated in blood samples and in animal models. A pharmacokinetic study was performed in dogs and rats using peroral and intravenous administration...
May 2014: Journal of Antimicrobial Chemotherapy
Masatoki Sato, Ken Honzumi, Toshiko Sato, Koichi Hashimoto, Masahiro Watanabe, Kyohei Miyazaki, Yukihiko Kawasaki, Mitsuaki Hosoya
BACKGROUND: The objective of this study was to estimate the efficacy of the neuraminidase (NA) inhibitors (NAIs) oseltamivir and zanamivir for decreasing viral load and to investigate whether NAI treatment decreases viral susceptibility to NAIs over time in children with influenza B virus infection. METHODS: Of 27 patients with influenza B virus infection, 8 and 9 were treated with oseltamivir and zanamivir, respectively, whereas 10 received no NAI. Nasal aspiration samples, collected every morning until negative antigen results in 2 consecutive samples were observed, were subjected to viral load measurements by quantitative real-time reverse transcription polymerase chain reaction and viral susceptibility to NAI by NA inhibition assays...
July 2014: Pediatric Infectious Disease Journal
Arnab Basu, Aleksandar Antanasijevic, Minxiu Wang, Bing Li, Debra M Mills, Jessica A Ames, Peter J Nash, John D Williams, Norton P Peet, Donald T Moir, Mark N Prichard, Kathy A Keith, Dale L Barnard, Michael Caffrey, Lijun Rong, Terry L Bowlin
Influenza viruses are a major public health threat worldwide, and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. The influenza virus glycoprotein hemagglutinin (HA) plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a potential target for the development of anti-influenza drugs. Using pseudotype virus-based high-throughput screens, we have identified several new small molecules capable of inhibiting influenza virus entry...
February 2014: Journal of Virology
Evelien Vanderlinden, Lieve Naesens
Influenza A and B viruses are highly contagious respiratory pathogens with a considerable medical and socioeconomical burden and known pandemic potential. Current influenza vaccines require annual updating and provide only partial protection in some risk groups. Due to the global spread of viruses with resistance to the M2 proton channel inhibitor amantadine or the neuraminidase inhibitor oseltamivir, novel antiviral agents with an original mode of action are urgently needed. We here focus on emerging options to interfere with the influenza virus entry process, which consists of the following steps: attachment of the viral hemagglutinin to the sialylated host cell receptors, endocytosis, M2-mediated uncoating, low pH-induced membrane fusion, and, finally, import of the viral ribonucleoprotein into the nucleus...
March 2014: Medicinal Research Reviews
Diego Viasus, José Ramón Paño-Pardo, Jerónimo Pachón, Melchor Riera, Francisco López-Medrano, Antoni Payeras, M Carmen Fariñas, Asunción Moreno, Jesús Rodríguez-Baño, José Antonio Oteo, Lucia Ortega, Julián Torre-Cisneros, Ferrán Segura, Jordi Carratalà
BACKGROUND: Data on the clinical effectiveness of oseltamivir in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) virus infection are scarce. We aimed to determine the effect of timing of oseltamivir administration on outcomes in hospitalized adults with A(H1N1). METHODS: Observational analysis of a prospective cohort of adults hospitalized with laboratory-confirmed A(H1N1) was performed at 13 Spanish hospitals. Time from onset of symptoms to oseltamivir administration was the independent variable...
October 2011: Chest
Mohamed A Kamal, Scott A Van Wart, Craig R Rayner, Vishak Subramoney, Daniel K Reynolds, Catharine C Bulik, Patrick F Smith, Sujata M Bhavnani, Paul G Ambrose, Alan Forrest
Oseltamivir is a potent inhibitor of influenza virus neuraminidase enzymes essential for viral replication. This study aimed to investigate the impact of covariates on pharmacokinetic (PK) variability of oseltamivir and its active metabolite form, oseltamivir carboxylate (OC). Dosing history, plasma drug concentrations, and demographic information were pooled from 13 clinical trials providing data for 390 healthy and infected subjects ranging in age from 1 to 78 years and given oseltamivir doses of 20 to 1,000 mg...
August 2013: Antimicrobial Agents and Chemotherapy
N Lee, D S C Hui, Z Zuo, K L K Ngai, G C Y Lui, S K Wo, W W S Tam, M C W Chan, B C K Wong, R Y K Wong, K W Choi, W W Y Sin, E L Y Lee, B Tomlinson, F G Hayden, P K S Chan
BACKGROUND: It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. METHODS: A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons...
December 2013: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Alicia M Fry, Doli Goswami, Kamrun Nahar, Amina Tahia Sharmin, Mustafizur Rahman, Larisa Gubareva, Tasnim Azim, Joseph Bresee, Stephen P Luby, W Abdullah Brooks
BACKGROUND: Influenza causes substantial morbidity and mortality worldwide. Few data exist for the efficacy of neuraminidase inhibitors, which are the only readily available influenza treatment options, especially in low-income settings. We assessed the efficacy of treatment with the neuraminidase inhibitor oseltamivir to reduce patient illness and viral shedding in people with influenza, in whom treatment was started within 5 days of symptom onset, in an urban setting in Bangladesh. METHODS: We undertook a double-blind, randomised, controlled trial between May, 2008, and December, 2010...
February 2014: Lancet Infectious Diseases
Nila J Dharan, Larisa V Gubareva, John J Meyer, Margaret Okomo-Adhiambo, Reginald C McClinton, Steven A Marshall, Kirsten St George, Scott Epperson, Lynnette Brammer, Alexander I Klimov, Joseph S Bresee, Alicia M Fry
CONTEXT: During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season. OBJECTIVES: To describe patients infected with oseltamivir-resistant influenza A(H1N1) virus and to determine whether there were any differences between these patients and patients infected with oseltamivir-susceptible A(H1N1) virus in demographic or epidemiological characteristics, clinical symptoms, severity of illness, or clinical outcomes...
March 11, 2009: JAMA: the Journal of the American Medical Association
R Welliver, A S Monto, O Carewicz, E Schatteman, M Hassman, J Hedrick, H C Jackson, L Huson, P Ward, J S Oxford
CONTEXT: Influenza virus is easily spread among the household contacts of an infected person, and prevention of influenza in household contacts can control spread of influenza in the community. OBJECTIVE: To investigate the efficacy of oseltamivir in preventing spread of influenza to household contacts of influenza-infected index cases (ICs). DESIGN AND SETTING: Randomized, double-blind, placebo-controlled study conducted at 76 centers in North America and Europe during the winter of 1998-1999...
February 14, 2001: JAMA: the Journal of the American Medical Association
Panče Naumov, Nobuhiro Yasuda, Wael M Rabeh, Joel Bernstein
The first structure determination of a neuraminidase inhibitor, oseltamivir phosphate, the active component of the anti-influenza agent Tamiflu, was achieved by single crystal X-ray diffraction with synchrotron radiation. The structure reproduces to a great extent the binding of the inhibitor in the neuraminidase active site and provides more accurate structural parameters as well as detailed insight into the binding preferences of the inhibitor.
March 7, 2013: Chemical Communications: Chem Comm
Ly Le, Eric H Lee, David J Hardy, Thanh N Truong, Klaus Schulten
Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus. Unfortunately, how mutations actually confer drug resistance is not well understood. In this study, we employ molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, as well as graphics processing unit (GPU)-accelerated electrostatic mapping, to uncover the mechanism behind point mutation induced oseltamivir-resistance in both H5N1 "avian" and H1N1pdm "swine" flu N1-subtype neuraminidases...
September 23, 2010: PLoS Computational Biology
Wei-Yu Chen, Chia-Jung Lin, Chung-Min Liao
Environmental pollution by anti-influenza drugs is increasingly recognized as a threat to aquatic environments. However, little is known about empirical data on risk effects posed by environmentally relevant concentrations of anti-influenza drug based on recently published ecotoxicological researches in Taiwan. Here we linked ecotoxicology models with an epidemiological scheme to assess exposure risks of aquatic organisms and environmental hazards posed by antiviral oseltamivir (Tamiflu) use in Taiwan. Built on published bioassays, we used probabilistic risk assessment model to estimate potential threats of environmentally relevant hazards on algae, daphnid, and zerbrafish...
January 2014: Environmental Pollution
Peter C Gøtzsche
No abstract text is available yet for this article.
May 15, 2013: BMJ: British Medical Journal
L V Kolobukhina, L N Merkulova, E I Burtseva, E I Isaeva, M Iu Shchelkanov, N V Beliakova, T V Grebennikova, O E Polikushina, M Rotanov, N A Malyshev, D K L'vov
The paper gives the results of using ozeltamivir in patients with influenza during the epidemic upsurge of morbidity in Russia in the 2006-2007 season. Comparative analysis of nucteotide sequences of viral strains isolated from the patients taking ozeltamivir revealed no marker mutations determining the resistance to this chemical.
July 2008: Voprosy Virusologii
Christopher Ellis, Ruth McEwen
No abstract text is available yet for this article.
July 6, 2009: BMJ: British Medical Journal
Deborah Cohen
No abstract text is available yet for this article.
April 4, 2013: BMJ: British Medical Journal
Fiona Godlee
No abstract text is available yet for this article.
December 12, 2012: BMJ: British Medical Journal
Harlan M Krumholz, Cynthia A Jackevicius, Joseph S Ross
No abstract text is available yet for this article.
January 25, 2013: BMJ: British Medical Journal
2014-02-12 04:38:38
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